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Sharon Worcester is an award-winning medical journalist for MDedge News. She has been with the company since 1996, first as the Southeast Bureau Chief (1996-2009) when the company was known as International Medical News Group, then as a freelance writer (2010-2015) before returning as a reporter in 2015. She previously worked as a daily newspaper reporter covering health and local government. Sharon currently reports primarily on oncology and hematology. She has a BA from Eckerd College and an MA in Mass Communication/Print Journalism from the University of Florida. Connect with her via LinkedIn and follow her on twitter @SW_MedReporter.
CML: Select TKI based on comorbidities, monitor toxicity and adherence
CHICAGO – Chronic myeloid leukemia is highly treatable, and a “functional cure” appears to be within reach, according to Dr. Michael J. Mauro.
In fact, an “embarrassment of riches” exists when it comes to initial therapy for CML: In the United States there are five approved tyrosine kinase inhibitors (TKIs), and three are approved for front-line therapy, Dr. Mauro of Memorial Sloan Kettering Cancer Center, New York, said at the American Society of Hematology Meeting on Hematologic Malignancies.
Success, however, is contingent on managing reversible early toxicity, adherence to therapy, achieving landmarks of response, and remaining vigilant for late effects of therapy, he said.
Given the multitude of treatment options and the breadth of available data, Dr. Mauro said he counsels newly diagnosed patients that various treatment options are valid, and that “there may not be a right or wrong answer” for initial therapy. He also counsels patients that tolerability is manageable – and finding the right fit is an important process, and that response milestones are crucial and should be optimized.
It is important, he said, to discuss late toxicity concerns, to review comorbid conditions to help predict potential problems and identify risk, to consider the ramifications of potential toxicity, and to consider adherence.
“We need to portray therapy as really being medium- to long-term,” he said, noting that the urgency to think about treatment-free remission should be tempered by the reality that years of treatment are required first.
Risks and benefits of treatment should be discussed, and the acceptable balance determined in conjunction with the patient, he said, explaining that toxicities vary for the different TKIs.
Imatinib, for example, can be associated with edema/fluid retention, myalgias, hypophosphatemia, and gastrointestinal effects. Dasatinib can be associated with pleural/pericardial effusion, pulmonary arterial hypertension, and bleeding risk. Other toxicities associated with certain TKIs include pancreatic enzyme elevation, rash, and vascular adverse events.
Whether newly diagnosed patients should be directed away from certain agents remains unclear, as available data are open to interpretation, and the mechanism of action for some crucial late effects is unknown. Vascular disease should, however, be considered when making the decision, he said.
Given the available data on late toxicity with various therapies, a cardiovascular evaluation is advisable when initiating TKI therapy, he added.
Consider partnering with primary care, cardiology, or cardio-oncology specialists, and manage risk factors and findings of the evaluation as appropriate, irrespective of the CML, he said. Monitor for progression of cardiovascular risks or adverse events carefully, he added.
His approach for following recently diagnosed CML patients involves:
• A cardiovascular evaluation, at least including age- and comorbidity-appropriate studies, and an up-to-date cardiovascular risk profile. If nilotinib is used, he screens for peripheral, cerebral, and cardiovascular disease – an approach increasingly supported by data. If dasatinib is used, echocardiography is warranted to look for changes that suggest pulmonary hypertension. “And of course we should monitor blood pressure, lipid, and glycemic control,” he added.
• Initial studies, including bone marrow and quantitative polymerase chain reaction – international scale (qPCR IS).
• Lab studies every 1-2 weeks for at least 6 weeks, with titration thereafter as indicated, including for change in therapy.
• A 3-month assessment using qPCR IS. This is very important for following patient response, he said, noting that if the response surpasses compete cytogenetic remission and blood count is acceptable and stable, a repeat bone marrow study may be unnecessary.
• Sequential molecular analyses at least every 3 months.
• Repeat cardiovascular evaluation if/when indicated.
The 3-month response is an opportunity to critically appraise therapy choice and response trajectory; a therapy change is possible based on this assessment, he said. Responses at 6 and 12 months are also important, and changes in therapy for missed milestones at these time points are warranted as deeper remissions are sought.
At 18 months, the focus is on major molecular response, he added, noting that as patients get into deeper molecular remissions, plateaus and fluctuations are common; the nuances of determining who is well enough to consider for treatment-free remission remain to be sorted out in clinical trials.
In general, it appears that 3 years of therapy with about 2 years of optimal minimal residual disease is required prior to consideration for treatment-free remission, he said.
Dr. Mauro has consulted for and/or received research funding from Ariad, Bristol-Myers Squibb, Novartis, and Oregon Health & Science University.
CHICAGO – Chronic myeloid leukemia is highly treatable, and a “functional cure” appears to be within reach, according to Dr. Michael J. Mauro.
In fact, an “embarrassment of riches” exists when it comes to initial therapy for CML: In the United States there are five approved tyrosine kinase inhibitors (TKIs), and three are approved for front-line therapy, Dr. Mauro of Memorial Sloan Kettering Cancer Center, New York, said at the American Society of Hematology Meeting on Hematologic Malignancies.
Success, however, is contingent on managing reversible early toxicity, adherence to therapy, achieving landmarks of response, and remaining vigilant for late effects of therapy, he said.
Given the multitude of treatment options and the breadth of available data, Dr. Mauro said he counsels newly diagnosed patients that various treatment options are valid, and that “there may not be a right or wrong answer” for initial therapy. He also counsels patients that tolerability is manageable – and finding the right fit is an important process, and that response milestones are crucial and should be optimized.
It is important, he said, to discuss late toxicity concerns, to review comorbid conditions to help predict potential problems and identify risk, to consider the ramifications of potential toxicity, and to consider adherence.
“We need to portray therapy as really being medium- to long-term,” he said, noting that the urgency to think about treatment-free remission should be tempered by the reality that years of treatment are required first.
Risks and benefits of treatment should be discussed, and the acceptable balance determined in conjunction with the patient, he said, explaining that toxicities vary for the different TKIs.
Imatinib, for example, can be associated with edema/fluid retention, myalgias, hypophosphatemia, and gastrointestinal effects. Dasatinib can be associated with pleural/pericardial effusion, pulmonary arterial hypertension, and bleeding risk. Other toxicities associated with certain TKIs include pancreatic enzyme elevation, rash, and vascular adverse events.
Whether newly diagnosed patients should be directed away from certain agents remains unclear, as available data are open to interpretation, and the mechanism of action for some crucial late effects is unknown. Vascular disease should, however, be considered when making the decision, he said.
Given the available data on late toxicity with various therapies, a cardiovascular evaluation is advisable when initiating TKI therapy, he added.
Consider partnering with primary care, cardiology, or cardio-oncology specialists, and manage risk factors and findings of the evaluation as appropriate, irrespective of the CML, he said. Monitor for progression of cardiovascular risks or adverse events carefully, he added.
His approach for following recently diagnosed CML patients involves:
• A cardiovascular evaluation, at least including age- and comorbidity-appropriate studies, and an up-to-date cardiovascular risk profile. If nilotinib is used, he screens for peripheral, cerebral, and cardiovascular disease – an approach increasingly supported by data. If dasatinib is used, echocardiography is warranted to look for changes that suggest pulmonary hypertension. “And of course we should monitor blood pressure, lipid, and glycemic control,” he added.
• Initial studies, including bone marrow and quantitative polymerase chain reaction – international scale (qPCR IS).
• Lab studies every 1-2 weeks for at least 6 weeks, with titration thereafter as indicated, including for change in therapy.
• A 3-month assessment using qPCR IS. This is very important for following patient response, he said, noting that if the response surpasses compete cytogenetic remission and blood count is acceptable and stable, a repeat bone marrow study may be unnecessary.
• Sequential molecular analyses at least every 3 months.
• Repeat cardiovascular evaluation if/when indicated.
The 3-month response is an opportunity to critically appraise therapy choice and response trajectory; a therapy change is possible based on this assessment, he said. Responses at 6 and 12 months are also important, and changes in therapy for missed milestones at these time points are warranted as deeper remissions are sought.
At 18 months, the focus is on major molecular response, he added, noting that as patients get into deeper molecular remissions, plateaus and fluctuations are common; the nuances of determining who is well enough to consider for treatment-free remission remain to be sorted out in clinical trials.
In general, it appears that 3 years of therapy with about 2 years of optimal minimal residual disease is required prior to consideration for treatment-free remission, he said.
Dr. Mauro has consulted for and/or received research funding from Ariad, Bristol-Myers Squibb, Novartis, and Oregon Health & Science University.
CHICAGO – Chronic myeloid leukemia is highly treatable, and a “functional cure” appears to be within reach, according to Dr. Michael J. Mauro.
In fact, an “embarrassment of riches” exists when it comes to initial therapy for CML: In the United States there are five approved tyrosine kinase inhibitors (TKIs), and three are approved for front-line therapy, Dr. Mauro of Memorial Sloan Kettering Cancer Center, New York, said at the American Society of Hematology Meeting on Hematologic Malignancies.
Success, however, is contingent on managing reversible early toxicity, adherence to therapy, achieving landmarks of response, and remaining vigilant for late effects of therapy, he said.
Given the multitude of treatment options and the breadth of available data, Dr. Mauro said he counsels newly diagnosed patients that various treatment options are valid, and that “there may not be a right or wrong answer” for initial therapy. He also counsels patients that tolerability is manageable – and finding the right fit is an important process, and that response milestones are crucial and should be optimized.
It is important, he said, to discuss late toxicity concerns, to review comorbid conditions to help predict potential problems and identify risk, to consider the ramifications of potential toxicity, and to consider adherence.
“We need to portray therapy as really being medium- to long-term,” he said, noting that the urgency to think about treatment-free remission should be tempered by the reality that years of treatment are required first.
Risks and benefits of treatment should be discussed, and the acceptable balance determined in conjunction with the patient, he said, explaining that toxicities vary for the different TKIs.
Imatinib, for example, can be associated with edema/fluid retention, myalgias, hypophosphatemia, and gastrointestinal effects. Dasatinib can be associated with pleural/pericardial effusion, pulmonary arterial hypertension, and bleeding risk. Other toxicities associated with certain TKIs include pancreatic enzyme elevation, rash, and vascular adverse events.
Whether newly diagnosed patients should be directed away from certain agents remains unclear, as available data are open to interpretation, and the mechanism of action for some crucial late effects is unknown. Vascular disease should, however, be considered when making the decision, he said.
Given the available data on late toxicity with various therapies, a cardiovascular evaluation is advisable when initiating TKI therapy, he added.
Consider partnering with primary care, cardiology, or cardio-oncology specialists, and manage risk factors and findings of the evaluation as appropriate, irrespective of the CML, he said. Monitor for progression of cardiovascular risks or adverse events carefully, he added.
His approach for following recently diagnosed CML patients involves:
• A cardiovascular evaluation, at least including age- and comorbidity-appropriate studies, and an up-to-date cardiovascular risk profile. If nilotinib is used, he screens for peripheral, cerebral, and cardiovascular disease – an approach increasingly supported by data. If dasatinib is used, echocardiography is warranted to look for changes that suggest pulmonary hypertension. “And of course we should monitor blood pressure, lipid, and glycemic control,” he added.
• Initial studies, including bone marrow and quantitative polymerase chain reaction – international scale (qPCR IS).
• Lab studies every 1-2 weeks for at least 6 weeks, with titration thereafter as indicated, including for change in therapy.
• A 3-month assessment using qPCR IS. This is very important for following patient response, he said, noting that if the response surpasses compete cytogenetic remission and blood count is acceptable and stable, a repeat bone marrow study may be unnecessary.
• Sequential molecular analyses at least every 3 months.
• Repeat cardiovascular evaluation if/when indicated.
The 3-month response is an opportunity to critically appraise therapy choice and response trajectory; a therapy change is possible based on this assessment, he said. Responses at 6 and 12 months are also important, and changes in therapy for missed milestones at these time points are warranted as deeper remissions are sought.
At 18 months, the focus is on major molecular response, he added, noting that as patients get into deeper molecular remissions, plateaus and fluctuations are common; the nuances of determining who is well enough to consider for treatment-free remission remain to be sorted out in clinical trials.
In general, it appears that 3 years of therapy with about 2 years of optimal minimal residual disease is required prior to consideration for treatment-free remission, he said.
Dr. Mauro has consulted for and/or received research funding from Ariad, Bristol-Myers Squibb, Novartis, and Oregon Health & Science University.
EXPERT ANALYSIS FROM MHM 2015
TCT: FFR-CT improved costs, quality of life in PLATFORM trial
SAN FRANCISCO – Estimating fractional flow reserve with computed tomography appears to reduce resource use and costs when compared with invasive coronary angiography in stable patients with possible symptoms of coronary disease, according to a substudy of the prospective, multicenter PLATFORM trial.
Fractional flow reserve estimated by CT (FFR-CT) was also associated with greater improvement in quality of life measures during the 90-day study period, when compared with usual noninvasive testing, Dr. Mark A. Hlatky of Stanford (Calif.) University reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
The PLATFORM trial and substudy data are “game changers,” according to the discussant, Dr. Bernard de Bruyne of Cardiovascular Center Aalst, Belgium, who predicted that if the findings are confirmed in other studies, “this kind of approach will probably largely replace the presently available noninvasive approaches and noninvasive stress testing.”
To assess the effect of using FFR-CT rather than usual care on cost and quality of life, patients with stable symptoms, intermediate probability of CAD (the pretest CAD probability was 49%), and no established CAD diagnosis were enrolled into one of two strata based on whether invasive or noninvasive diagnostic testing was planned. Among 193 patients in the planned invasive testing group who underwent FFR-CT, costs were reduced by 32%, compared with 187 patients in the group who received usual care ($7,343 vs. $10,734). The difference was highly statistically significant.
Among 104 patients in the planned noninvasive testing group who underwent FFR-CT, costs did not differ significantly, compared with 100 in that group who received usual care ($2,679 vs. $2,137), Dr. Hlatky reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.
These findings persisted after propensity score matching, he noted.
Furthermore, scores on each of three quality of life measures improved in the overall study population, and scores in the noninvasive stratum improved more with FFR-CT than with usual care. For example, Seattle Angina Questionnaire scores were 19.5 vs. 11.4, EuroQOL scores were 0.08 vs. 0.03, and visual analog scale scores were 4.1 vs. 2.3 in the groups, respectively. The improvements in the invasive cohort were similar with FFR-CT and usual care, Dr. Hlatky noted.
The findings, published simultaneously online (J Am Coll Cardiol. 2015. doi:10.1016/j.jacc.2015.09.051), suggest that the combination of anatomic and functional data provided by an FFR-CT–guided testing strategy may lead to more selective use of invasive procedures than relying solely on the anatomic data provided by invasive coronary angiography, Dr. Hlatky reported.
He explained that FFR, which assesses the functional significance of individual coronary lesions, can be estimated noninvasively from standardly acquired CT data based on computational fluid dynamics. FFR-CT was recently approved for clinical use by the Food and Drug Administration and the European Medicines Agency based on its diagnostic accuracy, he said.
The clinical effectiveness of the strategy was demonstrated in the PLATFORM trial which showed a reduction in the rate of invasive angiography without obstructive coronary artery disease from 73% to 12% with the use of FFR-CT. The current findings further demonstrate that the approach improves quality of life outcomes.
Though limited by the use of a consecutive observational design, as opposed to a randomized trial design, the large effect sizes suggest that findings would be similar in a randomized study, Dr. Hlatky said.
“I don’t think this is by chance. The plausibility of it has been explained,” he said, adding that while most people are happy with a normal CT angiography because of the high sensitivity, estimated FFR using the CT technique can be helpful in the setting of uncertainty.
“If you see something and you’re not sure if it’s significant, and if the estimated FFR from this technique is normal, that’s extremely reassuring that it’s just something you’re seeing but it’s not necessarily obstructing flow,” he said.
He added that “this would be best tested by doing a real, true, randomized study,” but said he considers the findings to be “quite interesting and completely in line with the clinical results.”
The technique is “entering progressively into practice in Europe,” said Dr. de Bruyne, who is a PLATFORM coinvestigator. “It is already used in clinical practice. You get the anatomy and physiology at the same time and same place. It is a really important paradigm change,” he said.
Dr. Hlatky and Dr. de Bruyne reported receiving research grants from HeartFlow, which supported the study.
SAN FRANCISCO – Estimating fractional flow reserve with computed tomography appears to reduce resource use and costs when compared with invasive coronary angiography in stable patients with possible symptoms of coronary disease, according to a substudy of the prospective, multicenter PLATFORM trial.
Fractional flow reserve estimated by CT (FFR-CT) was also associated with greater improvement in quality of life measures during the 90-day study period, when compared with usual noninvasive testing, Dr. Mark A. Hlatky of Stanford (Calif.) University reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
The PLATFORM trial and substudy data are “game changers,” according to the discussant, Dr. Bernard de Bruyne of Cardiovascular Center Aalst, Belgium, who predicted that if the findings are confirmed in other studies, “this kind of approach will probably largely replace the presently available noninvasive approaches and noninvasive stress testing.”
To assess the effect of using FFR-CT rather than usual care on cost and quality of life, patients with stable symptoms, intermediate probability of CAD (the pretest CAD probability was 49%), and no established CAD diagnosis were enrolled into one of two strata based on whether invasive or noninvasive diagnostic testing was planned. Among 193 patients in the planned invasive testing group who underwent FFR-CT, costs were reduced by 32%, compared with 187 patients in the group who received usual care ($7,343 vs. $10,734). The difference was highly statistically significant.
Among 104 patients in the planned noninvasive testing group who underwent FFR-CT, costs did not differ significantly, compared with 100 in that group who received usual care ($2,679 vs. $2,137), Dr. Hlatky reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.
These findings persisted after propensity score matching, he noted.
Furthermore, scores on each of three quality of life measures improved in the overall study population, and scores in the noninvasive stratum improved more with FFR-CT than with usual care. For example, Seattle Angina Questionnaire scores were 19.5 vs. 11.4, EuroQOL scores were 0.08 vs. 0.03, and visual analog scale scores were 4.1 vs. 2.3 in the groups, respectively. The improvements in the invasive cohort were similar with FFR-CT and usual care, Dr. Hlatky noted.
The findings, published simultaneously online (J Am Coll Cardiol. 2015. doi:10.1016/j.jacc.2015.09.051), suggest that the combination of anatomic and functional data provided by an FFR-CT–guided testing strategy may lead to more selective use of invasive procedures than relying solely on the anatomic data provided by invasive coronary angiography, Dr. Hlatky reported.
He explained that FFR, which assesses the functional significance of individual coronary lesions, can be estimated noninvasively from standardly acquired CT data based on computational fluid dynamics. FFR-CT was recently approved for clinical use by the Food and Drug Administration and the European Medicines Agency based on its diagnostic accuracy, he said.
The clinical effectiveness of the strategy was demonstrated in the PLATFORM trial which showed a reduction in the rate of invasive angiography without obstructive coronary artery disease from 73% to 12% with the use of FFR-CT. The current findings further demonstrate that the approach improves quality of life outcomes.
Though limited by the use of a consecutive observational design, as opposed to a randomized trial design, the large effect sizes suggest that findings would be similar in a randomized study, Dr. Hlatky said.
“I don’t think this is by chance. The plausibility of it has been explained,” he said, adding that while most people are happy with a normal CT angiography because of the high sensitivity, estimated FFR using the CT technique can be helpful in the setting of uncertainty.
“If you see something and you’re not sure if it’s significant, and if the estimated FFR from this technique is normal, that’s extremely reassuring that it’s just something you’re seeing but it’s not necessarily obstructing flow,” he said.
He added that “this would be best tested by doing a real, true, randomized study,” but said he considers the findings to be “quite interesting and completely in line with the clinical results.”
The technique is “entering progressively into practice in Europe,” said Dr. de Bruyne, who is a PLATFORM coinvestigator. “It is already used in clinical practice. You get the anatomy and physiology at the same time and same place. It is a really important paradigm change,” he said.
Dr. Hlatky and Dr. de Bruyne reported receiving research grants from HeartFlow, which supported the study.
SAN FRANCISCO – Estimating fractional flow reserve with computed tomography appears to reduce resource use and costs when compared with invasive coronary angiography in stable patients with possible symptoms of coronary disease, according to a substudy of the prospective, multicenter PLATFORM trial.
Fractional flow reserve estimated by CT (FFR-CT) was also associated with greater improvement in quality of life measures during the 90-day study period, when compared with usual noninvasive testing, Dr. Mark A. Hlatky of Stanford (Calif.) University reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
The PLATFORM trial and substudy data are “game changers,” according to the discussant, Dr. Bernard de Bruyne of Cardiovascular Center Aalst, Belgium, who predicted that if the findings are confirmed in other studies, “this kind of approach will probably largely replace the presently available noninvasive approaches and noninvasive stress testing.”
To assess the effect of using FFR-CT rather than usual care on cost and quality of life, patients with stable symptoms, intermediate probability of CAD (the pretest CAD probability was 49%), and no established CAD diagnosis were enrolled into one of two strata based on whether invasive or noninvasive diagnostic testing was planned. Among 193 patients in the planned invasive testing group who underwent FFR-CT, costs were reduced by 32%, compared with 187 patients in the group who received usual care ($7,343 vs. $10,734). The difference was highly statistically significant.
Among 104 patients in the planned noninvasive testing group who underwent FFR-CT, costs did not differ significantly, compared with 100 in that group who received usual care ($2,679 vs. $2,137), Dr. Hlatky reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.
These findings persisted after propensity score matching, he noted.
Furthermore, scores on each of three quality of life measures improved in the overall study population, and scores in the noninvasive stratum improved more with FFR-CT than with usual care. For example, Seattle Angina Questionnaire scores were 19.5 vs. 11.4, EuroQOL scores were 0.08 vs. 0.03, and visual analog scale scores were 4.1 vs. 2.3 in the groups, respectively. The improvements in the invasive cohort were similar with FFR-CT and usual care, Dr. Hlatky noted.
The findings, published simultaneously online (J Am Coll Cardiol. 2015. doi:10.1016/j.jacc.2015.09.051), suggest that the combination of anatomic and functional data provided by an FFR-CT–guided testing strategy may lead to more selective use of invasive procedures than relying solely on the anatomic data provided by invasive coronary angiography, Dr. Hlatky reported.
He explained that FFR, which assesses the functional significance of individual coronary lesions, can be estimated noninvasively from standardly acquired CT data based on computational fluid dynamics. FFR-CT was recently approved for clinical use by the Food and Drug Administration and the European Medicines Agency based on its diagnostic accuracy, he said.
The clinical effectiveness of the strategy was demonstrated in the PLATFORM trial which showed a reduction in the rate of invasive angiography without obstructive coronary artery disease from 73% to 12% with the use of FFR-CT. The current findings further demonstrate that the approach improves quality of life outcomes.
Though limited by the use of a consecutive observational design, as opposed to a randomized trial design, the large effect sizes suggest that findings would be similar in a randomized study, Dr. Hlatky said.
“I don’t think this is by chance. The plausibility of it has been explained,” he said, adding that while most people are happy with a normal CT angiography because of the high sensitivity, estimated FFR using the CT technique can be helpful in the setting of uncertainty.
“If you see something and you’re not sure if it’s significant, and if the estimated FFR from this technique is normal, that’s extremely reassuring that it’s just something you’re seeing but it’s not necessarily obstructing flow,” he said.
He added that “this would be best tested by doing a real, true, randomized study,” but said he considers the findings to be “quite interesting and completely in line with the clinical results.”
The technique is “entering progressively into practice in Europe,” said Dr. de Bruyne, who is a PLATFORM coinvestigator. “It is already used in clinical practice. You get the anatomy and physiology at the same time and same place. It is a really important paradigm change,” he said.
Dr. Hlatky and Dr. de Bruyne reported receiving research grants from HeartFlow, which supported the study.
AT TCT 2015
Key clinical point: Estimating fractional flow reserve with computed tomography appears to reduce resource use and costs when compared with invasive coronary angiography in stable patients with possible symptoms of coronary disease.
Major finding: Costs in patients in the planned invasive testing group who underwent FFR-CT were reduced by 32% compared with those who received usual care ($7,347 vs. $10,734).
Data source: A prospective, multicenter substudy of the PLATFORM trial, involving 584 patients.
Disclosures: Dr. Hlatky reported receiving research grants from HeartFlow, which supported the study.
Hemorrhage control after pelvic fracture: Methods vary widely
LAS VEGAS – Methods for controlling hemorrhage from severe pelvic fractures vary widely across institutions, according to findings from a prospective observational study.
In particular, the findings from the 2-year multicenter study of 1,339 patients show that resuscitative endovascular balloon occlusion of the aorta (REBOA) is rarely used, despite its inclusion in recent management algorithms, Dr. Todd W. Costantini reported at the annual meeting of the American Association for the Surgery of Trauma (AAST).
The most common methods used for hemorrhage control were angioembolization alone and external fixator placement alone, used in 55 (4.1%) and 78 (5.8%) patients, respectively. These methods were also used in 19 (10.7%) and 17 (9.6%) of the 178 patients of the overall study population who presented in shock, said Dr. Costantini of the University of California San Diego Health System.
Other methods included preperitoneal pelvic packing alone in 20 patients overall and 6 patients in shock, embolization plus external fixator in 11 patients overall and 6 patients in shock, embolization and pelvic packing in 6 patients overall and 2 patients in shock, external fixator plus pelvic packing in 6 patients overall and 1 patient in shock, embolization plus external fixator plus pelvic packing in 5 patients overall and 1 patient in shock.
“As most pelvic fracture algorithms suggest the use of preperitoneal packing prior to embolization in patients who present with hemodynamic instability, we were interested to find that only two patients [in shock] were treated with this method,” Dr. Costantini said.
Further, REBOA with or without any other method was used in only five patients overall (0.4%) and five patients in shock (2.8%), and all of these were from only 1 of the 11 participating centers, he noted.
Study subjects were adults with a mean age of 47 years with pelvic fracture from blunt trauma, and 57% were men. The mean Injury Severity Score was high at 19.2 on a scale of 75. Associated injury was common; 32% had an abbreviated injury scale (AIS) score of 3 or higher (out of 6) for chest injury.
The average intensive care unit length of stay was 8.2 days, and the average hospital length of stay was 10.9 days. In-hospital mortality was 9%.
“Pelvic fractures are associated with significant disability, demonstrated by the fact that only 43% of patients were discharged home from the hospital after admission for pelvic fractures. The remainder required ongoing care in either skilled nursing facilities or acute rehab facilities,” he said.
Of the patients who met criteria for shock, the mean age was 44 years, 59% were men, and the mean ISS was 28.2, with nearly half having a chest AIS of 3 or greater, nearly 39% having a head AIS of 3 or greater, and 32% having an abdominal AIS of 3 or greater. The mean ICU stay was 11.6 days, and the mean hospital stay, 19.3 days. In-hospital mortality among those presenting in shock was 32%.
Most patients underwent computed tomography, and arterial blush was noted in 10% of cases. Angiography was used in 148 patients, and half of those were noted to have contrast extravasation.
Therapeutic angioembolization was used in 79 patients (5.9%) overall, and in 60% of those undergoing angiography. The most common indication for angiography was ongoing hemorrhage, hemodynamic instability, and blush on CT scan.
The findings demonstrate significant variability in the approach to hemorrhage control across participating institutions.
“We found that there is currently limited use of REBOA in the treatment of hemorrhage associated with pelvic fracture. However, this may change as management strategies evolve with advances in training and technology,” Dr. Costantini concluded.
As a discussant for Dr. Costantini’s paper, Dr. Walter Biffl of the University of Colorado, Denver, expressed concern regarding the lack of adherence to management algorithms, saying that the data suggest a lack of standardization and orderly application of principles that have been shown to reduce mortality.
“Only 19% had pelvic binding. In our algorithm, 100% get that. And 85% of those in shock had CT scans. In our algorithm that comes after all these other interventions,” he said. “This study clearly opens the door for further research. If we could start with a pelvic binder and hemostatic resuscitation and maybe add REBOA for the severely hypertensive patients, maybe we can begin to determine the goals and efficacy of more interventions,” he said.
Dr. Costantini’s study was supported by the AAST Multi-Institutional Trials Committee. He reported having no disclosures.
LAS VEGAS – Methods for controlling hemorrhage from severe pelvic fractures vary widely across institutions, according to findings from a prospective observational study.
In particular, the findings from the 2-year multicenter study of 1,339 patients show that resuscitative endovascular balloon occlusion of the aorta (REBOA) is rarely used, despite its inclusion in recent management algorithms, Dr. Todd W. Costantini reported at the annual meeting of the American Association for the Surgery of Trauma (AAST).
The most common methods used for hemorrhage control were angioembolization alone and external fixator placement alone, used in 55 (4.1%) and 78 (5.8%) patients, respectively. These methods were also used in 19 (10.7%) and 17 (9.6%) of the 178 patients of the overall study population who presented in shock, said Dr. Costantini of the University of California San Diego Health System.
Other methods included preperitoneal pelvic packing alone in 20 patients overall and 6 patients in shock, embolization plus external fixator in 11 patients overall and 6 patients in shock, embolization and pelvic packing in 6 patients overall and 2 patients in shock, external fixator plus pelvic packing in 6 patients overall and 1 patient in shock, embolization plus external fixator plus pelvic packing in 5 patients overall and 1 patient in shock.
“As most pelvic fracture algorithms suggest the use of preperitoneal packing prior to embolization in patients who present with hemodynamic instability, we were interested to find that only two patients [in shock] were treated with this method,” Dr. Costantini said.
Further, REBOA with or without any other method was used in only five patients overall (0.4%) and five patients in shock (2.8%), and all of these were from only 1 of the 11 participating centers, he noted.
Study subjects were adults with a mean age of 47 years with pelvic fracture from blunt trauma, and 57% were men. The mean Injury Severity Score was high at 19.2 on a scale of 75. Associated injury was common; 32% had an abbreviated injury scale (AIS) score of 3 or higher (out of 6) for chest injury.
The average intensive care unit length of stay was 8.2 days, and the average hospital length of stay was 10.9 days. In-hospital mortality was 9%.
“Pelvic fractures are associated with significant disability, demonstrated by the fact that only 43% of patients were discharged home from the hospital after admission for pelvic fractures. The remainder required ongoing care in either skilled nursing facilities or acute rehab facilities,” he said.
Of the patients who met criteria for shock, the mean age was 44 years, 59% were men, and the mean ISS was 28.2, with nearly half having a chest AIS of 3 or greater, nearly 39% having a head AIS of 3 or greater, and 32% having an abdominal AIS of 3 or greater. The mean ICU stay was 11.6 days, and the mean hospital stay, 19.3 days. In-hospital mortality among those presenting in shock was 32%.
Most patients underwent computed tomography, and arterial blush was noted in 10% of cases. Angiography was used in 148 patients, and half of those were noted to have contrast extravasation.
Therapeutic angioembolization was used in 79 patients (5.9%) overall, and in 60% of those undergoing angiography. The most common indication for angiography was ongoing hemorrhage, hemodynamic instability, and blush on CT scan.
The findings demonstrate significant variability in the approach to hemorrhage control across participating institutions.
“We found that there is currently limited use of REBOA in the treatment of hemorrhage associated with pelvic fracture. However, this may change as management strategies evolve with advances in training and technology,” Dr. Costantini concluded.
As a discussant for Dr. Costantini’s paper, Dr. Walter Biffl of the University of Colorado, Denver, expressed concern regarding the lack of adherence to management algorithms, saying that the data suggest a lack of standardization and orderly application of principles that have been shown to reduce mortality.
“Only 19% had pelvic binding. In our algorithm, 100% get that. And 85% of those in shock had CT scans. In our algorithm that comes after all these other interventions,” he said. “This study clearly opens the door for further research. If we could start with a pelvic binder and hemostatic resuscitation and maybe add REBOA for the severely hypertensive patients, maybe we can begin to determine the goals and efficacy of more interventions,” he said.
Dr. Costantini’s study was supported by the AAST Multi-Institutional Trials Committee. He reported having no disclosures.
LAS VEGAS – Methods for controlling hemorrhage from severe pelvic fractures vary widely across institutions, according to findings from a prospective observational study.
In particular, the findings from the 2-year multicenter study of 1,339 patients show that resuscitative endovascular balloon occlusion of the aorta (REBOA) is rarely used, despite its inclusion in recent management algorithms, Dr. Todd W. Costantini reported at the annual meeting of the American Association for the Surgery of Trauma (AAST).
The most common methods used for hemorrhage control were angioembolization alone and external fixator placement alone, used in 55 (4.1%) and 78 (5.8%) patients, respectively. These methods were also used in 19 (10.7%) and 17 (9.6%) of the 178 patients of the overall study population who presented in shock, said Dr. Costantini of the University of California San Diego Health System.
Other methods included preperitoneal pelvic packing alone in 20 patients overall and 6 patients in shock, embolization plus external fixator in 11 patients overall and 6 patients in shock, embolization and pelvic packing in 6 patients overall and 2 patients in shock, external fixator plus pelvic packing in 6 patients overall and 1 patient in shock, embolization plus external fixator plus pelvic packing in 5 patients overall and 1 patient in shock.
“As most pelvic fracture algorithms suggest the use of preperitoneal packing prior to embolization in patients who present with hemodynamic instability, we were interested to find that only two patients [in shock] were treated with this method,” Dr. Costantini said.
Further, REBOA with or without any other method was used in only five patients overall (0.4%) and five patients in shock (2.8%), and all of these were from only 1 of the 11 participating centers, he noted.
Study subjects were adults with a mean age of 47 years with pelvic fracture from blunt trauma, and 57% were men. The mean Injury Severity Score was high at 19.2 on a scale of 75. Associated injury was common; 32% had an abbreviated injury scale (AIS) score of 3 or higher (out of 6) for chest injury.
The average intensive care unit length of stay was 8.2 days, and the average hospital length of stay was 10.9 days. In-hospital mortality was 9%.
“Pelvic fractures are associated with significant disability, demonstrated by the fact that only 43% of patients were discharged home from the hospital after admission for pelvic fractures. The remainder required ongoing care in either skilled nursing facilities or acute rehab facilities,” he said.
Of the patients who met criteria for shock, the mean age was 44 years, 59% were men, and the mean ISS was 28.2, with nearly half having a chest AIS of 3 or greater, nearly 39% having a head AIS of 3 or greater, and 32% having an abdominal AIS of 3 or greater. The mean ICU stay was 11.6 days, and the mean hospital stay, 19.3 days. In-hospital mortality among those presenting in shock was 32%.
Most patients underwent computed tomography, and arterial blush was noted in 10% of cases. Angiography was used in 148 patients, and half of those were noted to have contrast extravasation.
Therapeutic angioembolization was used in 79 patients (5.9%) overall, and in 60% of those undergoing angiography. The most common indication for angiography was ongoing hemorrhage, hemodynamic instability, and blush on CT scan.
The findings demonstrate significant variability in the approach to hemorrhage control across participating institutions.
“We found that there is currently limited use of REBOA in the treatment of hemorrhage associated with pelvic fracture. However, this may change as management strategies evolve with advances in training and technology,” Dr. Costantini concluded.
As a discussant for Dr. Costantini’s paper, Dr. Walter Biffl of the University of Colorado, Denver, expressed concern regarding the lack of adherence to management algorithms, saying that the data suggest a lack of standardization and orderly application of principles that have been shown to reduce mortality.
“Only 19% had pelvic binding. In our algorithm, 100% get that. And 85% of those in shock had CT scans. In our algorithm that comes after all these other interventions,” he said. “This study clearly opens the door for further research. If we could start with a pelvic binder and hemostatic resuscitation and maybe add REBOA for the severely hypertensive patients, maybe we can begin to determine the goals and efficacy of more interventions,” he said.
Dr. Costantini’s study was supported by the AAST Multi-Institutional Trials Committee. He reported having no disclosures.
AT THE AAST ANNUAL MEETING
Key clinical point: Methods for controlling hemorrhage from severe pelvic fractures vary widely across institutions, according to findings from a prospective observational study.
Major finding: REBOA was used in five patients overall (0.4%) and five patients in shock (2.8%), all from 1 of the 11 participating centers.
Data source: A prospective, multicenter, observational study of 1,339 patients.
Disclosures: Dr. Costantini’s study was supported by the AAST Multi-Institutional Trials Committee. He reported having no disclosures.
TCT: Absorbable metal scaffold performs well in BIOSOLVE II
SAN FRANCISCO – Implantation of the novel DREAMS 2G sirolimus-eluting absorbable metal scaffold in patients with de novo coronary lesions was feasible and had favorable safety and performance outcomes at 6 months in the BIOSOLVE-II trial.
The findings of the prospective, nonrandomized, first-in-human trial suggest that the DREAMS 2G device – made from magnesium alloy with an absorption time of 12 months – could serve as an alternative to absorbable polymeric scaffolds for the treatment of obstructive coronary disease, Dr. Michael Haude of Medical Clinic I, Städtische Kliniken Neuss, Germany, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
In 120 patients with coronary target lesions who completed the trial and follow-up, the mean in-segment late lumen loss at 6 months – the primary endpoint of the study – was 0.27 mm, and in-scaffold late lumen loss was 0.44 mm. Discernable vasomotion was documented in 80% of a subgroup of 25 patients, he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Among patients who underwent additional assessment, intravascular ultrasound showed preservation of the scaffold area (mean of 6.24 mm2 post procedure vs. 6.21 mm2 at 6 months) with a low mean neointimal area (0.08 mm2). No intraluminal mass was detected on optical coherence tomography, he noted.
Four patients (3%) experienced target lesion failure, and one died from cardiac death.
Periprocedural myocardial infarction occurred in one patient, and clinically driven target lesion revascularization was required in two patients (1.7%).
No definite or probable scaffold thrombosis was observed, Dr. Haude said.
Study subjects were enrolled during October 2013–May 2015 at centers in Belgium, Brazil, Denmark, Germany, Singapore, Spain, Switzerland, and the Netherlands. All had stable or unstable angina or documented silent ischemia and no more than two de novo lesions with a reference vessel diameter between 2.2 and 3.7 mm. The results were published online concurrently with Dr. Haude’s presentation (Lancet. 2015 Oct 12. doi:10.1016/S0140-6736[15]00447-X)
The findings demonstrate improved lumen loss with the DREAMS 2G device, compared with precursor devices, he said.
“If we compare this to the data that we have for the previous version, the bare version of the magnesium absorbable scaffold, the in-segment lumen loss was 0.83. That went down by 37% to the version with the paclitaxel elusion at 0.52, and then it decreased again by 48% to 0.27 ... without a single stent thrombosis case,” he said.
Absorbable metal scaffolds offer good radial strength, low acute recoil, and high compliance to the vessel geometry. Also, they can be implanted via a single step inflation, and thus can be implanted in a way similar to that of a permanent metal stent, he noted.
They can also be electropolished, which provides softer, round edges that allow for improved trackability and deliverability, he said, noting that the magnesium alloy stent provides the strength of metal, but also provides a potential long-term benefit with its ability to be absorbed over time.
Though limited by the nonrandomized trial design and lack of direct comparison with other permanent stents or scaffolds, as well as by the inclusion of only patients with straightforward de novo lesions and uncertainty about ideal follow-up time, DREAMS 2G offers a potential alternative to polymeric absorbable scaffolds, which are currently the scaffolds that are commercially available , Dr. Haude said.
BIOSOLVE-II was funded by Biotronik AG. Dr. Haude received study grants and lecture fees from Biotronik, Abbott Vascular, Cardiac dimensions, Medtronic, Volcano, and Lilly, as well as consulting fees/honoraria from Biotronik AG.
SAN FRANCISCO – Implantation of the novel DREAMS 2G sirolimus-eluting absorbable metal scaffold in patients with de novo coronary lesions was feasible and had favorable safety and performance outcomes at 6 months in the BIOSOLVE-II trial.
The findings of the prospective, nonrandomized, first-in-human trial suggest that the DREAMS 2G device – made from magnesium alloy with an absorption time of 12 months – could serve as an alternative to absorbable polymeric scaffolds for the treatment of obstructive coronary disease, Dr. Michael Haude of Medical Clinic I, Städtische Kliniken Neuss, Germany, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
In 120 patients with coronary target lesions who completed the trial and follow-up, the mean in-segment late lumen loss at 6 months – the primary endpoint of the study – was 0.27 mm, and in-scaffold late lumen loss was 0.44 mm. Discernable vasomotion was documented in 80% of a subgroup of 25 patients, he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Among patients who underwent additional assessment, intravascular ultrasound showed preservation of the scaffold area (mean of 6.24 mm2 post procedure vs. 6.21 mm2 at 6 months) with a low mean neointimal area (0.08 mm2). No intraluminal mass was detected on optical coherence tomography, he noted.
Four patients (3%) experienced target lesion failure, and one died from cardiac death.
Periprocedural myocardial infarction occurred in one patient, and clinically driven target lesion revascularization was required in two patients (1.7%).
No definite or probable scaffold thrombosis was observed, Dr. Haude said.
Study subjects were enrolled during October 2013–May 2015 at centers in Belgium, Brazil, Denmark, Germany, Singapore, Spain, Switzerland, and the Netherlands. All had stable or unstable angina or documented silent ischemia and no more than two de novo lesions with a reference vessel diameter between 2.2 and 3.7 mm. The results were published online concurrently with Dr. Haude’s presentation (Lancet. 2015 Oct 12. doi:10.1016/S0140-6736[15]00447-X)
The findings demonstrate improved lumen loss with the DREAMS 2G device, compared with precursor devices, he said.
“If we compare this to the data that we have for the previous version, the bare version of the magnesium absorbable scaffold, the in-segment lumen loss was 0.83. That went down by 37% to the version with the paclitaxel elusion at 0.52, and then it decreased again by 48% to 0.27 ... without a single stent thrombosis case,” he said.
Absorbable metal scaffolds offer good radial strength, low acute recoil, and high compliance to the vessel geometry. Also, they can be implanted via a single step inflation, and thus can be implanted in a way similar to that of a permanent metal stent, he noted.
They can also be electropolished, which provides softer, round edges that allow for improved trackability and deliverability, he said, noting that the magnesium alloy stent provides the strength of metal, but also provides a potential long-term benefit with its ability to be absorbed over time.
Though limited by the nonrandomized trial design and lack of direct comparison with other permanent stents or scaffolds, as well as by the inclusion of only patients with straightforward de novo lesions and uncertainty about ideal follow-up time, DREAMS 2G offers a potential alternative to polymeric absorbable scaffolds, which are currently the scaffolds that are commercially available , Dr. Haude said.
BIOSOLVE-II was funded by Biotronik AG. Dr. Haude received study grants and lecture fees from Biotronik, Abbott Vascular, Cardiac dimensions, Medtronic, Volcano, and Lilly, as well as consulting fees/honoraria from Biotronik AG.
SAN FRANCISCO – Implantation of the novel DREAMS 2G sirolimus-eluting absorbable metal scaffold in patients with de novo coronary lesions was feasible and had favorable safety and performance outcomes at 6 months in the BIOSOLVE-II trial.
The findings of the prospective, nonrandomized, first-in-human trial suggest that the DREAMS 2G device – made from magnesium alloy with an absorption time of 12 months – could serve as an alternative to absorbable polymeric scaffolds for the treatment of obstructive coronary disease, Dr. Michael Haude of Medical Clinic I, Städtische Kliniken Neuss, Germany, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
In 120 patients with coronary target lesions who completed the trial and follow-up, the mean in-segment late lumen loss at 6 months – the primary endpoint of the study – was 0.27 mm, and in-scaffold late lumen loss was 0.44 mm. Discernable vasomotion was documented in 80% of a subgroup of 25 patients, he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Among patients who underwent additional assessment, intravascular ultrasound showed preservation of the scaffold area (mean of 6.24 mm2 post procedure vs. 6.21 mm2 at 6 months) with a low mean neointimal area (0.08 mm2). No intraluminal mass was detected on optical coherence tomography, he noted.
Four patients (3%) experienced target lesion failure, and one died from cardiac death.
Periprocedural myocardial infarction occurred in one patient, and clinically driven target lesion revascularization was required in two patients (1.7%).
No definite or probable scaffold thrombosis was observed, Dr. Haude said.
Study subjects were enrolled during October 2013–May 2015 at centers in Belgium, Brazil, Denmark, Germany, Singapore, Spain, Switzerland, and the Netherlands. All had stable or unstable angina or documented silent ischemia and no more than two de novo lesions with a reference vessel diameter between 2.2 and 3.7 mm. The results were published online concurrently with Dr. Haude’s presentation (Lancet. 2015 Oct 12. doi:10.1016/S0140-6736[15]00447-X)
The findings demonstrate improved lumen loss with the DREAMS 2G device, compared with precursor devices, he said.
“If we compare this to the data that we have for the previous version, the bare version of the magnesium absorbable scaffold, the in-segment lumen loss was 0.83. That went down by 37% to the version with the paclitaxel elusion at 0.52, and then it decreased again by 48% to 0.27 ... without a single stent thrombosis case,” he said.
Absorbable metal scaffolds offer good radial strength, low acute recoil, and high compliance to the vessel geometry. Also, they can be implanted via a single step inflation, and thus can be implanted in a way similar to that of a permanent metal stent, he noted.
They can also be electropolished, which provides softer, round edges that allow for improved trackability and deliverability, he said, noting that the magnesium alloy stent provides the strength of metal, but also provides a potential long-term benefit with its ability to be absorbed over time.
Though limited by the nonrandomized trial design and lack of direct comparison with other permanent stents or scaffolds, as well as by the inclusion of only patients with straightforward de novo lesions and uncertainty about ideal follow-up time, DREAMS 2G offers a potential alternative to polymeric absorbable scaffolds, which are currently the scaffolds that are commercially available , Dr. Haude said.
BIOSOLVE-II was funded by Biotronik AG. Dr. Haude received study grants and lecture fees from Biotronik, Abbott Vascular, Cardiac dimensions, Medtronic, Volcano, and Lilly, as well as consulting fees/honoraria from Biotronik AG.
At TCT 2015
Key clinical point: Implantation of the novel DREAMS 2G sirolimus-eluting absorbable metal scaffold in patients with de novo coronary lesions was feasible and had favorable safety and performance outcomes at 6-months in the BIOSOLVE II trial.
Major finding: The mean in-segment late lumen loss at 6 months – the primary endpoint of the study – was 0.27 mm, compared with 0.83 mm for a bare metal precursor.
Data source: The prospective, nonrandomized, multicenter BIOSOLVE II trial of 120 patients.
Disclosures: BIOSOLVE II was funded by Biotronik AG. Dr. Haude received study grants and lecture fees from Biotronik, Abbott Vascular, Cardiac dimensions, Medtronic, Volcano, and Lilly, as well as consulting fees/honoraria from Biotronik AG.
Baseline factors predict early response to multiple myeloma therapy
CHICAGO – Age and the results of select baseline lab measures reflected early response to initial therapy in a review of 1,304 newly diagnosed patients with symptomatic multiple myeloma.
Characteristics associated with increased odds of achieving very good partial response or better (VGPR+) within four cycles of treatment in the study participants, who were seen between 2001 and 2013, were absolute free light chain difference of more than 175 mg/dL (odds ratio, 2.38), age less than 75 years at diagnosis (OR, 2.18), hemoglobin concentration less than 10/12.5 (OR, 1.68), and IgA vs. IgG serum heavy chain secretion (OR, 1.66), Dr. Moritz Binder of the Mayo Clinic, Rochester, Minn., reported in a poster at the American Society of Hematology Meeting on Hematologic Malignancies.
In patients receiving proteasome inhibitors, better response was associated with creatinine concentrations greater than 1.5 mg/dL (OR, 3.83), calcium concentration less than 9.0 mg/dL (OR, 3.37), and greater absolute free light chain difference greater than 175 mg/dL (OR, 2.50), Dr. Binder noted.
High-risk cytogenetic features, conversely, were not associated with treatment response, he said.
The findings are important because the initial response to therapy in newly diagnosed disease can have an effect on long-term outcomes; achieving at least a VGPR to initial treatment can improve progression-free and overall survival. Further, novel agents and risk-adapted treatment strategies now in use have improved response rates and overall survival, Dr. Binder said, adding that it has been unclear, however, whether baseline laboratory parameters could predict the likelihood of early, deep response to initial therapy.
“The ability to predict the likelihood of response to the current therapies can have implications for the treatment approaches in NDMM,” he wrote.
In this study, 288 patients achieved VGPR+ after 4 months, and those patients had a decreased risk of subsequent mortality (hazard ratio, 0.69). This remained true after adjusting for sex, age, International Staging System stage, bone marrow plasma cell involvement, lactate dehydrogenase concentration, initial treatment regimen group, and hematopoietic stem cell transplantation during the disease course (HR, 0.68), he said.
The three most common regimens with immunomodulators that were used in the cohort were lenalidomide-dexamethasone, thalidomide-dexamethasone, and cyclophosphamide-lenalidomide-dexamethasone, and the three most common regimens with proteasome inhibitors were bortezomib-cyclophosphamide-dexamethasone, bortezomib-lenalidomide-dexamethasone, and bortezomib-dexamethasone.
Dr. Binder reported receiving research funding from ASH. Coauthors reported receiving research funding from Celgene, Janssen, Millennium, and Pfizer, and/or serving in an advisory role for Pfizer.
CHICAGO – Age and the results of select baseline lab measures reflected early response to initial therapy in a review of 1,304 newly diagnosed patients with symptomatic multiple myeloma.
Characteristics associated with increased odds of achieving very good partial response or better (VGPR+) within four cycles of treatment in the study participants, who were seen between 2001 and 2013, were absolute free light chain difference of more than 175 mg/dL (odds ratio, 2.38), age less than 75 years at diagnosis (OR, 2.18), hemoglobin concentration less than 10/12.5 (OR, 1.68), and IgA vs. IgG serum heavy chain secretion (OR, 1.66), Dr. Moritz Binder of the Mayo Clinic, Rochester, Minn., reported in a poster at the American Society of Hematology Meeting on Hematologic Malignancies.
In patients receiving proteasome inhibitors, better response was associated with creatinine concentrations greater than 1.5 mg/dL (OR, 3.83), calcium concentration less than 9.0 mg/dL (OR, 3.37), and greater absolute free light chain difference greater than 175 mg/dL (OR, 2.50), Dr. Binder noted.
High-risk cytogenetic features, conversely, were not associated with treatment response, he said.
The findings are important because the initial response to therapy in newly diagnosed disease can have an effect on long-term outcomes; achieving at least a VGPR to initial treatment can improve progression-free and overall survival. Further, novel agents and risk-adapted treatment strategies now in use have improved response rates and overall survival, Dr. Binder said, adding that it has been unclear, however, whether baseline laboratory parameters could predict the likelihood of early, deep response to initial therapy.
“The ability to predict the likelihood of response to the current therapies can have implications for the treatment approaches in NDMM,” he wrote.
In this study, 288 patients achieved VGPR+ after 4 months, and those patients had a decreased risk of subsequent mortality (hazard ratio, 0.69). This remained true after adjusting for sex, age, International Staging System stage, bone marrow plasma cell involvement, lactate dehydrogenase concentration, initial treatment regimen group, and hematopoietic stem cell transplantation during the disease course (HR, 0.68), he said.
The three most common regimens with immunomodulators that were used in the cohort were lenalidomide-dexamethasone, thalidomide-dexamethasone, and cyclophosphamide-lenalidomide-dexamethasone, and the three most common regimens with proteasome inhibitors were bortezomib-cyclophosphamide-dexamethasone, bortezomib-lenalidomide-dexamethasone, and bortezomib-dexamethasone.
Dr. Binder reported receiving research funding from ASH. Coauthors reported receiving research funding from Celgene, Janssen, Millennium, and Pfizer, and/or serving in an advisory role for Pfizer.
CHICAGO – Age and the results of select baseline lab measures reflected early response to initial therapy in a review of 1,304 newly diagnosed patients with symptomatic multiple myeloma.
Characteristics associated with increased odds of achieving very good partial response or better (VGPR+) within four cycles of treatment in the study participants, who were seen between 2001 and 2013, were absolute free light chain difference of more than 175 mg/dL (odds ratio, 2.38), age less than 75 years at diagnosis (OR, 2.18), hemoglobin concentration less than 10/12.5 (OR, 1.68), and IgA vs. IgG serum heavy chain secretion (OR, 1.66), Dr. Moritz Binder of the Mayo Clinic, Rochester, Minn., reported in a poster at the American Society of Hematology Meeting on Hematologic Malignancies.
In patients receiving proteasome inhibitors, better response was associated with creatinine concentrations greater than 1.5 mg/dL (OR, 3.83), calcium concentration less than 9.0 mg/dL (OR, 3.37), and greater absolute free light chain difference greater than 175 mg/dL (OR, 2.50), Dr. Binder noted.
High-risk cytogenetic features, conversely, were not associated with treatment response, he said.
The findings are important because the initial response to therapy in newly diagnosed disease can have an effect on long-term outcomes; achieving at least a VGPR to initial treatment can improve progression-free and overall survival. Further, novel agents and risk-adapted treatment strategies now in use have improved response rates and overall survival, Dr. Binder said, adding that it has been unclear, however, whether baseline laboratory parameters could predict the likelihood of early, deep response to initial therapy.
“The ability to predict the likelihood of response to the current therapies can have implications for the treatment approaches in NDMM,” he wrote.
In this study, 288 patients achieved VGPR+ after 4 months, and those patients had a decreased risk of subsequent mortality (hazard ratio, 0.69). This remained true after adjusting for sex, age, International Staging System stage, bone marrow plasma cell involvement, lactate dehydrogenase concentration, initial treatment regimen group, and hematopoietic stem cell transplantation during the disease course (HR, 0.68), he said.
The three most common regimens with immunomodulators that were used in the cohort were lenalidomide-dexamethasone, thalidomide-dexamethasone, and cyclophosphamide-lenalidomide-dexamethasone, and the three most common regimens with proteasome inhibitors were bortezomib-cyclophosphamide-dexamethasone, bortezomib-lenalidomide-dexamethasone, and bortezomib-dexamethasone.
Dr. Binder reported receiving research funding from ASH. Coauthors reported receiving research funding from Celgene, Janssen, Millennium, and Pfizer, and/or serving in an advisory role for Pfizer.
AT MHM 2015
Key clinical point: A number of factors predict early response to initial therapy in patients with symptomatic multiple myeloma, according to findings from a review of 1,304 cases.
Major finding: Predictors of early response were greater absolute free light chain difference (OR, 2.38), younger age (OR, 2.18), hemoglobin concentration (OR, 1.68), and IgA vs. IgG heavy chain secretion (OR, 1.66).
Data source: A retrospective cohort study involving 1,304 patients.
Disclosures: Dr. Binder reported receiving research funding from ASH. Coauthors reported receiving research funding from Celgene, Janssen, Millennium, and Pfizer, and/or serving in an advisory role for Pfizer.
Power morcellation risks increase with age
Laparoscopic hysterectomy provides better overall outcomes than either laparoscopic hysterectomy with power morcellation or total abdominal hysterectomy in women with presumed benign gynecologic disease, according to a cohort simulation model.
However, age-related differences in outcomes were apparent in the modeled scenarios, suggesting a need for individualized decision making regarding surgical technique, Dr. Jason D. Wright of Columbia University, New York, and his colleagues reported.
The investigators compared outcomes with the three approaches in a hypothetical cohort of women aged 18-65 years without a preoperative diagnosis of cancer, and found that in women with an underlying malignancy, laparoscopic hysterectomy without power morcellation was the “least costly and most effective modality of hysterectomy” across all scenarios modeled.
When comparing laparoscopic hysterectomy with power morcellation to abdominal hysterectomy, they found that the use of morcellation was associated with 80.83 more intraoperative complications, 199.64 fewer perioperative complications, and 241.80 fewer readmissions per 10,000 women (J Natl Cancer Inst. 2015;109[11]:djv251 doi: 10.1093/jnci/djv251).
Among women younger than age 40 years, laparoscopic hysterectomy with morcellation was associated with 1.57 more cases of disseminated cancer and 0.94 more cancer-associated deaths, but there were 0.97 fewer overall deaths per 10,000 women, compared with abdominal hysterectomy.
The excess cases of disseminated cancer for women who underwent laparoscopy with morcellation increased with age, to 3.75, 12.97, and 47.54 per 10,000 women in those aged 40-49 years, 50-59 years, and 60 years and older, respectively. This translated into excess deaths in all age groups (0.30, 5.07, and 18.14 per 10,000 in those aged 40-49 years, 50-59 years, and 60 years and older, respectively).
Laparoscopic hysterectomy without morcellation was also the least costly approach in all age groups. When compared with abdominal hysterectomy, laparoscopic hysterectomy with morcellation increased life-years among women under age 40 (adding 4.49 years), but decreased life-years in older women (–0.47, –20.64, and –91.19 years per 10,000 women aged 49-50, 50-59, and 60 and older, respectively). But laparoscopic hysterectomy with morcellation became more favorable for those aged 40-49, compared with abdominal hysterectomy, when quality of life was taken into account, with an increase of 11.22 quality-adjusted life-years for that age group.
Although power morcellation, compared with abdominal hysterectomy, was associated with greater quality-adjusted life-years and overall life-years in younger women, the magnitude of benefit was relatively small. And in older women, the risk of electric power morcellation greatly outweighed the benefits, the investigators wrote.
The findings underscore the importance of avoiding unnecessary use of power morcellation, as well as working to detect occult malignancy prior to interventions, they wrote.
The findings are also in accord with a 2014 advisory statement from the Food and Drug Administration warning against the use of electric power morcellators in peri- and postmenopausal women, and demonstrate a need for individualizing surgical technique in all patients and informing patients of the risks of electric power morcellation, the investigators said.
“As women age, the risk of underlying occult malignancy rises, increasing the risks associated with electric power morcellation,” the investigators wrote. “For many women, this risk will outweigh the benefits of minimally invasive surgery, and the procedure should be used with caution.”
The investigators reported having no relevant financial disclosures.
In the wake of reports of dissemination of unrecognized malignancies in patients undergoing laparoscopic hysterectomy with power morcellation of the uterus, the technique has been “virtually discontinued,” despite a lack of analysis of its benefits and potential harms, according to Dr. David G. Mutch.
The work of Wright et al. is a step in the right direction as it begins to assess the real risks of dissemination of malignancy and to determine the benefits and risks to women who might choose to undergo laparoscopy, he wrote in an editorial.
The findings help to more specifically categorize the risk to patients by considering both the risks of dissemination of malignancy and those associated with abdominal hysterectomy.
“More data such as those produced here are needed to better define the real risk so that women give informed consent before undergoing a procedure. Additionally, as other techniques such as morcellation of the uterus in a containment bag become more common, we should obtain data on their safety and efficacy,” he wrote.
Dr. Mutch is with Washington University, St. Louis. He made these remarks in an accompanying editorial (J Natl Cancer Instit. 2005;107[11]:djv283 doi: 10.1093/jnci/djv283).
In the wake of reports of dissemination of unrecognized malignancies in patients undergoing laparoscopic hysterectomy with power morcellation of the uterus, the technique has been “virtually discontinued,” despite a lack of analysis of its benefits and potential harms, according to Dr. David G. Mutch.
The work of Wright et al. is a step in the right direction as it begins to assess the real risks of dissemination of malignancy and to determine the benefits and risks to women who might choose to undergo laparoscopy, he wrote in an editorial.
The findings help to more specifically categorize the risk to patients by considering both the risks of dissemination of malignancy and those associated with abdominal hysterectomy.
“More data such as those produced here are needed to better define the real risk so that women give informed consent before undergoing a procedure. Additionally, as other techniques such as morcellation of the uterus in a containment bag become more common, we should obtain data on their safety and efficacy,” he wrote.
Dr. Mutch is with Washington University, St. Louis. He made these remarks in an accompanying editorial (J Natl Cancer Instit. 2005;107[11]:djv283 doi: 10.1093/jnci/djv283).
In the wake of reports of dissemination of unrecognized malignancies in patients undergoing laparoscopic hysterectomy with power morcellation of the uterus, the technique has been “virtually discontinued,” despite a lack of analysis of its benefits and potential harms, according to Dr. David G. Mutch.
The work of Wright et al. is a step in the right direction as it begins to assess the real risks of dissemination of malignancy and to determine the benefits and risks to women who might choose to undergo laparoscopy, he wrote in an editorial.
The findings help to more specifically categorize the risk to patients by considering both the risks of dissemination of malignancy and those associated with abdominal hysterectomy.
“More data such as those produced here are needed to better define the real risk so that women give informed consent before undergoing a procedure. Additionally, as other techniques such as morcellation of the uterus in a containment bag become more common, we should obtain data on their safety and efficacy,” he wrote.
Dr. Mutch is with Washington University, St. Louis. He made these remarks in an accompanying editorial (J Natl Cancer Instit. 2005;107[11]:djv283 doi: 10.1093/jnci/djv283).
Laparoscopic hysterectomy provides better overall outcomes than either laparoscopic hysterectomy with power morcellation or total abdominal hysterectomy in women with presumed benign gynecologic disease, according to a cohort simulation model.
However, age-related differences in outcomes were apparent in the modeled scenarios, suggesting a need for individualized decision making regarding surgical technique, Dr. Jason D. Wright of Columbia University, New York, and his colleagues reported.
The investigators compared outcomes with the three approaches in a hypothetical cohort of women aged 18-65 years without a preoperative diagnosis of cancer, and found that in women with an underlying malignancy, laparoscopic hysterectomy without power morcellation was the “least costly and most effective modality of hysterectomy” across all scenarios modeled.
When comparing laparoscopic hysterectomy with power morcellation to abdominal hysterectomy, they found that the use of morcellation was associated with 80.83 more intraoperative complications, 199.64 fewer perioperative complications, and 241.80 fewer readmissions per 10,000 women (J Natl Cancer Inst. 2015;109[11]:djv251 doi: 10.1093/jnci/djv251).
Among women younger than age 40 years, laparoscopic hysterectomy with morcellation was associated with 1.57 more cases of disseminated cancer and 0.94 more cancer-associated deaths, but there were 0.97 fewer overall deaths per 10,000 women, compared with abdominal hysterectomy.
The excess cases of disseminated cancer for women who underwent laparoscopy with morcellation increased with age, to 3.75, 12.97, and 47.54 per 10,000 women in those aged 40-49 years, 50-59 years, and 60 years and older, respectively. This translated into excess deaths in all age groups (0.30, 5.07, and 18.14 per 10,000 in those aged 40-49 years, 50-59 years, and 60 years and older, respectively).
Laparoscopic hysterectomy without morcellation was also the least costly approach in all age groups. When compared with abdominal hysterectomy, laparoscopic hysterectomy with morcellation increased life-years among women under age 40 (adding 4.49 years), but decreased life-years in older women (–0.47, –20.64, and –91.19 years per 10,000 women aged 49-50, 50-59, and 60 and older, respectively). But laparoscopic hysterectomy with morcellation became more favorable for those aged 40-49, compared with abdominal hysterectomy, when quality of life was taken into account, with an increase of 11.22 quality-adjusted life-years for that age group.
Although power morcellation, compared with abdominal hysterectomy, was associated with greater quality-adjusted life-years and overall life-years in younger women, the magnitude of benefit was relatively small. And in older women, the risk of electric power morcellation greatly outweighed the benefits, the investigators wrote.
The findings underscore the importance of avoiding unnecessary use of power morcellation, as well as working to detect occult malignancy prior to interventions, they wrote.
The findings are also in accord with a 2014 advisory statement from the Food and Drug Administration warning against the use of electric power morcellators in peri- and postmenopausal women, and demonstrate a need for individualizing surgical technique in all patients and informing patients of the risks of electric power morcellation, the investigators said.
“As women age, the risk of underlying occult malignancy rises, increasing the risks associated with electric power morcellation,” the investigators wrote. “For many women, this risk will outweigh the benefits of minimally invasive surgery, and the procedure should be used with caution.”
The investigators reported having no relevant financial disclosures.
Laparoscopic hysterectomy provides better overall outcomes than either laparoscopic hysterectomy with power morcellation or total abdominal hysterectomy in women with presumed benign gynecologic disease, according to a cohort simulation model.
However, age-related differences in outcomes were apparent in the modeled scenarios, suggesting a need for individualized decision making regarding surgical technique, Dr. Jason D. Wright of Columbia University, New York, and his colleagues reported.
The investigators compared outcomes with the three approaches in a hypothetical cohort of women aged 18-65 years without a preoperative diagnosis of cancer, and found that in women with an underlying malignancy, laparoscopic hysterectomy without power morcellation was the “least costly and most effective modality of hysterectomy” across all scenarios modeled.
When comparing laparoscopic hysterectomy with power morcellation to abdominal hysterectomy, they found that the use of morcellation was associated with 80.83 more intraoperative complications, 199.64 fewer perioperative complications, and 241.80 fewer readmissions per 10,000 women (J Natl Cancer Inst. 2015;109[11]:djv251 doi: 10.1093/jnci/djv251).
Among women younger than age 40 years, laparoscopic hysterectomy with morcellation was associated with 1.57 more cases of disseminated cancer and 0.94 more cancer-associated deaths, but there were 0.97 fewer overall deaths per 10,000 women, compared with abdominal hysterectomy.
The excess cases of disseminated cancer for women who underwent laparoscopy with morcellation increased with age, to 3.75, 12.97, and 47.54 per 10,000 women in those aged 40-49 years, 50-59 years, and 60 years and older, respectively. This translated into excess deaths in all age groups (0.30, 5.07, and 18.14 per 10,000 in those aged 40-49 years, 50-59 years, and 60 years and older, respectively).
Laparoscopic hysterectomy without morcellation was also the least costly approach in all age groups. When compared with abdominal hysterectomy, laparoscopic hysterectomy with morcellation increased life-years among women under age 40 (adding 4.49 years), but decreased life-years in older women (–0.47, –20.64, and –91.19 years per 10,000 women aged 49-50, 50-59, and 60 and older, respectively). But laparoscopic hysterectomy with morcellation became more favorable for those aged 40-49, compared with abdominal hysterectomy, when quality of life was taken into account, with an increase of 11.22 quality-adjusted life-years for that age group.
Although power morcellation, compared with abdominal hysterectomy, was associated with greater quality-adjusted life-years and overall life-years in younger women, the magnitude of benefit was relatively small. And in older women, the risk of electric power morcellation greatly outweighed the benefits, the investigators wrote.
The findings underscore the importance of avoiding unnecessary use of power morcellation, as well as working to detect occult malignancy prior to interventions, they wrote.
The findings are also in accord with a 2014 advisory statement from the Food and Drug Administration warning against the use of electric power morcellators in peri- and postmenopausal women, and demonstrate a need for individualizing surgical technique in all patients and informing patients of the risks of electric power morcellation, the investigators said.
“As women age, the risk of underlying occult malignancy rises, increasing the risks associated with electric power morcellation,” the investigators wrote. “For many women, this risk will outweigh the benefits of minimally invasive surgery, and the procedure should be used with caution.”
The investigators reported having no relevant financial disclosures.
FROM THE JOURNAL OF THE NATIONAL CANCER INSTITUTE
Key clinical point: Laparoscopic hysterectomy without power morcellation was the most effective and least costly method of hysterectomy in women with presumed benign gynecologic disease.
Major finding: The excess deaths associated with laparoscopic hysterectomy with morcellation were 0.30, 5.07, and 18.14 per 10,000 in those aged 40-49 years, 50-59 years, and 60 years and older, respectively, compared with 0.97 fewer deaths in those younger than age 40 years.
Data source: A cohort simulation model involving women aged 18-65 years.
Disclosures: The investigators reported having no relevant financial disclosures.
BCVI: Screen with CT angiography, confirm with DSA
LAS VEGAS – Management of blunt cerebrovascular injuries using 64-channel computed tomographic angiography screening coupled with digital subtraction angiography for a definitive diagnosis is safe and effective for identifying clinically significant injury and for maintaining a low stroke rate, according to a review of 228 cases.
The computed tomographic angiography (CTA) screening was positive in 189 patients (83%), and digital subtraction angiography (DSA) confirmed injury in 104 (55%) of those. The remaining 39 patients were found to have no injury on DSA, Dr. Charles P. Shahan of the University of Tennessee, Memphis reported at the annual meeting of the American Association for the Surgery of Trauma (AAST).
Stroke related to blunt cerebrovascular injury (BCVI) occurred in five patients (4.8%); three of those patients were symptomatic at the time of presentation, and two became symptomatic while on therapy for a known lesion. None of the patients who had a negative screening CTA, including three with injuries missed on CTA, had a stroke, Dr. Shahan said.
The current study follows a prior study reported at the 2013 AAST annual meeting that suggested that 64-channel multidetector CTA could be the primary screening tool for BCVI. The previously used 32-channel multidetector CTA was found to be inadequate, with a sensitivity of only 52%. Sensitivity increased to 68% with the 64-channel CTA, but the positive predictive value remained remarkably low at 36%, he said.
That study led to a change in the screening algorithm, replacing DSA with CTA for screening, and reserving DSA for definitive BCVI diagnosis following a positive CTA or unexplained neurologic findings, he explained, noting that the rationale was that most injuries missed were low-grade injuries less likely to result in further injury, and that with CTA alone, about two-thirds of patients would be treated unnecessarily because of the false-positive rate.
The purpose of the current study was to evaluate outcomes in the wake of the algorithm change and to assess the potential for missed, clinically significant BCVI.
Study subjects were patients who underwent DSA over an 18-month period after implementation of the algorithm change. Most (64%) were men with a mean age of 43 years and a mean injury severity score of 22 out of 75, indicating moderate or severe injury.
The stroke rate was statistically unchanged in the second study, compared with the first. The findings demonstrate the safety and efficacy of the current management algorithm for BCVI, as well as the value of using DSA to identify false-positive CTA findings. In fact, definitive diagnosis by DSA led to avoidance of potentially harmful anticoagulation in 45% of CTA-positive patients, with no increase in the incidence of strokes resulting from injuries missed by CTA, Dr. Shahan said.
“Considering there were 85 false-positive CTAs, and also considering that our average length of heparin time is approximately 7 days prior to reevaluation, we’ve extrapolated this to nearly 600 heparin infusion days that were avoided by confirmatory DSA testing,” he said, concluding that “CTA with 64-channel multidetector technology with experienced radiology staff in a high-volume center can be safe and effective for BCVI screening.”
He added, however, that false-positive rates with CTA continue to necessitate DSA confirmation to avoid overtreatment.
“We feel that CTA screening with DSA confirmation has allowed us to maintain an acceptably low stroke rate and prevented a tremendous amount of unnecessary anticoagulation in these patients,” he said.
Dr. Clay Cothren Burlew, who was an invited discussant for Dr. Shahan’s paper, applauded Dr. Shahan and his colleagues for “continuing to question the validity of CTA as our primary diagnostic modality for BCVI,” and said the findings made her “stop and think, should we all be doing confirmatory angiography? … Are CTAs actually overcalling 45% of the injuries that we identify?”
Dr. Burlew of the University of Colorado, Denver, questioned whether the high rate of false positives is a result of radiologists who “overcall” questionable findings knowing that a confirmatory angiogram will quickly follow.
“I think this evaluation should be a model for others. Each institution should critically review their individual rates and methods of BCVI diagnosis,” she said, adding that “for centers with a marked increase in the identification of BCVI following institution of CTA as their screening tool, consideration of confirmatory angiography is recommended due to the potential false-positive rate of up to 45%.”
However, confirmatory angiography may not be warranted at centers whose screen yields remain the same with no missed injuries, she said.
“All programs should evaluate their injuries, appropriateness of diagnosis, and impact of subsequent treatment. Only then will we have optimal outcomes,” she concluded.
Dr. Shahan and Dr. Burlew reported having no relevant financial disclosures.
LAS VEGAS – Management of blunt cerebrovascular injuries using 64-channel computed tomographic angiography screening coupled with digital subtraction angiography for a definitive diagnosis is safe and effective for identifying clinically significant injury and for maintaining a low stroke rate, according to a review of 228 cases.
The computed tomographic angiography (CTA) screening was positive in 189 patients (83%), and digital subtraction angiography (DSA) confirmed injury in 104 (55%) of those. The remaining 39 patients were found to have no injury on DSA, Dr. Charles P. Shahan of the University of Tennessee, Memphis reported at the annual meeting of the American Association for the Surgery of Trauma (AAST).
Stroke related to blunt cerebrovascular injury (BCVI) occurred in five patients (4.8%); three of those patients were symptomatic at the time of presentation, and two became symptomatic while on therapy for a known lesion. None of the patients who had a negative screening CTA, including three with injuries missed on CTA, had a stroke, Dr. Shahan said.
The current study follows a prior study reported at the 2013 AAST annual meeting that suggested that 64-channel multidetector CTA could be the primary screening tool for BCVI. The previously used 32-channel multidetector CTA was found to be inadequate, with a sensitivity of only 52%. Sensitivity increased to 68% with the 64-channel CTA, but the positive predictive value remained remarkably low at 36%, he said.
That study led to a change in the screening algorithm, replacing DSA with CTA for screening, and reserving DSA for definitive BCVI diagnosis following a positive CTA or unexplained neurologic findings, he explained, noting that the rationale was that most injuries missed were low-grade injuries less likely to result in further injury, and that with CTA alone, about two-thirds of patients would be treated unnecessarily because of the false-positive rate.
The purpose of the current study was to evaluate outcomes in the wake of the algorithm change and to assess the potential for missed, clinically significant BCVI.
Study subjects were patients who underwent DSA over an 18-month period after implementation of the algorithm change. Most (64%) were men with a mean age of 43 years and a mean injury severity score of 22 out of 75, indicating moderate or severe injury.
The stroke rate was statistically unchanged in the second study, compared with the first. The findings demonstrate the safety and efficacy of the current management algorithm for BCVI, as well as the value of using DSA to identify false-positive CTA findings. In fact, definitive diagnosis by DSA led to avoidance of potentially harmful anticoagulation in 45% of CTA-positive patients, with no increase in the incidence of strokes resulting from injuries missed by CTA, Dr. Shahan said.
“Considering there were 85 false-positive CTAs, and also considering that our average length of heparin time is approximately 7 days prior to reevaluation, we’ve extrapolated this to nearly 600 heparin infusion days that were avoided by confirmatory DSA testing,” he said, concluding that “CTA with 64-channel multidetector technology with experienced radiology staff in a high-volume center can be safe and effective for BCVI screening.”
He added, however, that false-positive rates with CTA continue to necessitate DSA confirmation to avoid overtreatment.
“We feel that CTA screening with DSA confirmation has allowed us to maintain an acceptably low stroke rate and prevented a tremendous amount of unnecessary anticoagulation in these patients,” he said.
Dr. Clay Cothren Burlew, who was an invited discussant for Dr. Shahan’s paper, applauded Dr. Shahan and his colleagues for “continuing to question the validity of CTA as our primary diagnostic modality for BCVI,” and said the findings made her “stop and think, should we all be doing confirmatory angiography? … Are CTAs actually overcalling 45% of the injuries that we identify?”
Dr. Burlew of the University of Colorado, Denver, questioned whether the high rate of false positives is a result of radiologists who “overcall” questionable findings knowing that a confirmatory angiogram will quickly follow.
“I think this evaluation should be a model for others. Each institution should critically review their individual rates and methods of BCVI diagnosis,” she said, adding that “for centers with a marked increase in the identification of BCVI following institution of CTA as their screening tool, consideration of confirmatory angiography is recommended due to the potential false-positive rate of up to 45%.”
However, confirmatory angiography may not be warranted at centers whose screen yields remain the same with no missed injuries, she said.
“All programs should evaluate their injuries, appropriateness of diagnosis, and impact of subsequent treatment. Only then will we have optimal outcomes,” she concluded.
Dr. Shahan and Dr. Burlew reported having no relevant financial disclosures.
LAS VEGAS – Management of blunt cerebrovascular injuries using 64-channel computed tomographic angiography screening coupled with digital subtraction angiography for a definitive diagnosis is safe and effective for identifying clinically significant injury and for maintaining a low stroke rate, according to a review of 228 cases.
The computed tomographic angiography (CTA) screening was positive in 189 patients (83%), and digital subtraction angiography (DSA) confirmed injury in 104 (55%) of those. The remaining 39 patients were found to have no injury on DSA, Dr. Charles P. Shahan of the University of Tennessee, Memphis reported at the annual meeting of the American Association for the Surgery of Trauma (AAST).
Stroke related to blunt cerebrovascular injury (BCVI) occurred in five patients (4.8%); three of those patients were symptomatic at the time of presentation, and two became symptomatic while on therapy for a known lesion. None of the patients who had a negative screening CTA, including three with injuries missed on CTA, had a stroke, Dr. Shahan said.
The current study follows a prior study reported at the 2013 AAST annual meeting that suggested that 64-channel multidetector CTA could be the primary screening tool for BCVI. The previously used 32-channel multidetector CTA was found to be inadequate, with a sensitivity of only 52%. Sensitivity increased to 68% with the 64-channel CTA, but the positive predictive value remained remarkably low at 36%, he said.
That study led to a change in the screening algorithm, replacing DSA with CTA for screening, and reserving DSA for definitive BCVI diagnosis following a positive CTA or unexplained neurologic findings, he explained, noting that the rationale was that most injuries missed were low-grade injuries less likely to result in further injury, and that with CTA alone, about two-thirds of patients would be treated unnecessarily because of the false-positive rate.
The purpose of the current study was to evaluate outcomes in the wake of the algorithm change and to assess the potential for missed, clinically significant BCVI.
Study subjects were patients who underwent DSA over an 18-month period after implementation of the algorithm change. Most (64%) were men with a mean age of 43 years and a mean injury severity score of 22 out of 75, indicating moderate or severe injury.
The stroke rate was statistically unchanged in the second study, compared with the first. The findings demonstrate the safety and efficacy of the current management algorithm for BCVI, as well as the value of using DSA to identify false-positive CTA findings. In fact, definitive diagnosis by DSA led to avoidance of potentially harmful anticoagulation in 45% of CTA-positive patients, with no increase in the incidence of strokes resulting from injuries missed by CTA, Dr. Shahan said.
“Considering there were 85 false-positive CTAs, and also considering that our average length of heparin time is approximately 7 days prior to reevaluation, we’ve extrapolated this to nearly 600 heparin infusion days that were avoided by confirmatory DSA testing,” he said, concluding that “CTA with 64-channel multidetector technology with experienced radiology staff in a high-volume center can be safe and effective for BCVI screening.”
He added, however, that false-positive rates with CTA continue to necessitate DSA confirmation to avoid overtreatment.
“We feel that CTA screening with DSA confirmation has allowed us to maintain an acceptably low stroke rate and prevented a tremendous amount of unnecessary anticoagulation in these patients,” he said.
Dr. Clay Cothren Burlew, who was an invited discussant for Dr. Shahan’s paper, applauded Dr. Shahan and his colleagues for “continuing to question the validity of CTA as our primary diagnostic modality for BCVI,” and said the findings made her “stop and think, should we all be doing confirmatory angiography? … Are CTAs actually overcalling 45% of the injuries that we identify?”
Dr. Burlew of the University of Colorado, Denver, questioned whether the high rate of false positives is a result of radiologists who “overcall” questionable findings knowing that a confirmatory angiogram will quickly follow.
“I think this evaluation should be a model for others. Each institution should critically review their individual rates and methods of BCVI diagnosis,” she said, adding that “for centers with a marked increase in the identification of BCVI following institution of CTA as their screening tool, consideration of confirmatory angiography is recommended due to the potential false-positive rate of up to 45%.”
However, confirmatory angiography may not be warranted at centers whose screen yields remain the same with no missed injuries, she said.
“All programs should evaluate their injuries, appropriateness of diagnosis, and impact of subsequent treatment. Only then will we have optimal outcomes,” she concluded.
Dr. Shahan and Dr. Burlew reported having no relevant financial disclosures.
AT THE AAST ANNUAL MEETING
Key clinical point: Use of 64-channel CT angiography screening coupled with digital subtraction angiography for a definitive diagnosis of blunt cerebrovascular injury is safe and effective for identifying clinically significant injury and for maintaining a low stroke rate.
Major finding: None of the patients who had a negative screening CTA, including three with injuries missed on CTA, had a stroke.
Data source: A review of 228 patients with possible BCVI.
Disclosures: Dr. Shahan and Dr. Burlew reported having no relevant financial disclosures.
MHM: Novel agents, combos show promise for relapsed/refractory CLL
CHICAGO – Consider using novel agents in chronic lymphocytic leukemia (CLL) patients who are refractory to treatment or who relapse within 2 years of first-line therapy, Dr. John G. Gribben said.
Ibrutinib or idelalisib/rituximab, or other novel agent combinations within clinical trials are his choice in these patients, thus fitness for therapy becomes irrelevant, he said at the American Society of Hematology Meeting on Hematologic Malignancies.
“Of course, I’m particularly excited by the results in CLL of ABT-199. We saw at [the International Workshop on CLL] last week that there are increasing numbers of patients who are on this therapy in combination with anti-CD20 monoclonal antibodies who are achieving minimal residual disease (MRD) eradication and are able to stop that therapy, unlike what we’ve been seeing,” he said. “I have a patient at my own center now who was treated with ABT-199 plus obinutuzumab within a clinical trial – a 17p deletion patient refractory to seven previous lines of therapy. Had a donor, I was trying to get him to transplant, and now he’s MRD-negative and off therapy, having had 6 months of therapy with ABT-199 and obinutuzumab. [This is] a very exciting combination.”
Other novel-novel agent combinations are also being looked at, he noted.
In CLL patients without 17p deletions who progress later than 2 years after initial chemotherapy, novel agents can be considered, as could alternative approaches with chemotherapy.
“But of course, in the setting of p53 deletions or mutations, then ibrutinib or idelalisib/rituximab, or novel agents like ABT-199 within clinical trials become the treatment approach to be thinking about,” he said.
CHICAGO – Consider using novel agents in chronic lymphocytic leukemia (CLL) patients who are refractory to treatment or who relapse within 2 years of first-line therapy, Dr. John G. Gribben said.
Ibrutinib or idelalisib/rituximab, or other novel agent combinations within clinical trials are his choice in these patients, thus fitness for therapy becomes irrelevant, he said at the American Society of Hematology Meeting on Hematologic Malignancies.
“Of course, I’m particularly excited by the results in CLL of ABT-199. We saw at [the International Workshop on CLL] last week that there are increasing numbers of patients who are on this therapy in combination with anti-CD20 monoclonal antibodies who are achieving minimal residual disease (MRD) eradication and are able to stop that therapy, unlike what we’ve been seeing,” he said. “I have a patient at my own center now who was treated with ABT-199 plus obinutuzumab within a clinical trial – a 17p deletion patient refractory to seven previous lines of therapy. Had a donor, I was trying to get him to transplant, and now he’s MRD-negative and off therapy, having had 6 months of therapy with ABT-199 and obinutuzumab. [This is] a very exciting combination.”
Other novel-novel agent combinations are also being looked at, he noted.
In CLL patients without 17p deletions who progress later than 2 years after initial chemotherapy, novel agents can be considered, as could alternative approaches with chemotherapy.
“But of course, in the setting of p53 deletions or mutations, then ibrutinib or idelalisib/rituximab, or novel agents like ABT-199 within clinical trials become the treatment approach to be thinking about,” he said.
CHICAGO – Consider using novel agents in chronic lymphocytic leukemia (CLL) patients who are refractory to treatment or who relapse within 2 years of first-line therapy, Dr. John G. Gribben said.
Ibrutinib or idelalisib/rituximab, or other novel agent combinations within clinical trials are his choice in these patients, thus fitness for therapy becomes irrelevant, he said at the American Society of Hematology Meeting on Hematologic Malignancies.
“Of course, I’m particularly excited by the results in CLL of ABT-199. We saw at [the International Workshop on CLL] last week that there are increasing numbers of patients who are on this therapy in combination with anti-CD20 monoclonal antibodies who are achieving minimal residual disease (MRD) eradication and are able to stop that therapy, unlike what we’ve been seeing,” he said. “I have a patient at my own center now who was treated with ABT-199 plus obinutuzumab within a clinical trial – a 17p deletion patient refractory to seven previous lines of therapy. Had a donor, I was trying to get him to transplant, and now he’s MRD-negative and off therapy, having had 6 months of therapy with ABT-199 and obinutuzumab. [This is] a very exciting combination.”
Other novel-novel agent combinations are also being looked at, he noted.
In CLL patients without 17p deletions who progress later than 2 years after initial chemotherapy, novel agents can be considered, as could alternative approaches with chemotherapy.
“But of course, in the setting of p53 deletions or mutations, then ibrutinib or idelalisib/rituximab, or novel agents like ABT-199 within clinical trials become the treatment approach to be thinking about,” he said.
EXPERT ANALYSIS FROM MHM 2015
MHM: Novel agents, combos show promise for relapsed/refractory CLL
CHICAGO – Consider using novel agents in chronic lymphocytic leukemia (CLL) patients who are refractory to treatment or who relapse within 2 years of first-line therapy, Dr. John G. Gribben said.
Ibrutinib or idelalisib/rituximab, or other novel agent combinations within clinical trials are his choice in these patients, thus fitness for therapy becomes irrelevant, he said at the American Society of Hematology Meeting on Hematologic Malignancies.
“Of course, I’m particularly excited by the results in CLL of ABT-199. We saw at [the International Workshop on CLL] last week that there are increasing numbers of patients who are on this therapy in combination with anti-CD20 monoclonal antibodies who are achieving minimal residual disease (MRD) eradication and are able to stop that therapy, unlike what we’ve been seeing,” he said. “I have a patient at my own center now who was treated with ABT-199 plus obinutuzumab within a clinical trial – a 17p deletion patient refractory to seven previous lines of therapy. Had a donor, I was trying to get him to transplant, and now he’s MRD-negative and off therapy, having had 6 months of therapy with ABT-199 and obinutuzumab. [This is] a very exciting combination.”
Other novel-novel agent combinations are also being looked at, he noted.
In CLL patients without 17p deletions who progress later than 2 years after initial chemotherapy, novel agents can be considered, as could alternative approaches with chemotherapy.
“But of course, in the setting of p53 deletions or mutations, then ibrutinib or idelalisib/rituximab, or novel agents like ABT-199 within clinical trials become the treatment approach to be thinking about,” he said.
CHICAGO – Consider using novel agents in chronic lymphocytic leukemia (CLL) patients who are refractory to treatment or who relapse within 2 years of first-line therapy, Dr. John G. Gribben said.
Ibrutinib or idelalisib/rituximab, or other novel agent combinations within clinical trials are his choice in these patients, thus fitness for therapy becomes irrelevant, he said at the American Society of Hematology Meeting on Hematologic Malignancies.
“Of course, I’m particularly excited by the results in CLL of ABT-199. We saw at [the International Workshop on CLL] last week that there are increasing numbers of patients who are on this therapy in combination with anti-CD20 monoclonal antibodies who are achieving minimal residual disease (MRD) eradication and are able to stop that therapy, unlike what we’ve been seeing,” he said. “I have a patient at my own center now who was treated with ABT-199 plus obinutuzumab within a clinical trial – a 17p deletion patient refractory to seven previous lines of therapy. Had a donor, I was trying to get him to transplant, and now he’s MRD-negative and off therapy, having had 6 months of therapy with ABT-199 and obinutuzumab. [This is] a very exciting combination.”
Other novel-novel agent combinations are also being looked at, he noted.
In CLL patients without 17p deletions who progress later than 2 years after initial chemotherapy, novel agents can be considered, as could alternative approaches with chemotherapy.
“But of course, in the setting of p53 deletions or mutations, then ibrutinib or idelalisib/rituximab, or novel agents like ABT-199 within clinical trials become the treatment approach to be thinking about,” he said.
CHICAGO – Consider using novel agents in chronic lymphocytic leukemia (CLL) patients who are refractory to treatment or who relapse within 2 years of first-line therapy, Dr. John G. Gribben said.
Ibrutinib or idelalisib/rituximab, or other novel agent combinations within clinical trials are his choice in these patients, thus fitness for therapy becomes irrelevant, he said at the American Society of Hematology Meeting on Hematologic Malignancies.
“Of course, I’m particularly excited by the results in CLL of ABT-199. We saw at [the International Workshop on CLL] last week that there are increasing numbers of patients who are on this therapy in combination with anti-CD20 monoclonal antibodies who are achieving minimal residual disease (MRD) eradication and are able to stop that therapy, unlike what we’ve been seeing,” he said. “I have a patient at my own center now who was treated with ABT-199 plus obinutuzumab within a clinical trial – a 17p deletion patient refractory to seven previous lines of therapy. Had a donor, I was trying to get him to transplant, and now he’s MRD-negative and off therapy, having had 6 months of therapy with ABT-199 and obinutuzumab. [This is] a very exciting combination.”
Other novel-novel agent combinations are also being looked at, he noted.
In CLL patients without 17p deletions who progress later than 2 years after initial chemotherapy, novel agents can be considered, as could alternative approaches with chemotherapy.
“But of course, in the setting of p53 deletions or mutations, then ibrutinib or idelalisib/rituximab, or novel agents like ABT-199 within clinical trials become the treatment approach to be thinking about,” he said.
EXPERT ANALYSIS FROM MHM 2015
CLL Therapy: Focus on comorbidities, not age
CHICAGO – The majority of patients with chronic lymphocytic leukemia (CLL) are elderly patients over age 65 years, which underscores the need for a careful assessment of fitness for therapy – not necessarily because of age, but because of comorbidity burden, according to Dr. John G. Gribben.
In fact, 68% of CLL patients are over age 65 years (median, 71 years), and 41% are over age 75 years. Perhaps more importantly, 89% of elderly CLL patients have one or more comorbidities, and 46% have at least one major comorbidity, said Dr. Gribben of Barts Cancer Institute, Queen Mary University of London.
Conventional wisdom has long suggested that CLL shortens the life span only in younger patients; older patients were thought to be more likely “to die with CLL rather than of CLL,” he said at the American Society of Hematology Meeting on Hematologic Malignancies.
However, recent findings suggest that CLL shortens the life span of elderly patients as well, he noted.
“I think we probably have been undertreating and underthinking about the impact that CLL can have on these more elderly patients, and I think it does represent an area of unmet need,” he said.
Treatment options in the elderly include FCR (fludarabine, cyclophosphamide, rituximab) in those deemed fit enough to tolerate the regimen, he said, adding, “if you are concerned about neutropenia associated with FCR, there are those who use rituximab-fludarabine [RF], and that’s certainly a good option.”
However, in those with an 11q abnormality, good data show that the addition of the alkylator does add benefit. “I do think that FCR is worthwhile pushing [in those cases],” he said.
Bendamustine-rituximab is also an attractive option, as demonstrated in the CLL10 trial, but it is important to remember that patients in that trial were “fit, healthy patients” based on Clinical Illness Rating Scale (CIRS) scores of less than 6; they were patients who were deemed fit to be randomized to receive FCR.
Chlorambucil-based therapies administered with anti-CD20 monoclonal antibodies are also an option, as are novel agents in those with 17p deletions or a P53 mutation, he said.
When it comes to assessing elderly patients’ fitness for therapy, comorbidities play a more important role than age, he said, explaining that many patients over age 65 are very fit and would do well with therapies such as FCR.
For this reason, comorbidities should be the determining factor in treatment selection, he said.
No standard criteria for assessing fitness exist, but there are a few tools that can help.
Eastern Cooperative Oncology Group performance status and organ function (for example, creatinine clearance) can be helpful and often are used in trial settings, as are criteria for excluding patients from participation, but CIRS, used by the German CLL study group, is a more formal tool for assessing comorbidity.
The German group is not the first to use the tool – CIRS is a widely validated test that provides an objective measurement of fitness for more aggressive chemotherapy regimens – but the group did demonstrate in CLL11 that it could be used to enroll more elderly patients with comorbidities into clinical trials, Dr. Gribben said.
A CIRS score of 6 or lower indicates fitness, whereas increasing scores indicate an increasing lack of fitness, he explained, noting that “like every scoring system there are some issues … somebody could easily have a score higher than 6 with comorbidities that really don’t impact on chemotherapy tolerability.
“But in general terms, this is a good way to be making these sorts of assessments,” he said.
Dr. Gribben has received research funding from the National Institutes of Health, Cancer Research UK, MRC, and Wellcome Trust. He has received honoraria from Roche/Genentech, Celgene, Janssen, Pharmacyclics, Gilead, Mundipharma, Infinity, TG Therapeutics, and Ascerta, and he has a patent or receives royalties from Celgene. He also has been the principal investigator on a clinical trial for Roche, Takeda, Pharmacyclics, Gilead, and Infinity.
CHICAGO – The majority of patients with chronic lymphocytic leukemia (CLL) are elderly patients over age 65 years, which underscores the need for a careful assessment of fitness for therapy – not necessarily because of age, but because of comorbidity burden, according to Dr. John G. Gribben.
In fact, 68% of CLL patients are over age 65 years (median, 71 years), and 41% are over age 75 years. Perhaps more importantly, 89% of elderly CLL patients have one or more comorbidities, and 46% have at least one major comorbidity, said Dr. Gribben of Barts Cancer Institute, Queen Mary University of London.
Conventional wisdom has long suggested that CLL shortens the life span only in younger patients; older patients were thought to be more likely “to die with CLL rather than of CLL,” he said at the American Society of Hematology Meeting on Hematologic Malignancies.
However, recent findings suggest that CLL shortens the life span of elderly patients as well, he noted.
“I think we probably have been undertreating and underthinking about the impact that CLL can have on these more elderly patients, and I think it does represent an area of unmet need,” he said.
Treatment options in the elderly include FCR (fludarabine, cyclophosphamide, rituximab) in those deemed fit enough to tolerate the regimen, he said, adding, “if you are concerned about neutropenia associated with FCR, there are those who use rituximab-fludarabine [RF], and that’s certainly a good option.”
However, in those with an 11q abnormality, good data show that the addition of the alkylator does add benefit. “I do think that FCR is worthwhile pushing [in those cases],” he said.
Bendamustine-rituximab is also an attractive option, as demonstrated in the CLL10 trial, but it is important to remember that patients in that trial were “fit, healthy patients” based on Clinical Illness Rating Scale (CIRS) scores of less than 6; they were patients who were deemed fit to be randomized to receive FCR.
Chlorambucil-based therapies administered with anti-CD20 monoclonal antibodies are also an option, as are novel agents in those with 17p deletions or a P53 mutation, he said.
When it comes to assessing elderly patients’ fitness for therapy, comorbidities play a more important role than age, he said, explaining that many patients over age 65 are very fit and would do well with therapies such as FCR.
For this reason, comorbidities should be the determining factor in treatment selection, he said.
No standard criteria for assessing fitness exist, but there are a few tools that can help.
Eastern Cooperative Oncology Group performance status and organ function (for example, creatinine clearance) can be helpful and often are used in trial settings, as are criteria for excluding patients from participation, but CIRS, used by the German CLL study group, is a more formal tool for assessing comorbidity.
The German group is not the first to use the tool – CIRS is a widely validated test that provides an objective measurement of fitness for more aggressive chemotherapy regimens – but the group did demonstrate in CLL11 that it could be used to enroll more elderly patients with comorbidities into clinical trials, Dr. Gribben said.
A CIRS score of 6 or lower indicates fitness, whereas increasing scores indicate an increasing lack of fitness, he explained, noting that “like every scoring system there are some issues … somebody could easily have a score higher than 6 with comorbidities that really don’t impact on chemotherapy tolerability.
“But in general terms, this is a good way to be making these sorts of assessments,” he said.
Dr. Gribben has received research funding from the National Institutes of Health, Cancer Research UK, MRC, and Wellcome Trust. He has received honoraria from Roche/Genentech, Celgene, Janssen, Pharmacyclics, Gilead, Mundipharma, Infinity, TG Therapeutics, and Ascerta, and he has a patent or receives royalties from Celgene. He also has been the principal investigator on a clinical trial for Roche, Takeda, Pharmacyclics, Gilead, and Infinity.
CHICAGO – The majority of patients with chronic lymphocytic leukemia (CLL) are elderly patients over age 65 years, which underscores the need for a careful assessment of fitness for therapy – not necessarily because of age, but because of comorbidity burden, according to Dr. John G. Gribben.
In fact, 68% of CLL patients are over age 65 years (median, 71 years), and 41% are over age 75 years. Perhaps more importantly, 89% of elderly CLL patients have one or more comorbidities, and 46% have at least one major comorbidity, said Dr. Gribben of Barts Cancer Institute, Queen Mary University of London.
Conventional wisdom has long suggested that CLL shortens the life span only in younger patients; older patients were thought to be more likely “to die with CLL rather than of CLL,” he said at the American Society of Hematology Meeting on Hematologic Malignancies.
However, recent findings suggest that CLL shortens the life span of elderly patients as well, he noted.
“I think we probably have been undertreating and underthinking about the impact that CLL can have on these more elderly patients, and I think it does represent an area of unmet need,” he said.
Treatment options in the elderly include FCR (fludarabine, cyclophosphamide, rituximab) in those deemed fit enough to tolerate the regimen, he said, adding, “if you are concerned about neutropenia associated with FCR, there are those who use rituximab-fludarabine [RF], and that’s certainly a good option.”
However, in those with an 11q abnormality, good data show that the addition of the alkylator does add benefit. “I do think that FCR is worthwhile pushing [in those cases],” he said.
Bendamustine-rituximab is also an attractive option, as demonstrated in the CLL10 trial, but it is important to remember that patients in that trial were “fit, healthy patients” based on Clinical Illness Rating Scale (CIRS) scores of less than 6; they were patients who were deemed fit to be randomized to receive FCR.
Chlorambucil-based therapies administered with anti-CD20 monoclonal antibodies are also an option, as are novel agents in those with 17p deletions or a P53 mutation, he said.
When it comes to assessing elderly patients’ fitness for therapy, comorbidities play a more important role than age, he said, explaining that many patients over age 65 are very fit and would do well with therapies such as FCR.
For this reason, comorbidities should be the determining factor in treatment selection, he said.
No standard criteria for assessing fitness exist, but there are a few tools that can help.
Eastern Cooperative Oncology Group performance status and organ function (for example, creatinine clearance) can be helpful and often are used in trial settings, as are criteria for excluding patients from participation, but CIRS, used by the German CLL study group, is a more formal tool for assessing comorbidity.
The German group is not the first to use the tool – CIRS is a widely validated test that provides an objective measurement of fitness for more aggressive chemotherapy regimens – but the group did demonstrate in CLL11 that it could be used to enroll more elderly patients with comorbidities into clinical trials, Dr. Gribben said.
A CIRS score of 6 or lower indicates fitness, whereas increasing scores indicate an increasing lack of fitness, he explained, noting that “like every scoring system there are some issues … somebody could easily have a score higher than 6 with comorbidities that really don’t impact on chemotherapy tolerability.
“But in general terms, this is a good way to be making these sorts of assessments,” he said.
Dr. Gribben has received research funding from the National Institutes of Health, Cancer Research UK, MRC, and Wellcome Trust. He has received honoraria from Roche/Genentech, Celgene, Janssen, Pharmacyclics, Gilead, Mundipharma, Infinity, TG Therapeutics, and Ascerta, and he has a patent or receives royalties from Celgene. He also has been the principal investigator on a clinical trial for Roche, Takeda, Pharmacyclics, Gilead, and Infinity.
AT MHM 2015
