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Prescribers mostly ignore clopidogrel pharmacogenomic profiling
ANAHEIM, CALIF. – The boxed warning recommending pharmacogenomic testing of patients receiving clopidogrel to identify reduced metabolizers seems to be playing to a largely deaf audience.
Even when handed information on whether each clopidogrel-treated patient was a poor metabolizer of the drug, treating physicians usually did not switch them to a different antiplatelet drug, ticagrelor, that would be fully effective despite the patient’s reduced-metabolizer status. And clinicians who started patients on ticagrelor did not usually switch those with a good clopidogrel-metabolizing profile to the safer drug, clopidogrel, after learning that clopidogrel would be fully effective.
“Routine reporting of pharmacogenomics test results for acute coronary syndrome patients treated with P2Y12-inhibitor therapy had an uncertain yield and little impact on P2Y12-inhibitor switching,” E. Magnus Ohman, MBBS, said at the American Heart Association scientific sessions.
The study’s design gave each participating clinician free rein on whether to prescribe clopidogrel or ticagrelor (Brilinta) initially, and switching between the drugs was possible at any time after the initial prescription. At the trial’s start, 1,704 patients (56%) were on ticagrelor and 1,333 (44%) were on clopidogrel.
Pharmacogenomic testing showed that 34% of all patients were ultrametabolizers and 38% were extensive metabolizers. Patients in either of these categories metabolize enough clopidogrel into the active form to get full benefit from the drug and derive no additional efficacy benefit from switching to another P2Y12 inhibitor, such as ticagrelor or prasugrel (Effient) – drugs unaffected by metabolizer status. Testing also identified 25% of patients as intermediate metabolizers, who carry one loss-of-function allele for the CYP2C19 gene, and 3% were reduced metabolizers, who are homozygous for loss-of-function alleles. Standard practice is not to treat intermediate or reduced metabolizers with clopidogrel because they would not get an adequate antiplatelet effect; instead, these patients are usually treated with ticagrelor or with prasugrel when it’s an option.
After receiving the results regarding the clopidogrel-metabolizing status for each patient, attending physicians switched the drugs prescribed for only 7% of all patients: 9% of patients initially on ticagrelor and 4% of those initially on clopidogrel, reported Dr. Ohman, professor of medicine at Duke University in Durham, N.C. In addition, Dr. Ohman and his associates asked each participating physician who made a switch about his or her reasons for doing so. Of the patients who switched from clopidogrel to ticagrelor, only 23 were switched because of their pharmacogenomic results; this represents fewer than half of those who switched and only 2% of all patients who took clopidogrel. Only one patient changed from ticagrelor to clopidogrel based on pharmacogenomic results, representing 0.06% of all patients on ticagrelor.
“We believed the findings do not support the utility of mandatory testing in this context, as most did not act on the information,” Dr. Ohman said.
A major reason for the inertia, Dr. Gurbel suggested, may be the absence of any compelling data proving whether there’s any effect on clinical outcomes for switching reduced metabolizers off of clopidogrel or switching good metabolizers onto it.
“We have no large-scale, prospective data supporting pharmacogenomic-based personalization” of clopidogrel treatment leading to improved outcomes, but “we need to get over that,” he said. “It’s a challenge to get funding for this.” But “the answer is not to give ticagrelor or prasugrel to everyone because then the bleeding rate is too high.”
The findings Dr. Ohman reported came from the Study to Compare the Safety of Rivaroxaban Versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Participants With Acute Coronary Syndrome (GEMINI-ACS-1), which had the primary goal of comparing the safety in acute coronary syndrome patients of a reduced dosage of rivaroxaban plus either clopidogrel or ticagrelor with the safety of aspirin plus one of these P2Y12 inhibitors. The primary endpoint was the rate of clinically significant bleeding events during a year of treatment. The study ran at 371 centers in 21 countries and showed similar bleeding rates in both treatment arms (Lancet. 2017 May 6; 389[10081]:1799-808).
The analysis also showed that patients identified as reduced metabolizers were fivefold more likely to be switched than patients identified as ultra metabolizers, and intermediate metabolizes had a 50% higher switching rate than ultra metabolizers. The rates of both ischemic and major bleeding outcomes were roughly similar across the spectrum of metabolizers, but Dr. Ohman cautioned that the trial was not designed to assess this. Dr. Gurbel urged the investigators to report on outcomes analyzed not just by metabolizer status but also by the treatment they received.
The boxed warning that clopidogrel received in 2010 regarding poor metabolizers led to “regulatory guidance” during design of the GEMINI-ACS-1 trial requiring routine pharmacogenomic testing for clopidogrel-metabolizing status, Dr. Ohman explained.
The trial was funded by Janssen and Bayer, the two companies that jointly market rivaroxaban (Xarelto). Dr. Ohman has been a consultant to Bayer and several other companies including AstraZeneca, the company that markets ticagrelor (Brilinta). He has also received research funding from Janssen, as well as Daiichi Sankyo and Gilead Sciences. Dr. Gurbel holds patents on platelet-function testing methods.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
ANAHEIM, CALIF. – The boxed warning recommending pharmacogenomic testing of patients receiving clopidogrel to identify reduced metabolizers seems to be playing to a largely deaf audience.
Even when handed information on whether each clopidogrel-treated patient was a poor metabolizer of the drug, treating physicians usually did not switch them to a different antiplatelet drug, ticagrelor, that would be fully effective despite the patient’s reduced-metabolizer status. And clinicians who started patients on ticagrelor did not usually switch those with a good clopidogrel-metabolizing profile to the safer drug, clopidogrel, after learning that clopidogrel would be fully effective.
“Routine reporting of pharmacogenomics test results for acute coronary syndrome patients treated with P2Y12-inhibitor therapy had an uncertain yield and little impact on P2Y12-inhibitor switching,” E. Magnus Ohman, MBBS, said at the American Heart Association scientific sessions.
The study’s design gave each participating clinician free rein on whether to prescribe clopidogrel or ticagrelor (Brilinta) initially, and switching between the drugs was possible at any time after the initial prescription. At the trial’s start, 1,704 patients (56%) were on ticagrelor and 1,333 (44%) were on clopidogrel.
Pharmacogenomic testing showed that 34% of all patients were ultrametabolizers and 38% were extensive metabolizers. Patients in either of these categories metabolize enough clopidogrel into the active form to get full benefit from the drug and derive no additional efficacy benefit from switching to another P2Y12 inhibitor, such as ticagrelor or prasugrel (Effient) – drugs unaffected by metabolizer status. Testing also identified 25% of patients as intermediate metabolizers, who carry one loss-of-function allele for the CYP2C19 gene, and 3% were reduced metabolizers, who are homozygous for loss-of-function alleles. Standard practice is not to treat intermediate or reduced metabolizers with clopidogrel because they would not get an adequate antiplatelet effect; instead, these patients are usually treated with ticagrelor or with prasugrel when it’s an option.
After receiving the results regarding the clopidogrel-metabolizing status for each patient, attending physicians switched the drugs prescribed for only 7% of all patients: 9% of patients initially on ticagrelor and 4% of those initially on clopidogrel, reported Dr. Ohman, professor of medicine at Duke University in Durham, N.C. In addition, Dr. Ohman and his associates asked each participating physician who made a switch about his or her reasons for doing so. Of the patients who switched from clopidogrel to ticagrelor, only 23 were switched because of their pharmacogenomic results; this represents fewer than half of those who switched and only 2% of all patients who took clopidogrel. Only one patient changed from ticagrelor to clopidogrel based on pharmacogenomic results, representing 0.06% of all patients on ticagrelor.
“We believed the findings do not support the utility of mandatory testing in this context, as most did not act on the information,” Dr. Ohman said.
A major reason for the inertia, Dr. Gurbel suggested, may be the absence of any compelling data proving whether there’s any effect on clinical outcomes for switching reduced metabolizers off of clopidogrel or switching good metabolizers onto it.
“We have no large-scale, prospective data supporting pharmacogenomic-based personalization” of clopidogrel treatment leading to improved outcomes, but “we need to get over that,” he said. “It’s a challenge to get funding for this.” But “the answer is not to give ticagrelor or prasugrel to everyone because then the bleeding rate is too high.”
The findings Dr. Ohman reported came from the Study to Compare the Safety of Rivaroxaban Versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Participants With Acute Coronary Syndrome (GEMINI-ACS-1), which had the primary goal of comparing the safety in acute coronary syndrome patients of a reduced dosage of rivaroxaban plus either clopidogrel or ticagrelor with the safety of aspirin plus one of these P2Y12 inhibitors. The primary endpoint was the rate of clinically significant bleeding events during a year of treatment. The study ran at 371 centers in 21 countries and showed similar bleeding rates in both treatment arms (Lancet. 2017 May 6; 389[10081]:1799-808).
The analysis also showed that patients identified as reduced metabolizers were fivefold more likely to be switched than patients identified as ultra metabolizers, and intermediate metabolizes had a 50% higher switching rate than ultra metabolizers. The rates of both ischemic and major bleeding outcomes were roughly similar across the spectrum of metabolizers, but Dr. Ohman cautioned that the trial was not designed to assess this. Dr. Gurbel urged the investigators to report on outcomes analyzed not just by metabolizer status but also by the treatment they received.
The boxed warning that clopidogrel received in 2010 regarding poor metabolizers led to “regulatory guidance” during design of the GEMINI-ACS-1 trial requiring routine pharmacogenomic testing for clopidogrel-metabolizing status, Dr. Ohman explained.
The trial was funded by Janssen and Bayer, the two companies that jointly market rivaroxaban (Xarelto). Dr. Ohman has been a consultant to Bayer and several other companies including AstraZeneca, the company that markets ticagrelor (Brilinta). He has also received research funding from Janssen, as well as Daiichi Sankyo and Gilead Sciences. Dr. Gurbel holds patents on platelet-function testing methods.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
ANAHEIM, CALIF. – The boxed warning recommending pharmacogenomic testing of patients receiving clopidogrel to identify reduced metabolizers seems to be playing to a largely deaf audience.
Even when handed information on whether each clopidogrel-treated patient was a poor metabolizer of the drug, treating physicians usually did not switch them to a different antiplatelet drug, ticagrelor, that would be fully effective despite the patient’s reduced-metabolizer status. And clinicians who started patients on ticagrelor did not usually switch those with a good clopidogrel-metabolizing profile to the safer drug, clopidogrel, after learning that clopidogrel would be fully effective.
“Routine reporting of pharmacogenomics test results for acute coronary syndrome patients treated with P2Y12-inhibitor therapy had an uncertain yield and little impact on P2Y12-inhibitor switching,” E. Magnus Ohman, MBBS, said at the American Heart Association scientific sessions.
The study’s design gave each participating clinician free rein on whether to prescribe clopidogrel or ticagrelor (Brilinta) initially, and switching between the drugs was possible at any time after the initial prescription. At the trial’s start, 1,704 patients (56%) were on ticagrelor and 1,333 (44%) were on clopidogrel.
Pharmacogenomic testing showed that 34% of all patients were ultrametabolizers and 38% were extensive metabolizers. Patients in either of these categories metabolize enough clopidogrel into the active form to get full benefit from the drug and derive no additional efficacy benefit from switching to another P2Y12 inhibitor, such as ticagrelor or prasugrel (Effient) – drugs unaffected by metabolizer status. Testing also identified 25% of patients as intermediate metabolizers, who carry one loss-of-function allele for the CYP2C19 gene, and 3% were reduced metabolizers, who are homozygous for loss-of-function alleles. Standard practice is not to treat intermediate or reduced metabolizers with clopidogrel because they would not get an adequate antiplatelet effect; instead, these patients are usually treated with ticagrelor or with prasugrel when it’s an option.
After receiving the results regarding the clopidogrel-metabolizing status for each patient, attending physicians switched the drugs prescribed for only 7% of all patients: 9% of patients initially on ticagrelor and 4% of those initially on clopidogrel, reported Dr. Ohman, professor of medicine at Duke University in Durham, N.C. In addition, Dr. Ohman and his associates asked each participating physician who made a switch about his or her reasons for doing so. Of the patients who switched from clopidogrel to ticagrelor, only 23 were switched because of their pharmacogenomic results; this represents fewer than half of those who switched and only 2% of all patients who took clopidogrel. Only one patient changed from ticagrelor to clopidogrel based on pharmacogenomic results, representing 0.06% of all patients on ticagrelor.
“We believed the findings do not support the utility of mandatory testing in this context, as most did not act on the information,” Dr. Ohman said.
A major reason for the inertia, Dr. Gurbel suggested, may be the absence of any compelling data proving whether there’s any effect on clinical outcomes for switching reduced metabolizers off of clopidogrel or switching good metabolizers onto it.
“We have no large-scale, prospective data supporting pharmacogenomic-based personalization” of clopidogrel treatment leading to improved outcomes, but “we need to get over that,” he said. “It’s a challenge to get funding for this.” But “the answer is not to give ticagrelor or prasugrel to everyone because then the bleeding rate is too high.”
The findings Dr. Ohman reported came from the Study to Compare the Safety of Rivaroxaban Versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Participants With Acute Coronary Syndrome (GEMINI-ACS-1), which had the primary goal of comparing the safety in acute coronary syndrome patients of a reduced dosage of rivaroxaban plus either clopidogrel or ticagrelor with the safety of aspirin plus one of these P2Y12 inhibitors. The primary endpoint was the rate of clinically significant bleeding events during a year of treatment. The study ran at 371 centers in 21 countries and showed similar bleeding rates in both treatment arms (Lancet. 2017 May 6; 389[10081]:1799-808).
The analysis also showed that patients identified as reduced metabolizers were fivefold more likely to be switched than patients identified as ultra metabolizers, and intermediate metabolizes had a 50% higher switching rate than ultra metabolizers. The rates of both ischemic and major bleeding outcomes were roughly similar across the spectrum of metabolizers, but Dr. Ohman cautioned that the trial was not designed to assess this. Dr. Gurbel urged the investigators to report on outcomes analyzed not just by metabolizer status but also by the treatment they received.
The boxed warning that clopidogrel received in 2010 regarding poor metabolizers led to “regulatory guidance” during design of the GEMINI-ACS-1 trial requiring routine pharmacogenomic testing for clopidogrel-metabolizing status, Dr. Ohman explained.
The trial was funded by Janssen and Bayer, the two companies that jointly market rivaroxaban (Xarelto). Dr. Ohman has been a consultant to Bayer and several other companies including AstraZeneca, the company that markets ticagrelor (Brilinta). He has also received research funding from Janssen, as well as Daiichi Sankyo and Gilead Sciences. Dr. Gurbel holds patents on platelet-function testing methods.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Physicians switched P2Y12 inhibitors for only 2% of patients on clopidogrel and only 0.06% on ticagrelor on the basis of their pharmacogenomic results.
Data source: GEMINI-ACS-1, a multicenter, prospective trial with 3,037 patients.
Disclosures: The GEMINI-ACS-1 trial was funded by Janssen and Bayer, the two companies that jointly market rivaroxaban (Xarelto). Dr. Ohman has been a consultant to Bayer and several other companies, including AstraZeneca, the company that markets ticagrelor (Brilinta). He has also received research funding from Janssen, as well as Daiichi Sankyo and Gilead Sciences. Dr. Gurbel holds patents on platelet-function testing methods.
The Pathological Underpinning of Drug-Resistant Epilepsy
Among patients with drug resistant focal epilepsy who underwent surgery, an examination of resected brain specimens revealed hippocampal sclerosis to be the most common histopathological diagnosis in adults. The same analysis, published in the New England Journal of Medicine, found children were most likely to have focal cortical dysplasia.
- The study included analysis of brain specimens from 9523 patients who underwent epilepsy surgery in 36 centers in 12 European countries over 25 years.
- About 3 of 4 patients began having seizures before age 18 years.
- 72.5% of patient had surgery as adults.
- On average, adult patients had endured epilepsy for about 20 years before having surgery while children waited 5.3 years for surgical resection.
- Hippocampal sclerosis was found in 36.4% of patients, including 88.7% of adults.
- Tumors were detected in 23.6%, most of which were ganglioglioma.
- Malformations of cortical development affected 19.8% of patients.
Blumcke I, Spreafico R, Haaker G, et al. Histopathological findings in brain tissue obtained during epilepsy surgery. N Engl J Med. 2017;377(17):1648-1656.
Among patients with drug resistant focal epilepsy who underwent surgery, an examination of resected brain specimens revealed hippocampal sclerosis to be the most common histopathological diagnosis in adults. The same analysis, published in the New England Journal of Medicine, found children were most likely to have focal cortical dysplasia.
- The study included analysis of brain specimens from 9523 patients who underwent epilepsy surgery in 36 centers in 12 European countries over 25 years.
- About 3 of 4 patients began having seizures before age 18 years.
- 72.5% of patient had surgery as adults.
- On average, adult patients had endured epilepsy for about 20 years before having surgery while children waited 5.3 years for surgical resection.
- Hippocampal sclerosis was found in 36.4% of patients, including 88.7% of adults.
- Tumors were detected in 23.6%, most of which were ganglioglioma.
- Malformations of cortical development affected 19.8% of patients.
Blumcke I, Spreafico R, Haaker G, et al. Histopathological findings in brain tissue obtained during epilepsy surgery. N Engl J Med. 2017;377(17):1648-1656.
Among patients with drug resistant focal epilepsy who underwent surgery, an examination of resected brain specimens revealed hippocampal sclerosis to be the most common histopathological diagnosis in adults. The same analysis, published in the New England Journal of Medicine, found children were most likely to have focal cortical dysplasia.
- The study included analysis of brain specimens from 9523 patients who underwent epilepsy surgery in 36 centers in 12 European countries over 25 years.
- About 3 of 4 patients began having seizures before age 18 years.
- 72.5% of patient had surgery as adults.
- On average, adult patients had endured epilepsy for about 20 years before having surgery while children waited 5.3 years for surgical resection.
- Hippocampal sclerosis was found in 36.4% of patients, including 88.7% of adults.
- Tumors were detected in 23.6%, most of which were ganglioglioma.
- Malformations of cortical development affected 19.8% of patients.
Blumcke I, Spreafico R, Haaker G, et al. Histopathological findings in brain tissue obtained during epilepsy surgery. N Engl J Med. 2017;377(17):1648-1656.
Extending Insular Glioma Resection Cuts Seizure Recurrence
In patients who have had surgical resection of an insular glioma, the wider the extent of the resection, the longer they remain free from seizures, according to a study from the department of neurological surgery at the University of California, San Francisco (UCSF).
- The analysis included 109 patients who had surgery for insular tumors from 1997 to 2015 at UCSF.
- At final follow-up, 42 patients (39%) remained seizure free.
- Increasing the extent of the resection predicted freedom from seizures.
- The analysis also revealed that performing a second resection provided even greater seizure control; 8/22 patients with recurrent seizures no longer had them after the second surgery.
- Patients who experienced a second seizure after resection were more likely to have had tumor progression.
Wang DD, Deng H, Hervey-Jumper SL, Molinaro AA, Chang EF, Berger MS. Seizure outcome after surgical resection of insular glioma. [Published online ahead of print Nov 8, 2017] Neurosurgery. doi: 10.1093/neuros/nyx486.
In patients who have had surgical resection of an insular glioma, the wider the extent of the resection, the longer they remain free from seizures, according to a study from the department of neurological surgery at the University of California, San Francisco (UCSF).
- The analysis included 109 patients who had surgery for insular tumors from 1997 to 2015 at UCSF.
- At final follow-up, 42 patients (39%) remained seizure free.
- Increasing the extent of the resection predicted freedom from seizures.
- The analysis also revealed that performing a second resection provided even greater seizure control; 8/22 patients with recurrent seizures no longer had them after the second surgery.
- Patients who experienced a second seizure after resection were more likely to have had tumor progression.
Wang DD, Deng H, Hervey-Jumper SL, Molinaro AA, Chang EF, Berger MS. Seizure outcome after surgical resection of insular glioma. [Published online ahead of print Nov 8, 2017] Neurosurgery. doi: 10.1093/neuros/nyx486.
In patients who have had surgical resection of an insular glioma, the wider the extent of the resection, the longer they remain free from seizures, according to a study from the department of neurological surgery at the University of California, San Francisco (UCSF).
- The analysis included 109 patients who had surgery for insular tumors from 1997 to 2015 at UCSF.
- At final follow-up, 42 patients (39%) remained seizure free.
- Increasing the extent of the resection predicted freedom from seizures.
- The analysis also revealed that performing a second resection provided even greater seizure control; 8/22 patients with recurrent seizures no longer had them after the second surgery.
- Patients who experienced a second seizure after resection were more likely to have had tumor progression.
Wang DD, Deng H, Hervey-Jumper SL, Molinaro AA, Chang EF, Berger MS. Seizure outcome after surgical resection of insular glioma. [Published online ahead of print Nov 8, 2017] Neurosurgery. doi: 10.1093/neuros/nyx486.
Understanding Psychopathology of PNES
Patients who experience altered responsiveness during a psychogenic nonepileptic seizures (PNES) may have some sort of psychological vulnerability suggests a recent analysis of video-EEG confirmed PNES.
- Among 77 patients with confirmed PNES, 47 (66%) were found to have altered responsiveness.
- This group was more likely to display experiential avoidance, the tendency to avoid thoughts, feelings, memories, and related internal experiences.
- A review of patients’ demographics, clinical history, and questionnaires also found patients with altered responsiveness during PNES had more affect intolerance, suggesting their inability to tolerate emotions.
- The same group presented with a family history of seizures, headaches, and loss of consciousness during traumatic brain injury.
- Researchers suggested that these patients may benefit from a treatment plan that concentrates on emotion management.
Baslet G, Tolchin B, Dworetzky BA. Altered responsiveness in psychogenic nonepileptic seizures and its implication to underlying psychopathology. Seizure. 2017;52:162-168.
Patients who experience altered responsiveness during a psychogenic nonepileptic seizures (PNES) may have some sort of psychological vulnerability suggests a recent analysis of video-EEG confirmed PNES.
- Among 77 patients with confirmed PNES, 47 (66%) were found to have altered responsiveness.
- This group was more likely to display experiential avoidance, the tendency to avoid thoughts, feelings, memories, and related internal experiences.
- A review of patients’ demographics, clinical history, and questionnaires also found patients with altered responsiveness during PNES had more affect intolerance, suggesting their inability to tolerate emotions.
- The same group presented with a family history of seizures, headaches, and loss of consciousness during traumatic brain injury.
- Researchers suggested that these patients may benefit from a treatment plan that concentrates on emotion management.
Baslet G, Tolchin B, Dworetzky BA. Altered responsiveness in psychogenic nonepileptic seizures and its implication to underlying psychopathology. Seizure. 2017;52:162-168.
Patients who experience altered responsiveness during a psychogenic nonepileptic seizures (PNES) may have some sort of psychological vulnerability suggests a recent analysis of video-EEG confirmed PNES.
- Among 77 patients with confirmed PNES, 47 (66%) were found to have altered responsiveness.
- This group was more likely to display experiential avoidance, the tendency to avoid thoughts, feelings, memories, and related internal experiences.
- A review of patients’ demographics, clinical history, and questionnaires also found patients with altered responsiveness during PNES had more affect intolerance, suggesting their inability to tolerate emotions.
- The same group presented with a family history of seizures, headaches, and loss of consciousness during traumatic brain injury.
- Researchers suggested that these patients may benefit from a treatment plan that concentrates on emotion management.
Baslet G, Tolchin B, Dworetzky BA. Altered responsiveness in psychogenic nonepileptic seizures and its implication to underlying psychopathology. Seizure. 2017;52:162-168.
Rituximab key to survival after transplant for mantle cell lymphoma
The study, which outlines the experience across a variety of different treatment patterns at City of Hope National Medical Center, Duarte, Calif., between January 1997 and November 2013, suggests a “large benefit” of adding rituximab, wrote Matthew G. Mei, MD, of the center’s department of hematology and hematopoietic cell transplantation, and his colleagues. Further, maintenance rituximab was associated with improved survival outcomes in patients with positron emission tomography (PET)-negative status at first complete remission.
The benefit of rituximab “stands out, and adds to the increasing body of evidence supporting this practice for all MCL patients after ASCT, regardless of age and frontline induction regimens,” wrote Dr. Mei and his colleagues (Biol Blood Marrow Transplant 2017 November. doi: 10.1016/j.bbmt.2017.07.006). This was the case even with improvements in early diagnosis and supportive care, and the incorporation of novel agents such as bortezomib, lenalidomide, and ibrutinib, they wrote, noting significantly better outcomes for patients who underwent ASCT after 2007.
In multivariate analysis, maintenance rituximab therapy after ASCT was the single most important factor associated with improvement in progression-free survival (relative risk [RR], .25; 95% confidence interval, .14-.44) and overall survival (RR, .17; 95% CI, .07-.38).
Positron emission tomography scans were done prior to ASCT for 133 patients; after ASCT, 105 (79%) were found to be in a PET-negative complete remission. All but one of the patients with PET-negative disease received rituximab before ASCT. For that PET-negative subset, maintenance rituximab was significantly associated with improvements in progression-free survival (RR, .20; 95% CI, .09-.43) and overall survival (RR, .17; 95% CI, .05-.59).
This study represents one of the largest single-center reports to date on MCL patients who have undergone ASCT, according to the authors. “This study also sets the stage for prospective investigation aiming at optimization of maintenance therapy following ASCT.”
Dr. Mei reported no disclosures, and senior author Lihua E. Budde, MD, PhD, reported being a member of the Lymphoma Research Foundation MCL consortium. The study was supported by research funding from the National Cancer Institute.
This study confirms the value of maintenance rituximab for a large cohort of patients with mantle cell lymphoma who have undergone high-dose chemotherapy and autologous stem cell transplantation outside of clinical trials.
The findings also affirm results of a recent phase 3 randomized trial (LyMa) suggesting that in previously untreated MCL patients who have undergone ASCT, rituximab maintenance is superior to observation in improving overall survival and progression-free survival.
However, the most interesting aspect of this study is the positron emission tomography data. Namely, the benefit of rituximab maintenance was apparent in patients regardless of whether they were in a PET-positive or PET-negative first complete remission at ASCT. “This important finding implies that the benefit of rituximab maintenance after ASCT is present for low- and high-risk MCL patients.”
Despite these confirmatory findings, the treatment landscape for MCL has changed significantly in recent years, particularly with the introduction of treatments such as ibrutinib.
In a clinical trial currently underway, the European Mantle Cell Lymphoma Network is evaluating ibrutinib as an upfront treatment for young and fit patients. Specifically, the study compares first-line ASCT and rituximab maintenance, ASCT with ibrutinib maintenance, or a transplant-free approach with ibrutinib and chemotherapy.
Unless and until the data from this study “redefine the value of ASCT in the ibrutinib era, ASCT and rituximab maintenance should be recommended as the standard treatment after ASCT for transplant-eligible patients with MCL.”
Tobias Roider, MD, and Sascha Dietrich, MD, are with the Department of Medicine V, University of Heidelberg, Germany. Their comments are in an editorial (Biol Blood Marrow Transplant 2017 November. doi: 10.1016/j.bbmt.2017.09.008). The authors reported no financial disclosures or conflicts of interest.
This study confirms the value of maintenance rituximab for a large cohort of patients with mantle cell lymphoma who have undergone high-dose chemotherapy and autologous stem cell transplantation outside of clinical trials.
The findings also affirm results of a recent phase 3 randomized trial (LyMa) suggesting that in previously untreated MCL patients who have undergone ASCT, rituximab maintenance is superior to observation in improving overall survival and progression-free survival.
However, the most interesting aspect of this study is the positron emission tomography data. Namely, the benefit of rituximab maintenance was apparent in patients regardless of whether they were in a PET-positive or PET-negative first complete remission at ASCT. “This important finding implies that the benefit of rituximab maintenance after ASCT is present for low- and high-risk MCL patients.”
Despite these confirmatory findings, the treatment landscape for MCL has changed significantly in recent years, particularly with the introduction of treatments such as ibrutinib.
In a clinical trial currently underway, the European Mantle Cell Lymphoma Network is evaluating ibrutinib as an upfront treatment for young and fit patients. Specifically, the study compares first-line ASCT and rituximab maintenance, ASCT with ibrutinib maintenance, or a transplant-free approach with ibrutinib and chemotherapy.
Unless and until the data from this study “redefine the value of ASCT in the ibrutinib era, ASCT and rituximab maintenance should be recommended as the standard treatment after ASCT for transplant-eligible patients with MCL.”
Tobias Roider, MD, and Sascha Dietrich, MD, are with the Department of Medicine V, University of Heidelberg, Germany. Their comments are in an editorial (Biol Blood Marrow Transplant 2017 November. doi: 10.1016/j.bbmt.2017.09.008). The authors reported no financial disclosures or conflicts of interest.
This study confirms the value of maintenance rituximab for a large cohort of patients with mantle cell lymphoma who have undergone high-dose chemotherapy and autologous stem cell transplantation outside of clinical trials.
The findings also affirm results of a recent phase 3 randomized trial (LyMa) suggesting that in previously untreated MCL patients who have undergone ASCT, rituximab maintenance is superior to observation in improving overall survival and progression-free survival.
However, the most interesting aspect of this study is the positron emission tomography data. Namely, the benefit of rituximab maintenance was apparent in patients regardless of whether they were in a PET-positive or PET-negative first complete remission at ASCT. “This important finding implies that the benefit of rituximab maintenance after ASCT is present for low- and high-risk MCL patients.”
Despite these confirmatory findings, the treatment landscape for MCL has changed significantly in recent years, particularly with the introduction of treatments such as ibrutinib.
In a clinical trial currently underway, the European Mantle Cell Lymphoma Network is evaluating ibrutinib as an upfront treatment for young and fit patients. Specifically, the study compares first-line ASCT and rituximab maintenance, ASCT with ibrutinib maintenance, or a transplant-free approach with ibrutinib and chemotherapy.
Unless and until the data from this study “redefine the value of ASCT in the ibrutinib era, ASCT and rituximab maintenance should be recommended as the standard treatment after ASCT for transplant-eligible patients with MCL.”
Tobias Roider, MD, and Sascha Dietrich, MD, are with the Department of Medicine V, University of Heidelberg, Germany. Their comments are in an editorial (Biol Blood Marrow Transplant 2017 November. doi: 10.1016/j.bbmt.2017.09.008). The authors reported no financial disclosures or conflicts of interest.
The study, which outlines the experience across a variety of different treatment patterns at City of Hope National Medical Center, Duarte, Calif., between January 1997 and November 2013, suggests a “large benefit” of adding rituximab, wrote Matthew G. Mei, MD, of the center’s department of hematology and hematopoietic cell transplantation, and his colleagues. Further, maintenance rituximab was associated with improved survival outcomes in patients with positron emission tomography (PET)-negative status at first complete remission.
The benefit of rituximab “stands out, and adds to the increasing body of evidence supporting this practice for all MCL patients after ASCT, regardless of age and frontline induction regimens,” wrote Dr. Mei and his colleagues (Biol Blood Marrow Transplant 2017 November. doi: 10.1016/j.bbmt.2017.07.006). This was the case even with improvements in early diagnosis and supportive care, and the incorporation of novel agents such as bortezomib, lenalidomide, and ibrutinib, they wrote, noting significantly better outcomes for patients who underwent ASCT after 2007.
In multivariate analysis, maintenance rituximab therapy after ASCT was the single most important factor associated with improvement in progression-free survival (relative risk [RR], .25; 95% confidence interval, .14-.44) and overall survival (RR, .17; 95% CI, .07-.38).
Positron emission tomography scans were done prior to ASCT for 133 patients; after ASCT, 105 (79%) were found to be in a PET-negative complete remission. All but one of the patients with PET-negative disease received rituximab before ASCT. For that PET-negative subset, maintenance rituximab was significantly associated with improvements in progression-free survival (RR, .20; 95% CI, .09-.43) and overall survival (RR, .17; 95% CI, .05-.59).
This study represents one of the largest single-center reports to date on MCL patients who have undergone ASCT, according to the authors. “This study also sets the stage for prospective investigation aiming at optimization of maintenance therapy following ASCT.”
Dr. Mei reported no disclosures, and senior author Lihua E. Budde, MD, PhD, reported being a member of the Lymphoma Research Foundation MCL consortium. The study was supported by research funding from the National Cancer Institute.
The study, which outlines the experience across a variety of different treatment patterns at City of Hope National Medical Center, Duarte, Calif., between January 1997 and November 2013, suggests a “large benefit” of adding rituximab, wrote Matthew G. Mei, MD, of the center’s department of hematology and hematopoietic cell transplantation, and his colleagues. Further, maintenance rituximab was associated with improved survival outcomes in patients with positron emission tomography (PET)-negative status at first complete remission.
The benefit of rituximab “stands out, and adds to the increasing body of evidence supporting this practice for all MCL patients after ASCT, regardless of age and frontline induction regimens,” wrote Dr. Mei and his colleagues (Biol Blood Marrow Transplant 2017 November. doi: 10.1016/j.bbmt.2017.07.006). This was the case even with improvements in early diagnosis and supportive care, and the incorporation of novel agents such as bortezomib, lenalidomide, and ibrutinib, they wrote, noting significantly better outcomes for patients who underwent ASCT after 2007.
In multivariate analysis, maintenance rituximab therapy after ASCT was the single most important factor associated with improvement in progression-free survival (relative risk [RR], .25; 95% confidence interval, .14-.44) and overall survival (RR, .17; 95% CI, .07-.38).
Positron emission tomography scans were done prior to ASCT for 133 patients; after ASCT, 105 (79%) were found to be in a PET-negative complete remission. All but one of the patients with PET-negative disease received rituximab before ASCT. For that PET-negative subset, maintenance rituximab was significantly associated with improvements in progression-free survival (RR, .20; 95% CI, .09-.43) and overall survival (RR, .17; 95% CI, .05-.59).
This study represents one of the largest single-center reports to date on MCL patients who have undergone ASCT, according to the authors. “This study also sets the stage for prospective investigation aiming at optimization of maintenance therapy following ASCT.”
Dr. Mei reported no disclosures, and senior author Lihua E. Budde, MD, PhD, reported being a member of the Lymphoma Research Foundation MCL consortium. The study was supported by research funding from the National Cancer Institute.
FROM BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Key clinical point: Over time and in many different patterns, rituximab maintenance therapy stood out as the prominent factor influencing survival in patients with mantle cell lymphoma who undergo autologous stem cell transplant.
Major finding: Maintenance rituximab was significantly associated with superior progression-free survival (relative risk, .25; 95% confidence interval, .14-.44) and overall survival (RR, .17; 95% CI, .07-.38).
Data source: Retrospective analysis of data for 191 patients with MCL who underwent ASCT at a medical center in California between January 1997 and November 2013.
Disclosures: The study was supported by research funding from the National Cancer Institute. Senior author Lihua E. Budde, MD, PhD, reported being a member of the Lymphoma Research Foundation MCL consortium.
Summary of guidelines for DMARDs for elective surgery
Clinical question: What is the best management for disease-modifying antirheumatic drugs (DMARDs) for patients with RA, ankylosing spondylitis, psoriatic arthritis, juvenile idiopathic arthritis, or systemic lupus erythematosus (SLE) undergoing elective total knee arthroplasty (TKA) or total hip arthroplasty (THA)?
Background: There are limited data in the evaluation of risks of flare with stopping DMARDs versus the risks of infection with continuing them perioperatively for elective TKA or THA, which are procedures frequently required by this patient population.
Study design: Multistep systematic literature review.
Setting: Collaboration between American College of Rheumatology and American Association of Hip and Knee Surgeons.
Synopsis: Through literature review and a requirement of 80% agreement by the panel, seven recommendations were created. Continue methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine. Biologic agents should be held with surgery scheduled at the end of dosing cycle and restarted when the wound is healed, sutures/staples are removed, and there are no signs of infection (~14 days). Tofacitinib should be held for all conditions except SLE for 1 week. For severe SLE, continue mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus but hold for 1 week for nonsevere SLE. If current dose of glucocorticoids is less than 20 mg/day, the current dose should be administered rather than administering stress-dose steroids.
Limitations include a limited number of studies conducted in the perioperative period, the existing data are based on lower dosages, and it is unknown whether results can be extrapolated to surgical procedures beyond TKA and THA. Additionally there is a need for further studies on glucocorticoid management and biologic agents.
Bottom line: Perioperative management of DMARDs is complex and understudied, but the review provides an evidence-based guide for patients undergoing TKA and THA.
Citation: Goodman SM, Springer B, Gordon G, et. al. 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. Arthritis Care Res. 2017 Aug;69(8):1111-24.
Dr. Kochar is hospitalist and assistant professor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
Clinical question: What is the best management for disease-modifying antirheumatic drugs (DMARDs) for patients with RA, ankylosing spondylitis, psoriatic arthritis, juvenile idiopathic arthritis, or systemic lupus erythematosus (SLE) undergoing elective total knee arthroplasty (TKA) or total hip arthroplasty (THA)?
Background: There are limited data in the evaluation of risks of flare with stopping DMARDs versus the risks of infection with continuing them perioperatively for elective TKA or THA, which are procedures frequently required by this patient population.
Study design: Multistep systematic literature review.
Setting: Collaboration between American College of Rheumatology and American Association of Hip and Knee Surgeons.
Synopsis: Through literature review and a requirement of 80% agreement by the panel, seven recommendations were created. Continue methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine. Biologic agents should be held with surgery scheduled at the end of dosing cycle and restarted when the wound is healed, sutures/staples are removed, and there are no signs of infection (~14 days). Tofacitinib should be held for all conditions except SLE for 1 week. For severe SLE, continue mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus but hold for 1 week for nonsevere SLE. If current dose of glucocorticoids is less than 20 mg/day, the current dose should be administered rather than administering stress-dose steroids.
Limitations include a limited number of studies conducted in the perioperative period, the existing data are based on lower dosages, and it is unknown whether results can be extrapolated to surgical procedures beyond TKA and THA. Additionally there is a need for further studies on glucocorticoid management and biologic agents.
Bottom line: Perioperative management of DMARDs is complex and understudied, but the review provides an evidence-based guide for patients undergoing TKA and THA.
Citation: Goodman SM, Springer B, Gordon G, et. al. 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. Arthritis Care Res. 2017 Aug;69(8):1111-24.
Dr. Kochar is hospitalist and assistant professor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
Clinical question: What is the best management for disease-modifying antirheumatic drugs (DMARDs) for patients with RA, ankylosing spondylitis, psoriatic arthritis, juvenile idiopathic arthritis, or systemic lupus erythematosus (SLE) undergoing elective total knee arthroplasty (TKA) or total hip arthroplasty (THA)?
Background: There are limited data in the evaluation of risks of flare with stopping DMARDs versus the risks of infection with continuing them perioperatively for elective TKA or THA, which are procedures frequently required by this patient population.
Study design: Multistep systematic literature review.
Setting: Collaboration between American College of Rheumatology and American Association of Hip and Knee Surgeons.
Synopsis: Through literature review and a requirement of 80% agreement by the panel, seven recommendations were created. Continue methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine. Biologic agents should be held with surgery scheduled at the end of dosing cycle and restarted when the wound is healed, sutures/staples are removed, and there are no signs of infection (~14 days). Tofacitinib should be held for all conditions except SLE for 1 week. For severe SLE, continue mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus but hold for 1 week for nonsevere SLE. If current dose of glucocorticoids is less than 20 mg/day, the current dose should be administered rather than administering stress-dose steroids.
Limitations include a limited number of studies conducted in the perioperative period, the existing data are based on lower dosages, and it is unknown whether results can be extrapolated to surgical procedures beyond TKA and THA. Additionally there is a need for further studies on glucocorticoid management and biologic agents.
Bottom line: Perioperative management of DMARDs is complex and understudied, but the review provides an evidence-based guide for patients undergoing TKA and THA.
Citation: Goodman SM, Springer B, Gordon G, et. al. 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. Arthritis Care Res. 2017 Aug;69(8):1111-24.
Dr. Kochar is hospitalist and assistant professor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
VIDEO: Outpatient hysterectomies offer advantages for surgeons, patients
NATIONAL HARBOR, MD. – Moving hysterectomy and advanced gynecologic procedures to the ambulatory surgical environment is better for patients, surgeons, and the health care system, Richard B. Rosenfield, MD, who is in private practice in Portland, Ore., said at the AAGL Global Congress.
“We’ve been basically proving this model over the last decade by performing advanced laparoscopic surgery in the outpatient environment, and we do this for a number of reasons,” Dr. Rosenfield said in an interview. “The patients get to go home the same day, which they typically enjoy, we avoid the hospital-acquired infections, which is great, and in addition to that, the physicians tend to really appreciate the efficiency of an outpatient center.”
But with the focus on value-based payment under federal health programs, there should also be a greater focus on getting more high-volume surgeons to perform their procedures, he said. The idea is to lower the hospital readmissions, complications, and infections that could arise during procedures by less experienced surgeons and redirect the cost savings toward payments for surgeons with better outcomes, Dr. Rosenfield said. But this should be coupled with training and mentoring for lower-volume surgeons, he said.
Dr. Rosenfield reported having no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
NATIONAL HARBOR, MD. – Moving hysterectomy and advanced gynecologic procedures to the ambulatory surgical environment is better for patients, surgeons, and the health care system, Richard B. Rosenfield, MD, who is in private practice in Portland, Ore., said at the AAGL Global Congress.
“We’ve been basically proving this model over the last decade by performing advanced laparoscopic surgery in the outpatient environment, and we do this for a number of reasons,” Dr. Rosenfield said in an interview. “The patients get to go home the same day, which they typically enjoy, we avoid the hospital-acquired infections, which is great, and in addition to that, the physicians tend to really appreciate the efficiency of an outpatient center.”
But with the focus on value-based payment under federal health programs, there should also be a greater focus on getting more high-volume surgeons to perform their procedures, he said. The idea is to lower the hospital readmissions, complications, and infections that could arise during procedures by less experienced surgeons and redirect the cost savings toward payments for surgeons with better outcomes, Dr. Rosenfield said. But this should be coupled with training and mentoring for lower-volume surgeons, he said.
Dr. Rosenfield reported having no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
NATIONAL HARBOR, MD. – Moving hysterectomy and advanced gynecologic procedures to the ambulatory surgical environment is better for patients, surgeons, and the health care system, Richard B. Rosenfield, MD, who is in private practice in Portland, Ore., said at the AAGL Global Congress.
“We’ve been basically proving this model over the last decade by performing advanced laparoscopic surgery in the outpatient environment, and we do this for a number of reasons,” Dr. Rosenfield said in an interview. “The patients get to go home the same day, which they typically enjoy, we avoid the hospital-acquired infections, which is great, and in addition to that, the physicians tend to really appreciate the efficiency of an outpatient center.”
But with the focus on value-based payment under federal health programs, there should also be a greater focus on getting more high-volume surgeons to perform their procedures, he said. The idea is to lower the hospital readmissions, complications, and infections that could arise during procedures by less experienced surgeons and redirect the cost savings toward payments for surgeons with better outcomes, Dr. Rosenfield said. But this should be coupled with training and mentoring for lower-volume surgeons, he said.
Dr. Rosenfield reported having no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
AT AAGL 2017
Is It Safe to Manage Thyroid Cancer by Surveillance?
Research groups have suggested that small papillary thyroid cancers (PTCs) (< 2 cm) have been overdiagnosed and overtreated. But then the question is how to manage patients with small PTCs and the even smaller (< 1 cm) papillary microcarcinomas (PMCs).
In 1993, physicians from Kuma Hospital, Kobe, Japan, initiated an active surveillance trial for patients with low-risk PMCs without worrisome features. They observed that only a minority of patients showed disease progression, and those patients were successfully treated with rescue surgery. The Cancer Institute Hospital in Tokyo reported similar promising data from a trial 2 years later. The 2015 American Thyroid Association guidelines now acknowledge that active surveillance can be an alternative to immediate surgery in patients with low-risk PMCs.
At Kuma Hospital, the researchers noted that over time disease progression differed according to patient age. Using data on 1,211 patients in their surveillance program from 1993 to 2011, they estimated the lifetime probabilities of disease progression during active surveillance.
The estimated trend curves of disease progression “varied markedly,” the researchers found, depending on the patient’s age at presentation. Patients in their 20s and 30s had a steep increase for the first 10 to 20 years, with a gradual increase thereafter. Patients in their 40s or older showed a milder increase. The estimated lifetime probability of disease progression fell with each decade of age at presentation.
Related: Hashimoto’s Thyroiditis and Lymphoma
The researchers propose that surveillance be continued for the patient’s lifetime because tumors progress in a “small but noteworthy” percentage of patients. When patients with low-risk PMCs are treated surgically at presentation, they should still be followed after the surgery. Two- thirds of the patients who underwent immediate surgery still needed l-thyroxine and most likely will for their lifetime, the researchers note. However, PMCs that may progress after the 10-year point of active surveillance could be expected to have a very mild progressive nature, the researchers conclude, and the outcome of surgery should be excellent.
Source:
Miyauchi A, Kudo T, Ito Y, et al. Surgery. 2017. http://dx.doi.org/10.1016/j.surg.2017.03.028. In press.
Research groups have suggested that small papillary thyroid cancers (PTCs) (< 2 cm) have been overdiagnosed and overtreated. But then the question is how to manage patients with small PTCs and the even smaller (< 1 cm) papillary microcarcinomas (PMCs).
In 1993, physicians from Kuma Hospital, Kobe, Japan, initiated an active surveillance trial for patients with low-risk PMCs without worrisome features. They observed that only a minority of patients showed disease progression, and those patients were successfully treated with rescue surgery. The Cancer Institute Hospital in Tokyo reported similar promising data from a trial 2 years later. The 2015 American Thyroid Association guidelines now acknowledge that active surveillance can be an alternative to immediate surgery in patients with low-risk PMCs.
At Kuma Hospital, the researchers noted that over time disease progression differed according to patient age. Using data on 1,211 patients in their surveillance program from 1993 to 2011, they estimated the lifetime probabilities of disease progression during active surveillance.
The estimated trend curves of disease progression “varied markedly,” the researchers found, depending on the patient’s age at presentation. Patients in their 20s and 30s had a steep increase for the first 10 to 20 years, with a gradual increase thereafter. Patients in their 40s or older showed a milder increase. The estimated lifetime probability of disease progression fell with each decade of age at presentation.
Related: Hashimoto’s Thyroiditis and Lymphoma
The researchers propose that surveillance be continued for the patient’s lifetime because tumors progress in a “small but noteworthy” percentage of patients. When patients with low-risk PMCs are treated surgically at presentation, they should still be followed after the surgery. Two- thirds of the patients who underwent immediate surgery still needed l-thyroxine and most likely will for their lifetime, the researchers note. However, PMCs that may progress after the 10-year point of active surveillance could be expected to have a very mild progressive nature, the researchers conclude, and the outcome of surgery should be excellent.
Source:
Miyauchi A, Kudo T, Ito Y, et al. Surgery. 2017. http://dx.doi.org/10.1016/j.surg.2017.03.028. In press.
Research groups have suggested that small papillary thyroid cancers (PTCs) (< 2 cm) have been overdiagnosed and overtreated. But then the question is how to manage patients with small PTCs and the even smaller (< 1 cm) papillary microcarcinomas (PMCs).
In 1993, physicians from Kuma Hospital, Kobe, Japan, initiated an active surveillance trial for patients with low-risk PMCs without worrisome features. They observed that only a minority of patients showed disease progression, and those patients were successfully treated with rescue surgery. The Cancer Institute Hospital in Tokyo reported similar promising data from a trial 2 years later. The 2015 American Thyroid Association guidelines now acknowledge that active surveillance can be an alternative to immediate surgery in patients with low-risk PMCs.
At Kuma Hospital, the researchers noted that over time disease progression differed according to patient age. Using data on 1,211 patients in their surveillance program from 1993 to 2011, they estimated the lifetime probabilities of disease progression during active surveillance.
The estimated trend curves of disease progression “varied markedly,” the researchers found, depending on the patient’s age at presentation. Patients in their 20s and 30s had a steep increase for the first 10 to 20 years, with a gradual increase thereafter. Patients in their 40s or older showed a milder increase. The estimated lifetime probability of disease progression fell with each decade of age at presentation.
Related: Hashimoto’s Thyroiditis and Lymphoma
The researchers propose that surveillance be continued for the patient’s lifetime because tumors progress in a “small but noteworthy” percentage of patients. When patients with low-risk PMCs are treated surgically at presentation, they should still be followed after the surgery. Two- thirds of the patients who underwent immediate surgery still needed l-thyroxine and most likely will for their lifetime, the researchers note. However, PMCs that may progress after the 10-year point of active surveillance could be expected to have a very mild progressive nature, the researchers conclude, and the outcome of surgery should be excellent.
Source:
Miyauchi A, Kudo T, Ito Y, et al. Surgery. 2017. http://dx.doi.org/10.1016/j.surg.2017.03.028. In press.
Rigosertib produces better OS in MDS than tAML
Rigosertib has demonstrated activity and tolerability in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia transformed from MDS (tAML), according to researchers.
In a phase 1/2 study, rigosertib produced responses in a quarter of MDS/tAML patients and enabled stable disease in another quarter.
Overall survival (OS) was about a year longer for responders than for non-responders.
MDS patients were more likely to respond to rigosertib and therefore enjoyed longer OS than tAML patients.
Overall, rigosertib was considered well-tolerated. There were no treatment-related deaths, though 18% of patients experienced treatment-related serious adverse events (AEs).
Lewis Silverman, MD, of Icahn School of Medicine at Mount Sinai in New York, New York, and his colleagues described these results in Leukemia Research.
The study was sponsored by Onconova Therapeutics, Inc., the company developing rigosertib.
Rigosertib is an inhibitor of Ras-effector pathways that interacts with the Ras binding domains common to several signaling proteins, including Raf and PI3 kinase.
Dr Silverman and his colleagues tested intravenous rigosertib in a dose-escalation, phase 1/2 study of 22 patients. Patients had tAML (n=13), high-risk MDS (n=6), intermediate-2-risk MDS (n=2), or chronic myelomonocytic leukemia (n=1).
All patients had relapsed or were refractory to standard therapy and had no approved options for second-line therapies. The patients’ median age was 78 (range, 59-84), and 90% were male.
Patients received 3- to 7-day continuous infusions of rigosertib at doses ranging from 650 mg/m2/day to 1700 mg/m2/day in 14-day cycles.
The mean number of treatment cycles was 5.6 ± 5.8 (range, 1-23). The maximum tolerated dose of rigosertib was 1700 mg/m2/day, and the recommended phase 2 dose was 1375 mg/m2/day.
Safety
All patients had at least 1 AE. The most common AEs of any grade were fatigue (n=16, 73%), diarrhea (n=12, 55%), pyrexia (n=12, 55%), dyspnea (n=11, 50%), insomnia (n=11, 50%), anemia (n=10, 46%), constipation (n=9, 41%), nausea (n=9, 41%), cough (n=9, 41%), and decreased appetite (n=9, 41%).
The most common grade 3 or higher AEs were anemia (n=9, 41%), thrombocytopenia (n=5, 23%), pneumonia (n=5, 23%), hypoglycemia (n=4, 18%), hyponatremia (n=4, 18%), and hypophosphatemia (n=4, 18%).
Four patients (18%) had treatment-related serious AEs. This included hematuria and pollakiuria (n=1), dysuria and pollakiuria (n=1), asthenia (n=1), and dyspnea (n=1). Thirteen patients (59%) stopped treatment due to AEs.
Ten patients, who remained on study from 1 to 19 months, died within 30 days of stopping rigosertib. There were no treatment-related deaths.
Efficacy
Nineteen patients were evaluable for efficacy.
Five patients responded to treatment. Four patients with MDS had a marrow complete response, and 1 with tAML had a marrow partial response. Two of the patients with marrow complete response also had hematologic improvements.
Five patients had stable disease, 3 with MDS and 2 with tAML.
The median OS was 15.7 months for responders and 2.0 months for non-responders (P=0.0070). The median OS was 12.0 months for MDS patients and 2.0 months for tAML patients (P<0.0001).
“The publication of results from this historical study provides support of the relationship between bone marrow blast response and improvement in overall survival in this group of patients with MDS and acute myeloid leukemia for whom no FDA-approved treatments are currently available,” said Ramesh Kumar, president and chief executive officer of Onconova Therapeutics, Inc.
He added that these data are “fundamental to the rationale” of ongoing studies of rigosertib in high-risk MDS patients. 
Rigosertib has demonstrated activity and tolerability in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia transformed from MDS (tAML), according to researchers.
In a phase 1/2 study, rigosertib produced responses in a quarter of MDS/tAML patients and enabled stable disease in another quarter.
Overall survival (OS) was about a year longer for responders than for non-responders.
MDS patients were more likely to respond to rigosertib and therefore enjoyed longer OS than tAML patients.
Overall, rigosertib was considered well-tolerated. There were no treatment-related deaths, though 18% of patients experienced treatment-related serious adverse events (AEs).
Lewis Silverman, MD, of Icahn School of Medicine at Mount Sinai in New York, New York, and his colleagues described these results in Leukemia Research.
The study was sponsored by Onconova Therapeutics, Inc., the company developing rigosertib.
Rigosertib is an inhibitor of Ras-effector pathways that interacts with the Ras binding domains common to several signaling proteins, including Raf and PI3 kinase.
Dr Silverman and his colleagues tested intravenous rigosertib in a dose-escalation, phase 1/2 study of 22 patients. Patients had tAML (n=13), high-risk MDS (n=6), intermediate-2-risk MDS (n=2), or chronic myelomonocytic leukemia (n=1).
All patients had relapsed or were refractory to standard therapy and had no approved options for second-line therapies. The patients’ median age was 78 (range, 59-84), and 90% were male.
Patients received 3- to 7-day continuous infusions of rigosertib at doses ranging from 650 mg/m2/day to 1700 mg/m2/day in 14-day cycles.
The mean number of treatment cycles was 5.6 ± 5.8 (range, 1-23). The maximum tolerated dose of rigosertib was 1700 mg/m2/day, and the recommended phase 2 dose was 1375 mg/m2/day.
Safety
All patients had at least 1 AE. The most common AEs of any grade were fatigue (n=16, 73%), diarrhea (n=12, 55%), pyrexia (n=12, 55%), dyspnea (n=11, 50%), insomnia (n=11, 50%), anemia (n=10, 46%), constipation (n=9, 41%), nausea (n=9, 41%), cough (n=9, 41%), and decreased appetite (n=9, 41%).
The most common grade 3 or higher AEs were anemia (n=9, 41%), thrombocytopenia (n=5, 23%), pneumonia (n=5, 23%), hypoglycemia (n=4, 18%), hyponatremia (n=4, 18%), and hypophosphatemia (n=4, 18%).
Four patients (18%) had treatment-related serious AEs. This included hematuria and pollakiuria (n=1), dysuria and pollakiuria (n=1), asthenia (n=1), and dyspnea (n=1). Thirteen patients (59%) stopped treatment due to AEs.
Ten patients, who remained on study from 1 to 19 months, died within 30 days of stopping rigosertib. There were no treatment-related deaths.
Efficacy
Nineteen patients were evaluable for efficacy.
Five patients responded to treatment. Four patients with MDS had a marrow complete response, and 1 with tAML had a marrow partial response. Two of the patients with marrow complete response also had hematologic improvements.
Five patients had stable disease, 3 with MDS and 2 with tAML.
The median OS was 15.7 months for responders and 2.0 months for non-responders (P=0.0070). The median OS was 12.0 months for MDS patients and 2.0 months for tAML patients (P<0.0001).
“The publication of results from this historical study provides support of the relationship between bone marrow blast response and improvement in overall survival in this group of patients with MDS and acute myeloid leukemia for whom no FDA-approved treatments are currently available,” said Ramesh Kumar, president and chief executive officer of Onconova Therapeutics, Inc.
He added that these data are “fundamental to the rationale” of ongoing studies of rigosertib in high-risk MDS patients.
Rigosertib has demonstrated activity and tolerability in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia transformed from MDS (tAML), according to researchers.
In a phase 1/2 study, rigosertib produced responses in a quarter of MDS/tAML patients and enabled stable disease in another quarter.
Overall survival (OS) was about a year longer for responders than for non-responders.
MDS patients were more likely to respond to rigosertib and therefore enjoyed longer OS than tAML patients.
Overall, rigosertib was considered well-tolerated. There were no treatment-related deaths, though 18% of patients experienced treatment-related serious adverse events (AEs).
Lewis Silverman, MD, of Icahn School of Medicine at Mount Sinai in New York, New York, and his colleagues described these results in Leukemia Research.
The study was sponsored by Onconova Therapeutics, Inc., the company developing rigosertib.
Rigosertib is an inhibitor of Ras-effector pathways that interacts with the Ras binding domains common to several signaling proteins, including Raf and PI3 kinase.
Dr Silverman and his colleagues tested intravenous rigosertib in a dose-escalation, phase 1/2 study of 22 patients. Patients had tAML (n=13), high-risk MDS (n=6), intermediate-2-risk MDS (n=2), or chronic myelomonocytic leukemia (n=1).
All patients had relapsed or were refractory to standard therapy and had no approved options for second-line therapies. The patients’ median age was 78 (range, 59-84), and 90% were male.
Patients received 3- to 7-day continuous infusions of rigosertib at doses ranging from 650 mg/m2/day to 1700 mg/m2/day in 14-day cycles.
The mean number of treatment cycles was 5.6 ± 5.8 (range, 1-23). The maximum tolerated dose of rigosertib was 1700 mg/m2/day, and the recommended phase 2 dose was 1375 mg/m2/day.
Safety
All patients had at least 1 AE. The most common AEs of any grade were fatigue (n=16, 73%), diarrhea (n=12, 55%), pyrexia (n=12, 55%), dyspnea (n=11, 50%), insomnia (n=11, 50%), anemia (n=10, 46%), constipation (n=9, 41%), nausea (n=9, 41%), cough (n=9, 41%), and decreased appetite (n=9, 41%).
The most common grade 3 or higher AEs were anemia (n=9, 41%), thrombocytopenia (n=5, 23%), pneumonia (n=5, 23%), hypoglycemia (n=4, 18%), hyponatremia (n=4, 18%), and hypophosphatemia (n=4, 18%).
Four patients (18%) had treatment-related serious AEs. This included hematuria and pollakiuria (n=1), dysuria and pollakiuria (n=1), asthenia (n=1), and dyspnea (n=1). Thirteen patients (59%) stopped treatment due to AEs.
Ten patients, who remained on study from 1 to 19 months, died within 30 days of stopping rigosertib. There were no treatment-related deaths.
Efficacy
Nineteen patients were evaluable for efficacy.
Five patients responded to treatment. Four patients with MDS had a marrow complete response, and 1 with tAML had a marrow partial response. Two of the patients with marrow complete response also had hematologic improvements.
Five patients had stable disease, 3 with MDS and 2 with tAML.
The median OS was 15.7 months for responders and 2.0 months for non-responders (P=0.0070). The median OS was 12.0 months for MDS patients and 2.0 months for tAML patients (P<0.0001).
“The publication of results from this historical study provides support of the relationship between bone marrow blast response and improvement in overall survival in this group of patients with MDS and acute myeloid leukemia for whom no FDA-approved treatments are currently available,” said Ramesh Kumar, president and chief executive officer of Onconova Therapeutics, Inc.
He added that these data are “fundamental to the rationale” of ongoing studies of rigosertib in high-risk MDS patients.
Drug can treat severely ill SCD patients, case suggests
ATLANTA—Results of a case study suggest voxelotor (previously GBT440) can be effective in severely ill patients with sickle cell disease (SCD).
Voxelotor is currently under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older.
A 67-year-old male SCD patient could not participate in the study due to severe, transfusion-refractory anemia, so he received voxelotor via compassionate access.
This patient’s results were presented at the Sickle Cell Disease Association of America (SCDAA) 45th Annual National Convention.
The patient had the HbSS genotype with severe anemia that was refractory to transfusion. The patient had developed red cell antibodies after receiving multiple transfusions, and these antibodies prevented further transfusions to correct his anemia.
The patient also had moderate chronic obstructive pulmonary disease requiring supplemental oxygen therapy, recurrent and frequent pain exacerbations, extreme fatigue, and clinical depression.
The patient received voxelotor at 900 mg orally once daily. He responded to the treatment within 1 to 2 weeks, experiencing improvements in pain, fatigue, and overall mental health (as measured by the Patient Health Quality-9 score).
The patient’s hemoglobin levels rose quickly, to approximately 1.5 g/dL above baseline, with a sustained increase over 66 weeks in the range of 1 to 1.5 g/dL.
There were reductions in reticulocyte count and bilirubin as well, both consistent with diminished hemolysis.
The patient’s blood oxygen saturation improved on the standard walk test, from 86 mmHg at baseline to 96 mmHg at 65 weeks, and he discontinued continuous oxygen supplementation.
The patient has not been hospitalized due to sickle cell pain since he started taking voxelotor.
He has experienced a treatment-related side effect—grade 2 diarrhea. This occurred 9 weeks after he started voxelotor treatment, when the dose was increased to 1500 mg daily, but it resolved upon return to 900 mg. The patient has experienced no other treatment-related side effects.
Clinical and laboratory improvements have continued for more than 17 months, and the patient remains on treatment today under compassionate use access.
“This severely ill SCD patient’s clinical response, assessed by both objective and subjective measures, illustrates why we are encouraged by the voxelotor program,” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics, the company developing voxelotor.
“We plan to present additional data from other severely ill sickle cell patients who have received voxelotor via single-patient compassionate access treatment at FSCDR [the Foundation for Sickle Cell Disease Research] at an upcoming medical meeting. Of course, controlled clinical trials are needed to assess the efficacy and safety of voxelotor in SCD patients, including those with severe anemia.”
ATLANTA—Results of a case study suggest voxelotor (previously GBT440) can be effective in severely ill patients with sickle cell disease (SCD).
Voxelotor is currently under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older.
A 67-year-old male SCD patient could not participate in the study due to severe, transfusion-refractory anemia, so he received voxelotor via compassionate access.
This patient’s results were presented at the Sickle Cell Disease Association of America (SCDAA) 45th Annual National Convention.
The patient had the HbSS genotype with severe anemia that was refractory to transfusion. The patient had developed red cell antibodies after receiving multiple transfusions, and these antibodies prevented further transfusions to correct his anemia.
The patient also had moderate chronic obstructive pulmonary disease requiring supplemental oxygen therapy, recurrent and frequent pain exacerbations, extreme fatigue, and clinical depression.
The patient received voxelotor at 900 mg orally once daily. He responded to the treatment within 1 to 2 weeks, experiencing improvements in pain, fatigue, and overall mental health (as measured by the Patient Health Quality-9 score).
The patient’s hemoglobin levels rose quickly, to approximately 1.5 g/dL above baseline, with a sustained increase over 66 weeks in the range of 1 to 1.5 g/dL.
There were reductions in reticulocyte count and bilirubin as well, both consistent with diminished hemolysis.
The patient’s blood oxygen saturation improved on the standard walk test, from 86 mmHg at baseline to 96 mmHg at 65 weeks, and he discontinued continuous oxygen supplementation.
The patient has not been hospitalized due to sickle cell pain since he started taking voxelotor.
He has experienced a treatment-related side effect—grade 2 diarrhea. This occurred 9 weeks after he started voxelotor treatment, when the dose was increased to 1500 mg daily, but it resolved upon return to 900 mg. The patient has experienced no other treatment-related side effects.
Clinical and laboratory improvements have continued for more than 17 months, and the patient remains on treatment today under compassionate use access.
“This severely ill SCD patient’s clinical response, assessed by both objective and subjective measures, illustrates why we are encouraged by the voxelotor program,” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics, the company developing voxelotor.
“We plan to present additional data from other severely ill sickle cell patients who have received voxelotor via single-patient compassionate access treatment at FSCDR [the Foundation for Sickle Cell Disease Research] at an upcoming medical meeting. Of course, controlled clinical trials are needed to assess the efficacy and safety of voxelotor in SCD patients, including those with severe anemia.”
ATLANTA—Results of a case study suggest voxelotor (previously GBT440) can be effective in severely ill patients with sickle cell disease (SCD).
Voxelotor is currently under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older.
A 67-year-old male SCD patient could not participate in the study due to severe, transfusion-refractory anemia, so he received voxelotor via compassionate access.
This patient’s results were presented at the Sickle Cell Disease Association of America (SCDAA) 45th Annual National Convention.
The patient had the HbSS genotype with severe anemia that was refractory to transfusion. The patient had developed red cell antibodies after receiving multiple transfusions, and these antibodies prevented further transfusions to correct his anemia.
The patient also had moderate chronic obstructive pulmonary disease requiring supplemental oxygen therapy, recurrent and frequent pain exacerbations, extreme fatigue, and clinical depression.
The patient received voxelotor at 900 mg orally once daily. He responded to the treatment within 1 to 2 weeks, experiencing improvements in pain, fatigue, and overall mental health (as measured by the Patient Health Quality-9 score).
The patient’s hemoglobin levels rose quickly, to approximately 1.5 g/dL above baseline, with a sustained increase over 66 weeks in the range of 1 to 1.5 g/dL.
There were reductions in reticulocyte count and bilirubin as well, both consistent with diminished hemolysis.
The patient’s blood oxygen saturation improved on the standard walk test, from 86 mmHg at baseline to 96 mmHg at 65 weeks, and he discontinued continuous oxygen supplementation.
The patient has not been hospitalized due to sickle cell pain since he started taking voxelotor.
He has experienced a treatment-related side effect—grade 2 diarrhea. This occurred 9 weeks after he started voxelotor treatment, when the dose was increased to 1500 mg daily, but it resolved upon return to 900 mg. The patient has experienced no other treatment-related side effects.
Clinical and laboratory improvements have continued for more than 17 months, and the patient remains on treatment today under compassionate use access.
“This severely ill SCD patient’s clinical response, assessed by both objective and subjective measures, illustrates why we are encouraged by the voxelotor program,” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics, the company developing voxelotor.
“We plan to present additional data from other severely ill sickle cell patients who have received voxelotor via single-patient compassionate access treatment at FSCDR [the Foundation for Sickle Cell Disease Research] at an upcoming medical meeting. Of course, controlled clinical trials are needed to assess the efficacy and safety of voxelotor in SCD patients, including those with severe anemia.”