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Consolidation can improve PFS in HL
Consolidation therapy with brentuximab vedotin can improve progression-free survival (PFS) for Hodgkin lymphoma (HL) patients who have undergone a transplant, according to a phase 3 study.
The trial, known as AETHERA, is a comparison of single-agent brentuximab vedotin to placebo in patients with HL who were at risk of relapse following autologous stem cell transplant (ASCT).
Brentuximab vedotin conferred a 75% improvement in PFS over placebo.
However, there was no significant difference in overall survival between the 2 treatment arms.
These results were recently announced by Seattle Genetics Inc. and Takeda Pharmaceutical Company Limited, the companies developing brentuximab vedotin (Adcetris).
The companies said more complete results from AETHERA will be presented at the 2014 ASH Annual Meeting in December.
AETHERA is a randomized, double-blind, placebo-controlled study designed to evaluate the potential of brentuximab vedotin to extend PFS post-ASCT in patients with HL who have at least one risk factor for progression. In addition to the primary endpoint of PFS, secondary endpoints included overall survival, safety, and tolerability.
Patients were eligible if they had risk factors for residual HL, defined as a history of refractory HL, those who relapse or progress within a year of receiving frontline chemotherapy, and/or those who have disease outside of the lymph nodes at the time of pre-ASCT relapse.
The study included 329 patients who received brentuximab vedotin or placebo every 3 weeks for up to a year.
The researchers assessed PFS a minimum of 2 years after the initiation of treatment for all patients. There was a significant improvement in PFS with brentuximab vedotin compared to placebo (hazard ratio=0.57; P=0.001).
However, a prespecified interim analysis of overall survival showed no significant difference between the treatment arms.
Patients in both arms who experienced progression received a variety of subsequent therapies. Most patients on the placebo arm received brentuximab vedotin after progression.
A further analysis of overall survival is planned in 2016. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.
“We anticipate reporting more complete AETHERA data at the ASH Annual Meeting in December and intend to submit a supplemental Biologics License Application to the FDA in 2015 for approval in this setting,” said Clay B. Siegall, PhD, President and Chief Executive Officer of Seattle Genetics.
The FDA has already granted brentuximab vedotin accelerated approval to treat HL patients after ASCT failure or after the failure of at least 2 prior multiagent chemotherapy regimens in patients who are not ASCT candidates. The FDA also granted the drug accelerated approval to treat systemic anaplastic large cell lymphoma after the failure of at least 1 prior multiagent chemotherapy regimen.
The European Commission granted brentuximab vedotin conditional marketing authorization for the same indications. In both cases, the drug can gain full, traditional approval once studies have shown it confers a clinical benefit.
Brentuximab vedotin has a boxed warning detailing the risk of progressive multifocal leukoencephalopathy associated with use of the drug. The drug has also been shown to pose a risk of pulmonary toxicity when combined with bleomycin. 
Consolidation therapy with brentuximab vedotin can improve progression-free survival (PFS) for Hodgkin lymphoma (HL) patients who have undergone a transplant, according to a phase 3 study.
The trial, known as AETHERA, is a comparison of single-agent brentuximab vedotin to placebo in patients with HL who were at risk of relapse following autologous stem cell transplant (ASCT).
Brentuximab vedotin conferred a 75% improvement in PFS over placebo.
However, there was no significant difference in overall survival between the 2 treatment arms.
These results were recently announced by Seattle Genetics Inc. and Takeda Pharmaceutical Company Limited, the companies developing brentuximab vedotin (Adcetris).
The companies said more complete results from AETHERA will be presented at the 2014 ASH Annual Meeting in December.
AETHERA is a randomized, double-blind, placebo-controlled study designed to evaluate the potential of brentuximab vedotin to extend PFS post-ASCT in patients with HL who have at least one risk factor for progression. In addition to the primary endpoint of PFS, secondary endpoints included overall survival, safety, and tolerability.
Patients were eligible if they had risk factors for residual HL, defined as a history of refractory HL, those who relapse or progress within a year of receiving frontline chemotherapy, and/or those who have disease outside of the lymph nodes at the time of pre-ASCT relapse.
The study included 329 patients who received brentuximab vedotin or placebo every 3 weeks for up to a year.
The researchers assessed PFS a minimum of 2 years after the initiation of treatment for all patients. There was a significant improvement in PFS with brentuximab vedotin compared to placebo (hazard ratio=0.57; P=0.001).
However, a prespecified interim analysis of overall survival showed no significant difference between the treatment arms.
Patients in both arms who experienced progression received a variety of subsequent therapies. Most patients on the placebo arm received brentuximab vedotin after progression.
A further analysis of overall survival is planned in 2016. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.
“We anticipate reporting more complete AETHERA data at the ASH Annual Meeting in December and intend to submit a supplemental Biologics License Application to the FDA in 2015 for approval in this setting,” said Clay B. Siegall, PhD, President and Chief Executive Officer of Seattle Genetics.
The FDA has already granted brentuximab vedotin accelerated approval to treat HL patients after ASCT failure or after the failure of at least 2 prior multiagent chemotherapy regimens in patients who are not ASCT candidates. The FDA also granted the drug accelerated approval to treat systemic anaplastic large cell lymphoma after the failure of at least 1 prior multiagent chemotherapy regimen.
The European Commission granted brentuximab vedotin conditional marketing authorization for the same indications. In both cases, the drug can gain full, traditional approval once studies have shown it confers a clinical benefit.
Brentuximab vedotin has a boxed warning detailing the risk of progressive multifocal leukoencephalopathy associated with use of the drug. The drug has also been shown to pose a risk of pulmonary toxicity when combined with bleomycin.
Consolidation therapy with brentuximab vedotin can improve progression-free survival (PFS) for Hodgkin lymphoma (HL) patients who have undergone a transplant, according to a phase 3 study.
The trial, known as AETHERA, is a comparison of single-agent brentuximab vedotin to placebo in patients with HL who were at risk of relapse following autologous stem cell transplant (ASCT).
Brentuximab vedotin conferred a 75% improvement in PFS over placebo.
However, there was no significant difference in overall survival between the 2 treatment arms.
These results were recently announced by Seattle Genetics Inc. and Takeda Pharmaceutical Company Limited, the companies developing brentuximab vedotin (Adcetris).
The companies said more complete results from AETHERA will be presented at the 2014 ASH Annual Meeting in December.
AETHERA is a randomized, double-blind, placebo-controlled study designed to evaluate the potential of brentuximab vedotin to extend PFS post-ASCT in patients with HL who have at least one risk factor for progression. In addition to the primary endpoint of PFS, secondary endpoints included overall survival, safety, and tolerability.
Patients were eligible if they had risk factors for residual HL, defined as a history of refractory HL, those who relapse or progress within a year of receiving frontline chemotherapy, and/or those who have disease outside of the lymph nodes at the time of pre-ASCT relapse.
The study included 329 patients who received brentuximab vedotin or placebo every 3 weeks for up to a year.
The researchers assessed PFS a minimum of 2 years after the initiation of treatment for all patients. There was a significant improvement in PFS with brentuximab vedotin compared to placebo (hazard ratio=0.57; P=0.001).
However, a prespecified interim analysis of overall survival showed no significant difference between the treatment arms.
Patients in both arms who experienced progression received a variety of subsequent therapies. Most patients on the placebo arm received brentuximab vedotin after progression.
A further analysis of overall survival is planned in 2016. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.
“We anticipate reporting more complete AETHERA data at the ASH Annual Meeting in December and intend to submit a supplemental Biologics License Application to the FDA in 2015 for approval in this setting,” said Clay B. Siegall, PhD, President and Chief Executive Officer of Seattle Genetics.
The FDA has already granted brentuximab vedotin accelerated approval to treat HL patients after ASCT failure or after the failure of at least 2 prior multiagent chemotherapy regimens in patients who are not ASCT candidates. The FDA also granted the drug accelerated approval to treat systemic anaplastic large cell lymphoma after the failure of at least 1 prior multiagent chemotherapy regimen.
The European Commission granted brentuximab vedotin conditional marketing authorization for the same indications. In both cases, the drug can gain full, traditional approval once studies have shown it confers a clinical benefit.
Brentuximab vedotin has a boxed warning detailing the risk of progressive multifocal leukoencephalopathy associated with use of the drug. The drug has also been shown to pose a risk of pulmonary toxicity when combined with bleomycin.
Maintenance may be unnecessary in FL
Credit: Bill Branson
New research suggests maintenance therapy may not be necessary for patients with follicular lymphoma (FL) who have a low tumor burden.
Investigators compared rituximab re-treatment with rituximab maintenance in nearly 300 FL patients, and results showed no significant difference between the treatment groups in the time to disease recurrence.
The researchers also noted that the re-treatment strategy was more cost-effective.
“For those 2 reasons, we recommend a retreatment strategy over a maintenance strategy in this patient population,” said Brad S. Kahl, MD, of the University of Wisconsin in Madison.
Dr Kahl and his colleagues described this research—the RESORT trial—in the Journal of Clinical Oncology. Early results from this trial were previously presented at the 2011 ASH Annual Meeting.
The team evaluated 289 patients with previously untreated, low-tumor-burden FL. All patients responded to initial treatment with rituximab (4 doses).
Patients were then randomized to receive maintenance therapy—a single dose of rituximab every 3 months until treatment failure—or rituximab re-treatment upon disease recurrence. Patients receiving re-treatment could receive rituximab every time they experienced progression, until treatment failure.
The median number of rituximab doses was 4 in the re-treatment arm and 18 in the maintenance arm. Three-year freedom from cytotoxic therapy was 84% in the re-treatment arm and 95% in the maintenance arm (P=0.03).
There was no significant difference between the arms in the time to disease recurrence. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years in the re-treatment arm and 4.3 years in the maintenance arm (P=0.54).
The researchers found no difference in health-related quality of life or anxiety between the treatment arms.
They also said grade 3 to 5 adverse events were infrequent in both arms. One patient developed progressive multifocal leukoencephalopathy after the 15th maintenance dose of rituximab and died.
Second malignancies were reported in 16 patients receiving re-treatment and 14 patients on maintenance therapy, but there were no obvious trends toward specific cancers.
“The study shows that a rituximab re-treatment strategy provides comparable disease control to a maintenance strategy in low-tumor-burden follicular lymphoma,” Dr Kahl said. “In addition, a re-treatment strategy is more cost-effective, as it requires about a quarter as much drug utilization.”
The study was accompanied by an editorial saying these results should change clinical practice.
Credit: Bill Branson
New research suggests maintenance therapy may not be necessary for patients with follicular lymphoma (FL) who have a low tumor burden.
Investigators compared rituximab re-treatment with rituximab maintenance in nearly 300 FL patients, and results showed no significant difference between the treatment groups in the time to disease recurrence.
The researchers also noted that the re-treatment strategy was more cost-effective.
“For those 2 reasons, we recommend a retreatment strategy over a maintenance strategy in this patient population,” said Brad S. Kahl, MD, of the University of Wisconsin in Madison.
Dr Kahl and his colleagues described this research—the RESORT trial—in the Journal of Clinical Oncology. Early results from this trial were previously presented at the 2011 ASH Annual Meeting.
The team evaluated 289 patients with previously untreated, low-tumor-burden FL. All patients responded to initial treatment with rituximab (4 doses).
Patients were then randomized to receive maintenance therapy—a single dose of rituximab every 3 months until treatment failure—or rituximab re-treatment upon disease recurrence. Patients receiving re-treatment could receive rituximab every time they experienced progression, until treatment failure.
The median number of rituximab doses was 4 in the re-treatment arm and 18 in the maintenance arm. Three-year freedom from cytotoxic therapy was 84% in the re-treatment arm and 95% in the maintenance arm (P=0.03).
There was no significant difference between the arms in the time to disease recurrence. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years in the re-treatment arm and 4.3 years in the maintenance arm (P=0.54).
The researchers found no difference in health-related quality of life or anxiety between the treatment arms.
They also said grade 3 to 5 adverse events were infrequent in both arms. One patient developed progressive multifocal leukoencephalopathy after the 15th maintenance dose of rituximab and died.
Second malignancies were reported in 16 patients receiving re-treatment and 14 patients on maintenance therapy, but there were no obvious trends toward specific cancers.
“The study shows that a rituximab re-treatment strategy provides comparable disease control to a maintenance strategy in low-tumor-burden follicular lymphoma,” Dr Kahl said. “In addition, a re-treatment strategy is more cost-effective, as it requires about a quarter as much drug utilization.”
The study was accompanied by an editorial saying these results should change clinical practice.
Credit: Bill Branson
New research suggests maintenance therapy may not be necessary for patients with follicular lymphoma (FL) who have a low tumor burden.
Investigators compared rituximab re-treatment with rituximab maintenance in nearly 300 FL patients, and results showed no significant difference between the treatment groups in the time to disease recurrence.
The researchers also noted that the re-treatment strategy was more cost-effective.
“For those 2 reasons, we recommend a retreatment strategy over a maintenance strategy in this patient population,” said Brad S. Kahl, MD, of the University of Wisconsin in Madison.
Dr Kahl and his colleagues described this research—the RESORT trial—in the Journal of Clinical Oncology. Early results from this trial were previously presented at the 2011 ASH Annual Meeting.
The team evaluated 289 patients with previously untreated, low-tumor-burden FL. All patients responded to initial treatment with rituximab (4 doses).
Patients were then randomized to receive maintenance therapy—a single dose of rituximab every 3 months until treatment failure—or rituximab re-treatment upon disease recurrence. Patients receiving re-treatment could receive rituximab every time they experienced progression, until treatment failure.
The median number of rituximab doses was 4 in the re-treatment arm and 18 in the maintenance arm. Three-year freedom from cytotoxic therapy was 84% in the re-treatment arm and 95% in the maintenance arm (P=0.03).
There was no significant difference between the arms in the time to disease recurrence. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years in the re-treatment arm and 4.3 years in the maintenance arm (P=0.54).
The researchers found no difference in health-related quality of life or anxiety between the treatment arms.
They also said grade 3 to 5 adverse events were infrequent in both arms. One patient developed progressive multifocal leukoencephalopathy after the 15th maintenance dose of rituximab and died.
Second malignancies were reported in 16 patients receiving re-treatment and 14 patients on maintenance therapy, but there were no obvious trends toward specific cancers.
“The study shows that a rituximab re-treatment strategy provides comparable disease control to a maintenance strategy in low-tumor-burden follicular lymphoma,” Dr Kahl said. “In addition, a re-treatment strategy is more cost-effective, as it requires about a quarter as much drug utilization.”
The study was accompanied by an editorial saying these results should change clinical practice.
Combo shows potential as frontline therapy in PTCL
Credit: NIH
MADRID—Follow-up data from a phase 1 trial suggest brentuximab vedotin plus chemotherapy may be a feasible frontline option for patients with peripheral T-cell lymphoma (PTCL).
At the ESMO 2014 Congress, investigators presented a 2-year durability analysis from a trial of brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV+CHP) in patients newly diagnosed with PTCL.
The estimated 2-year overall survival rate was 80% in these patients. And the median progression-free survival was not reached.
Michelle Fanale, MD, of The University of Texas MD Anderson Cancer Center in Houston, and her colleagues reported these results as abstract 944O.
The research was sponsored by Seattle Genetics Inc. and Takeda Pharmaceuticals International, the companies co-developing brentuximab vedotin (Adcetris).
In this trial, patients received 1 of 2 treatment regimens. The first was sequential treatment (once every 3 weeks) with brentuximab vedotin at 1.8 mg/kg for 2 cycles, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for 6 cycles.
The second was combination BV+CHP every 3 weeks for 6 cycles. Patients who achieved at least a partial response after 6 cycles of treatment were eligible to receive continued single-agent brentuximab vedotin for up to 10 additional 3-week cycles.
Earlier results with both treatment regimens were published in the Journal of Clinical Oncology. At ESMO, Dr Fanale presented 2-year results among the 26 patients who received BV+CHP.
The median patient age was 56 years. Nineteen patients had systemic anaplastic large-cell lymphoma (sALCL), including 16 patients (62%) with ALK-negative disease.
Two patients had PTCL not otherwise specified, 2 had angioimmunoblastic T-cell lymphoma, 2 had adult T-cell leukemia/lymphoma, and 1 had enteropathy-associated T-cell lymphoma. The majority of patients had advanced-stage disease and/or were considered high risk.
All 26 patients had an objective response to BV+CHP, including 23 patients (88%) with a complete response. All 23 patients who achieved a complete remission demonstrated normalized glucose uptake by PET.
The median observation time was 27.1 months from the first dose of therapy. The estimated 2-year progression-free survival rate was 54%, with no patients receiving a consolidative stem cell transplant. And the estimated 2-year overall survival rate was 80%.
The most common treatment-emergent adverse events of any grade occurring in more than 40% of patients were peripheral sensory neuropathy, nausea, fatigue, hair loss, diarrhea, and shortness of breath.
Based on the results of this study, Seattle Genetics and Takeda initiated a global phase 3 study called ECHELON-2. This randomized, double-blind, placebo-controlled, multicenter trial was designed to investigate BV+CHP vs CHOP as frontline therapy in patients with CD30-positive PTCL.
The study is currently enrolling patients. It is expected to enroll 300 patients, who will be randomized to receive either treatment every 3 weeks for 6 to 8 cycles.
Credit: NIH
MADRID—Follow-up data from a phase 1 trial suggest brentuximab vedotin plus chemotherapy may be a feasible frontline option for patients with peripheral T-cell lymphoma (PTCL).
At the ESMO 2014 Congress, investigators presented a 2-year durability analysis from a trial of brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV+CHP) in patients newly diagnosed with PTCL.
The estimated 2-year overall survival rate was 80% in these patients. And the median progression-free survival was not reached.
Michelle Fanale, MD, of The University of Texas MD Anderson Cancer Center in Houston, and her colleagues reported these results as abstract 944O.
The research was sponsored by Seattle Genetics Inc. and Takeda Pharmaceuticals International, the companies co-developing brentuximab vedotin (Adcetris).
In this trial, patients received 1 of 2 treatment regimens. The first was sequential treatment (once every 3 weeks) with brentuximab vedotin at 1.8 mg/kg for 2 cycles, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for 6 cycles.
The second was combination BV+CHP every 3 weeks for 6 cycles. Patients who achieved at least a partial response after 6 cycles of treatment were eligible to receive continued single-agent brentuximab vedotin for up to 10 additional 3-week cycles.
Earlier results with both treatment regimens were published in the Journal of Clinical Oncology. At ESMO, Dr Fanale presented 2-year results among the 26 patients who received BV+CHP.
The median patient age was 56 years. Nineteen patients had systemic anaplastic large-cell lymphoma (sALCL), including 16 patients (62%) with ALK-negative disease.
Two patients had PTCL not otherwise specified, 2 had angioimmunoblastic T-cell lymphoma, 2 had adult T-cell leukemia/lymphoma, and 1 had enteropathy-associated T-cell lymphoma. The majority of patients had advanced-stage disease and/or were considered high risk.
All 26 patients had an objective response to BV+CHP, including 23 patients (88%) with a complete response. All 23 patients who achieved a complete remission demonstrated normalized glucose uptake by PET.
The median observation time was 27.1 months from the first dose of therapy. The estimated 2-year progression-free survival rate was 54%, with no patients receiving a consolidative stem cell transplant. And the estimated 2-year overall survival rate was 80%.
The most common treatment-emergent adverse events of any grade occurring in more than 40% of patients were peripheral sensory neuropathy, nausea, fatigue, hair loss, diarrhea, and shortness of breath.
Based on the results of this study, Seattle Genetics and Takeda initiated a global phase 3 study called ECHELON-2. This randomized, double-blind, placebo-controlled, multicenter trial was designed to investigate BV+CHP vs CHOP as frontline therapy in patients with CD30-positive PTCL.
The study is currently enrolling patients. It is expected to enroll 300 patients, who will be randomized to receive either treatment every 3 weeks for 6 to 8 cycles.
Credit: NIH
MADRID—Follow-up data from a phase 1 trial suggest brentuximab vedotin plus chemotherapy may be a feasible frontline option for patients with peripheral T-cell lymphoma (PTCL).
At the ESMO 2014 Congress, investigators presented a 2-year durability analysis from a trial of brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (BV+CHP) in patients newly diagnosed with PTCL.
The estimated 2-year overall survival rate was 80% in these patients. And the median progression-free survival was not reached.
Michelle Fanale, MD, of The University of Texas MD Anderson Cancer Center in Houston, and her colleagues reported these results as abstract 944O.
The research was sponsored by Seattle Genetics Inc. and Takeda Pharmaceuticals International, the companies co-developing brentuximab vedotin (Adcetris).
In this trial, patients received 1 of 2 treatment regimens. The first was sequential treatment (once every 3 weeks) with brentuximab vedotin at 1.8 mg/kg for 2 cycles, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for 6 cycles.
The second was combination BV+CHP every 3 weeks for 6 cycles. Patients who achieved at least a partial response after 6 cycles of treatment were eligible to receive continued single-agent brentuximab vedotin for up to 10 additional 3-week cycles.
Earlier results with both treatment regimens were published in the Journal of Clinical Oncology. At ESMO, Dr Fanale presented 2-year results among the 26 patients who received BV+CHP.
The median patient age was 56 years. Nineteen patients had systemic anaplastic large-cell lymphoma (sALCL), including 16 patients (62%) with ALK-negative disease.
Two patients had PTCL not otherwise specified, 2 had angioimmunoblastic T-cell lymphoma, 2 had adult T-cell leukemia/lymphoma, and 1 had enteropathy-associated T-cell lymphoma. The majority of patients had advanced-stage disease and/or were considered high risk.
All 26 patients had an objective response to BV+CHP, including 23 patients (88%) with a complete response. All 23 patients who achieved a complete remission demonstrated normalized glucose uptake by PET.
The median observation time was 27.1 months from the first dose of therapy. The estimated 2-year progression-free survival rate was 54%, with no patients receiving a consolidative stem cell transplant. And the estimated 2-year overall survival rate was 80%.
The most common treatment-emergent adverse events of any grade occurring in more than 40% of patients were peripheral sensory neuropathy, nausea, fatigue, hair loss, diarrhea, and shortness of breath.
Based on the results of this study, Seattle Genetics and Takeda initiated a global phase 3 study called ECHELON-2. This randomized, double-blind, placebo-controlled, multicenter trial was designed to investigate BV+CHP vs CHOP as frontline therapy in patients with CD30-positive PTCL.
The study is currently enrolling patients. It is expected to enroll 300 patients, who will be randomized to receive either treatment every 3 weeks for 6 to 8 cycles.
Drug can prevent chemo-induced nausea, vomiting
Credit: Rhoda Baer
MADRID—A small molecule called rolapitant can prevent nausea and vomiting in patients receiving cisplatin-based chemotherapy, results of a phase 3 trial suggest.
When given prior to chemotherapy, rolapitant induced a complete response in about 70% of patients.
These patients had no emesis after chemotherapy and did not require any rescue medication.
“This agent makes a significant difference in the way people tolerate their chemotherapy,” said Martin Chasen, MD, of Ottawa Hospital Cancer Centre in Canada.
“Patients experienced no loss in quality of life, and, in fact, many saw meaningful improvements. One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf one week after receiving chemotherapy. This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin.”
Dr Chasen and his colleagues reported these results at the ESMO 2014 Congress (abstract LBA47_PR).
The team had set out to evaluate rolapitant, a novel antagonist of the NK-1 receptor, for the prevention of severe nausea and vomiting often experienced by patients receiving cisplatin-based chemotherapy, which may cause dose reductions and treatment discontinuation.
The trial included 532 patients who were randomized 1:1 to receive rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to chemotherapy.
The primary endpoint was complete response (defined as the patient having no emesis and not requiring any rescue medication) in the delayed phase (>24-120 hours) post-chemotherapy. Key secondary endpoints included complete response during the acute phase (0-24 hours) and overall (0-120 hours).
The trial met its primary endpoint, with 72.7% of patients receiving rolapitant achieving a complete response in the delayed phase, compared to 58.4% of those receiving placebo (P<0.001).
Rolapitant also improved the complete response rate compared to placebo in the acute phase—83.7% and 73.7%, respectively (P=0.005).
Overall, the complete response rates were 70.1% and 56.5%, respectively (P=0.001).
Patients receiving rolapitant tended to report that chemotherapy had less of an impact on their daily quality of life, although the difference between the treatment arms was not significant—72.8% vs 67.8% (P=0.231).
“Rolapitant demonstrated a significant effect in both the acute and delayed phases,” Dr Chasen noted. “Our primary endpoint was achieved in the delayed phase—an incredible result.”
“We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting. Rolapitant is an exceptionally long-term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting.”
Dr Chasen added that rolapitant may prove effective in patients receiving less emetogenic cancer treatments as well.
Credit: Rhoda Baer
MADRID—A small molecule called rolapitant can prevent nausea and vomiting in patients receiving cisplatin-based chemotherapy, results of a phase 3 trial suggest.
When given prior to chemotherapy, rolapitant induced a complete response in about 70% of patients.
These patients had no emesis after chemotherapy and did not require any rescue medication.
“This agent makes a significant difference in the way people tolerate their chemotherapy,” said Martin Chasen, MD, of Ottawa Hospital Cancer Centre in Canada.
“Patients experienced no loss in quality of life, and, in fact, many saw meaningful improvements. One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf one week after receiving chemotherapy. This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin.”
Dr Chasen and his colleagues reported these results at the ESMO 2014 Congress (abstract LBA47_PR).
The team had set out to evaluate rolapitant, a novel antagonist of the NK-1 receptor, for the prevention of severe nausea and vomiting often experienced by patients receiving cisplatin-based chemotherapy, which may cause dose reductions and treatment discontinuation.
The trial included 532 patients who were randomized 1:1 to receive rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to chemotherapy.
The primary endpoint was complete response (defined as the patient having no emesis and not requiring any rescue medication) in the delayed phase (>24-120 hours) post-chemotherapy. Key secondary endpoints included complete response during the acute phase (0-24 hours) and overall (0-120 hours).
The trial met its primary endpoint, with 72.7% of patients receiving rolapitant achieving a complete response in the delayed phase, compared to 58.4% of those receiving placebo (P<0.001).
Rolapitant also improved the complete response rate compared to placebo in the acute phase—83.7% and 73.7%, respectively (P=0.005).
Overall, the complete response rates were 70.1% and 56.5%, respectively (P=0.001).
Patients receiving rolapitant tended to report that chemotherapy had less of an impact on their daily quality of life, although the difference between the treatment arms was not significant—72.8% vs 67.8% (P=0.231).
“Rolapitant demonstrated a significant effect in both the acute and delayed phases,” Dr Chasen noted. “Our primary endpoint was achieved in the delayed phase—an incredible result.”
“We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting. Rolapitant is an exceptionally long-term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting.”
Dr Chasen added that rolapitant may prove effective in patients receiving less emetogenic cancer treatments as well.
Credit: Rhoda Baer
MADRID—A small molecule called rolapitant can prevent nausea and vomiting in patients receiving cisplatin-based chemotherapy, results of a phase 3 trial suggest.
When given prior to chemotherapy, rolapitant induced a complete response in about 70% of patients.
These patients had no emesis after chemotherapy and did not require any rescue medication.
“This agent makes a significant difference in the way people tolerate their chemotherapy,” said Martin Chasen, MD, of Ottawa Hospital Cancer Centre in Canada.
“Patients experienced no loss in quality of life, and, in fact, many saw meaningful improvements. One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf one week after receiving chemotherapy. This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin.”
Dr Chasen and his colleagues reported these results at the ESMO 2014 Congress (abstract LBA47_PR).
The team had set out to evaluate rolapitant, a novel antagonist of the NK-1 receptor, for the prevention of severe nausea and vomiting often experienced by patients receiving cisplatin-based chemotherapy, which may cause dose reductions and treatment discontinuation.
The trial included 532 patients who were randomized 1:1 to receive rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to chemotherapy.
The primary endpoint was complete response (defined as the patient having no emesis and not requiring any rescue medication) in the delayed phase (>24-120 hours) post-chemotherapy. Key secondary endpoints included complete response during the acute phase (0-24 hours) and overall (0-120 hours).
The trial met its primary endpoint, with 72.7% of patients receiving rolapitant achieving a complete response in the delayed phase, compared to 58.4% of those receiving placebo (P<0.001).
Rolapitant also improved the complete response rate compared to placebo in the acute phase—83.7% and 73.7%, respectively (P=0.005).
Overall, the complete response rates were 70.1% and 56.5%, respectively (P=0.001).
Patients receiving rolapitant tended to report that chemotherapy had less of an impact on their daily quality of life, although the difference between the treatment arms was not significant—72.8% vs 67.8% (P=0.231).
“Rolapitant demonstrated a significant effect in both the acute and delayed phases,” Dr Chasen noted. “Our primary endpoint was achieved in the delayed phase—an incredible result.”
“We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting. Rolapitant is an exceptionally long-term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting.”
Dr Chasen added that rolapitant may prove effective in patients receiving less emetogenic cancer treatments as well.
Hypercalcemia may be indicator for hematologic cancers
Credit: Graham Colm
Hypercalcemia could be an early indication of cancer, according to a study published in the British Journal of Cancer.
The connection between hypercalcemia and cancer is well known, but this study shows the condition can predate cancer diagnosis in primary care.
The association between hypercalcemia and cancers was particularly strong in men. And myeloma and other hematologic malignancies were among the most common cancers associated with hypercalcemia.
“All previous studies on hypercalcemia and cancer had been carried out with patients who had already been diagnosed with cancer; hypercalcemia was seen as a late effect of the cancer,” said study author Fergus Hamilton, of the University of Bristol in the UK.
“We wanted to look at the issue from a different perspective and find out if high calcium levels in blood could be used as an early indicator of cancer and, therefore, in the diagnosis of cancer.”
So the researchers analyzed the electronic records of 54,267 patients with elevated calcium levels and found that hypercalcemia was strongly associated with cancer, especially in males.
The positive predictive values for cancer in men were 11.5% for calcium levels between 2.60 and 2.79 mmol l-1, 27.9% for 2.8-2.99 mmol l-1, and 50% for >3.0 mmol l-1. In women, the corresponding values were 4.1%, 8.7%, and 16.7%, respectively.
In men, the most common cancers associated with hypercalcemia were lung (34%), prostate (21%), colorectal (8%), myeloma (8%), and other hematologic cancers (8%). There were 12 other cancer types recorded as well (19%).
In women, the most common cancers were myeloma (24%), breast (18%), other hematologic cancers (10%), lung (8%), and metastatic cancer with unknown primary (8%). There were 16 other cancers recorded among women (32%).
The researchers found no difference in calcium levels among the different cancers.
“We were surprised by the gender difference,” Dr Hamilton said. “There are a number of possible explanations for this, but we think it might be because women are much more likely to have hyperparathyroidism, another cause of hypercalcemia. Men rarely get this condition, so their hypercalcemia is more likely to be due to cancer.”
Credit: Graham Colm
Hypercalcemia could be an early indication of cancer, according to a study published in the British Journal of Cancer.
The connection between hypercalcemia and cancer is well known, but this study shows the condition can predate cancer diagnosis in primary care.
The association between hypercalcemia and cancers was particularly strong in men. And myeloma and other hematologic malignancies were among the most common cancers associated with hypercalcemia.
“All previous studies on hypercalcemia and cancer had been carried out with patients who had already been diagnosed with cancer; hypercalcemia was seen as a late effect of the cancer,” said study author Fergus Hamilton, of the University of Bristol in the UK.
“We wanted to look at the issue from a different perspective and find out if high calcium levels in blood could be used as an early indicator of cancer and, therefore, in the diagnosis of cancer.”
So the researchers analyzed the electronic records of 54,267 patients with elevated calcium levels and found that hypercalcemia was strongly associated with cancer, especially in males.
The positive predictive values for cancer in men were 11.5% for calcium levels between 2.60 and 2.79 mmol l-1, 27.9% for 2.8-2.99 mmol l-1, and 50% for >3.0 mmol l-1. In women, the corresponding values were 4.1%, 8.7%, and 16.7%, respectively.
In men, the most common cancers associated with hypercalcemia were lung (34%), prostate (21%), colorectal (8%), myeloma (8%), and other hematologic cancers (8%). There were 12 other cancer types recorded as well (19%).
In women, the most common cancers were myeloma (24%), breast (18%), other hematologic cancers (10%), lung (8%), and metastatic cancer with unknown primary (8%). There were 16 other cancers recorded among women (32%).
The researchers found no difference in calcium levels among the different cancers.
“We were surprised by the gender difference,” Dr Hamilton said. “There are a number of possible explanations for this, but we think it might be because women are much more likely to have hyperparathyroidism, another cause of hypercalcemia. Men rarely get this condition, so their hypercalcemia is more likely to be due to cancer.”
Credit: Graham Colm
Hypercalcemia could be an early indication of cancer, according to a study published in the British Journal of Cancer.
The connection between hypercalcemia and cancer is well known, but this study shows the condition can predate cancer diagnosis in primary care.
The association between hypercalcemia and cancers was particularly strong in men. And myeloma and other hematologic malignancies were among the most common cancers associated with hypercalcemia.
“All previous studies on hypercalcemia and cancer had been carried out with patients who had already been diagnosed with cancer; hypercalcemia was seen as a late effect of the cancer,” said study author Fergus Hamilton, of the University of Bristol in the UK.
“We wanted to look at the issue from a different perspective and find out if high calcium levels in blood could be used as an early indicator of cancer and, therefore, in the diagnosis of cancer.”
So the researchers analyzed the electronic records of 54,267 patients with elevated calcium levels and found that hypercalcemia was strongly associated with cancer, especially in males.
The positive predictive values for cancer in men were 11.5% for calcium levels between 2.60 and 2.79 mmol l-1, 27.9% for 2.8-2.99 mmol l-1, and 50% for >3.0 mmol l-1. In women, the corresponding values were 4.1%, 8.7%, and 16.7%, respectively.
In men, the most common cancers associated with hypercalcemia were lung (34%), prostate (21%), colorectal (8%), myeloma (8%), and other hematologic cancers (8%). There were 12 other cancer types recorded as well (19%).
In women, the most common cancers were myeloma (24%), breast (18%), other hematologic cancers (10%), lung (8%), and metastatic cancer with unknown primary (8%). There were 16 other cancers recorded among women (32%).
The researchers found no difference in calcium levels among the different cancers.
“We were surprised by the gender difference,” Dr Hamilton said. “There are a number of possible explanations for this, but we think it might be because women are much more likely to have hyperparathyroidism, another cause of hypercalcemia. Men rarely get this condition, so their hypercalcemia is more likely to be due to cancer.”
Preventing cancer-related infection
Credit: CDC/Kimberly Smith
and Christine Ford
NEW YORK—Hand washing is still the single most effective method to prevent the transmission of infection, but additional measures can reduce the risk of cancer-related infections, according to a speaker at the NCCN 9th Annual Congress: Hematologic Malignancies.
In her presentation, Laura Zitella, RN, of the Stanford Cancer Institute in California, discussed current recommendations for pharmacologic and non-pharmacologic infection prophylaxis.
She noted that NCCN Guidelines on the Prevention and Treatment of Cancer-Related Infections state that the highest risk of infection is in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), acute leukemia patients undergoing induction or consolidation therapy, patients receiving alemtuzumab therapy, patients with graft-vs-host disease (GVHD) treated with high-dose steroids, and patients with neutropenia anticipated to last greater than 10 days.
Antibiotic prophylaxis
Prior to 2005, Zitella said, no survival benefit was observed for antibiotic prophylaxis. All of this changed with the results of a meta-analysis. The analysis included 95 randomized, controlled trials and 9283 patients, the majority having acute leukemia or undergoing HSCT.
For the first time, antibiotic prophylaxis was shown to confer a survival benefit. In neutropenic patients, prophylaxis reduced overall mortality by 33% and infection-related mortality by 42%, compared with placebo or no treatment.
Prophylaxis is not recommended for low-risk neutropenic patients, Zitella said, because it is not proven to decrease morality.
And the drugs of choice are levofloxacin (500-750 mg PO daily) or ciprofloxacin (500-750 mg PO twice daily).
Colony-stimulating factors
Consensus guidelines for the use of colony-stimulating factors (CSFs) are a compilation of ASCO, EORTC, ESMO, and NCCN guidelines.
CSFs may be used prophylactically to prevent chemotherapy-induced neutropenia, febrile neutropenia, and infection. They reduce the duration of hospitalization, the duration of parenteral antibiotics, and have shown a survival benefit.
CSFs are recommended if the risk of febrile neutropenia is 20% or greater. CSFs are not routinely recommended for patients undergoing radiation treatment, acute myeloid leukemia induction, or patients with Hodgkin lymphoma.
Antifungal prophylaxis
Zitella noted that fluconazole is the best-studied antifungal prophylaxis and is recommended as the primary prophylaxis for HSCT patients.
In double-blind, placebo-controlled trials, fluconazole reduced mucosal candidiasis and invasive Candida infections in patients undergoing HSCT. And it improved survival at day 110 after transplant.
Posaconazole prophylaxis has proven effective in patients with acute myeloid leukemia or myelodysplastic syndromes undergoing intensive chemotherapy. The drug reduced invasive fungal infections, including aspergillosis, and improved survival.
For patients with GVHD on immunosuppressive therapy, posaconazole and fluconazole prophylaxis were equivalent in preventing invasive fungal infections. However, posaconazole reduced the incidence of invasive aspergillosis and fungal-related mortality.
The NCCN guidelines, Zitella said, spell out which antifungal agents should be used for each disease or therapeutic intervention.
Antiviral prophylaxis
HSV and VZV
Patients requiring antiviral prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) should be seropositive and have acute leukemia, GVHD treated with steroids, prior HSV reactivation under treatment, or have undergone HSCT.
Zitella pointed out that patients treated with proteasome inhibitors, such as bortezomib, alemtuzumab, or purine analaogs, such as fludarabine, are more at risk and should also receive antiviral prophylaxis.
Recommended drugs include valacyclovir, acyclovir, or famciclovir.
CMV
Cytomegalovirus-positive (CMV+) patients at high risk include those who have received an allogeneic HSCT or treatment with alemtuzumab.
Zitella explained that for these patients, prophylaxis is uncommon, and a pre-emptive strategy should be used, including testing 3 to 6 months after transplant or in the setting of GVHD and 2 months after alemtuzumab therapy.
CMV viremia should be treated with valganciclovir, ganciclovir, foscarnet, or cidofovir.
HBV
Zitella noted that 30% of the world population has been infected with hepatitis B virus (HBV), and reactivation during cancer treatment can lead to fulminant hepatitis and death.
NCCN recommends that patients undergoing immunosuppressive therapy, allogeneic HSCT candidates, patients receiving anti-CD20 monoclonal antibodies, those treated with alemtuzumab, and patients receiving systemic therapy who have an obvious risk factor for HBV infection should be tested.
Entecavir, tenofovir, adefovir, telbivudine, or lamivudine may be used to prevent HBV reactivation.
Pneumocystis pneumonia prophylaxis
Patients undergoing allogeneic HSCT, patients with acute lymphoblastic leukemia, those treated with alemtuzumab, and those with a CD4 count below 200 cells/mcL should receive pneumocystis pneumonia prophylaxis.
Trimethorpim/sulfamethoxazole is the drug of choice. Atovaquone, dapsone, and inhaled or IV pentamidine are alternatives.
Vaccines
Zitella pointed out that recommended vaccines include influenza, pneumococcal, and tetanus, diphtheria, and acellular pertussis.
She cautioned that live attenuated vaccines should not be given to cancer patients. Other vaccines to avoid include smallpox; measles, mumps, and rubella; varicella zoster; rotavirus; yellow fever; oral typhoid; BCG; and oral polio vaccine.
Neutropenic precautions
Low microbial diets are a hot topic among patients undergoing cancer treatment, Zitella said. Fresh fruits and vegetables used to be restricted, but no studies show that dietary restrictions decrease the risk of infection.
Zitella stressed, however, that standard food safety recommendations of the USDA/FDA should be followed.
She also noted that HEPA filtration is protective against molds in high-risk patients, antiseptic bathing has contradictory evidence, the benefit of laminar airflow is unclear, and protective isolation has not been proven to reduce the risk of infection.
Credit: CDC/Kimberly Smith
and Christine Ford
NEW YORK—Hand washing is still the single most effective method to prevent the transmission of infection, but additional measures can reduce the risk of cancer-related infections, according to a speaker at the NCCN 9th Annual Congress: Hematologic Malignancies.
In her presentation, Laura Zitella, RN, of the Stanford Cancer Institute in California, discussed current recommendations for pharmacologic and non-pharmacologic infection prophylaxis.
She noted that NCCN Guidelines on the Prevention and Treatment of Cancer-Related Infections state that the highest risk of infection is in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), acute leukemia patients undergoing induction or consolidation therapy, patients receiving alemtuzumab therapy, patients with graft-vs-host disease (GVHD) treated with high-dose steroids, and patients with neutropenia anticipated to last greater than 10 days.
Antibiotic prophylaxis
Prior to 2005, Zitella said, no survival benefit was observed for antibiotic prophylaxis. All of this changed with the results of a meta-analysis. The analysis included 95 randomized, controlled trials and 9283 patients, the majority having acute leukemia or undergoing HSCT.
For the first time, antibiotic prophylaxis was shown to confer a survival benefit. In neutropenic patients, prophylaxis reduced overall mortality by 33% and infection-related mortality by 42%, compared with placebo or no treatment.
Prophylaxis is not recommended for low-risk neutropenic patients, Zitella said, because it is not proven to decrease morality.
And the drugs of choice are levofloxacin (500-750 mg PO daily) or ciprofloxacin (500-750 mg PO twice daily).
Colony-stimulating factors
Consensus guidelines for the use of colony-stimulating factors (CSFs) are a compilation of ASCO, EORTC, ESMO, and NCCN guidelines.
CSFs may be used prophylactically to prevent chemotherapy-induced neutropenia, febrile neutropenia, and infection. They reduce the duration of hospitalization, the duration of parenteral antibiotics, and have shown a survival benefit.
CSFs are recommended if the risk of febrile neutropenia is 20% or greater. CSFs are not routinely recommended for patients undergoing radiation treatment, acute myeloid leukemia induction, or patients with Hodgkin lymphoma.
Antifungal prophylaxis
Zitella noted that fluconazole is the best-studied antifungal prophylaxis and is recommended as the primary prophylaxis for HSCT patients.
In double-blind, placebo-controlled trials, fluconazole reduced mucosal candidiasis and invasive Candida infections in patients undergoing HSCT. And it improved survival at day 110 after transplant.
Posaconazole prophylaxis has proven effective in patients with acute myeloid leukemia or myelodysplastic syndromes undergoing intensive chemotherapy. The drug reduced invasive fungal infections, including aspergillosis, and improved survival.
For patients with GVHD on immunosuppressive therapy, posaconazole and fluconazole prophylaxis were equivalent in preventing invasive fungal infections. However, posaconazole reduced the incidence of invasive aspergillosis and fungal-related mortality.
The NCCN guidelines, Zitella said, spell out which antifungal agents should be used for each disease or therapeutic intervention.
Antiviral prophylaxis
HSV and VZV
Patients requiring antiviral prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) should be seropositive and have acute leukemia, GVHD treated with steroids, prior HSV reactivation under treatment, or have undergone HSCT.
Zitella pointed out that patients treated with proteasome inhibitors, such as bortezomib, alemtuzumab, or purine analaogs, such as fludarabine, are more at risk and should also receive antiviral prophylaxis.
Recommended drugs include valacyclovir, acyclovir, or famciclovir.
CMV
Cytomegalovirus-positive (CMV+) patients at high risk include those who have received an allogeneic HSCT or treatment with alemtuzumab.
Zitella explained that for these patients, prophylaxis is uncommon, and a pre-emptive strategy should be used, including testing 3 to 6 months after transplant or in the setting of GVHD and 2 months after alemtuzumab therapy.
CMV viremia should be treated with valganciclovir, ganciclovir, foscarnet, or cidofovir.
HBV
Zitella noted that 30% of the world population has been infected with hepatitis B virus (HBV), and reactivation during cancer treatment can lead to fulminant hepatitis and death.
NCCN recommends that patients undergoing immunosuppressive therapy, allogeneic HSCT candidates, patients receiving anti-CD20 monoclonal antibodies, those treated with alemtuzumab, and patients receiving systemic therapy who have an obvious risk factor for HBV infection should be tested.
Entecavir, tenofovir, adefovir, telbivudine, or lamivudine may be used to prevent HBV reactivation.
Pneumocystis pneumonia prophylaxis
Patients undergoing allogeneic HSCT, patients with acute lymphoblastic leukemia, those treated with alemtuzumab, and those with a CD4 count below 200 cells/mcL should receive pneumocystis pneumonia prophylaxis.
Trimethorpim/sulfamethoxazole is the drug of choice. Atovaquone, dapsone, and inhaled or IV pentamidine are alternatives.
Vaccines
Zitella pointed out that recommended vaccines include influenza, pneumococcal, and tetanus, diphtheria, and acellular pertussis.
She cautioned that live attenuated vaccines should not be given to cancer patients. Other vaccines to avoid include smallpox; measles, mumps, and rubella; varicella zoster; rotavirus; yellow fever; oral typhoid; BCG; and oral polio vaccine.
Neutropenic precautions
Low microbial diets are a hot topic among patients undergoing cancer treatment, Zitella said. Fresh fruits and vegetables used to be restricted, but no studies show that dietary restrictions decrease the risk of infection.
Zitella stressed, however, that standard food safety recommendations of the USDA/FDA should be followed.
She also noted that HEPA filtration is protective against molds in high-risk patients, antiseptic bathing has contradictory evidence, the benefit of laminar airflow is unclear, and protective isolation has not been proven to reduce the risk of infection.
Credit: CDC/Kimberly Smith
and Christine Ford
NEW YORK—Hand washing is still the single most effective method to prevent the transmission of infection, but additional measures can reduce the risk of cancer-related infections, according to a speaker at the NCCN 9th Annual Congress: Hematologic Malignancies.
In her presentation, Laura Zitella, RN, of the Stanford Cancer Institute in California, discussed current recommendations for pharmacologic and non-pharmacologic infection prophylaxis.
She noted that NCCN Guidelines on the Prevention and Treatment of Cancer-Related Infections state that the highest risk of infection is in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), acute leukemia patients undergoing induction or consolidation therapy, patients receiving alemtuzumab therapy, patients with graft-vs-host disease (GVHD) treated with high-dose steroids, and patients with neutropenia anticipated to last greater than 10 days.
Antibiotic prophylaxis
Prior to 2005, Zitella said, no survival benefit was observed for antibiotic prophylaxis. All of this changed with the results of a meta-analysis. The analysis included 95 randomized, controlled trials and 9283 patients, the majority having acute leukemia or undergoing HSCT.
For the first time, antibiotic prophylaxis was shown to confer a survival benefit. In neutropenic patients, prophylaxis reduced overall mortality by 33% and infection-related mortality by 42%, compared with placebo or no treatment.
Prophylaxis is not recommended for low-risk neutropenic patients, Zitella said, because it is not proven to decrease morality.
And the drugs of choice are levofloxacin (500-750 mg PO daily) or ciprofloxacin (500-750 mg PO twice daily).
Colony-stimulating factors
Consensus guidelines for the use of colony-stimulating factors (CSFs) are a compilation of ASCO, EORTC, ESMO, and NCCN guidelines.
CSFs may be used prophylactically to prevent chemotherapy-induced neutropenia, febrile neutropenia, and infection. They reduce the duration of hospitalization, the duration of parenteral antibiotics, and have shown a survival benefit.
CSFs are recommended if the risk of febrile neutropenia is 20% or greater. CSFs are not routinely recommended for patients undergoing radiation treatment, acute myeloid leukemia induction, or patients with Hodgkin lymphoma.
Antifungal prophylaxis
Zitella noted that fluconazole is the best-studied antifungal prophylaxis and is recommended as the primary prophylaxis for HSCT patients.
In double-blind, placebo-controlled trials, fluconazole reduced mucosal candidiasis and invasive Candida infections in patients undergoing HSCT. And it improved survival at day 110 after transplant.
Posaconazole prophylaxis has proven effective in patients with acute myeloid leukemia or myelodysplastic syndromes undergoing intensive chemotherapy. The drug reduced invasive fungal infections, including aspergillosis, and improved survival.
For patients with GVHD on immunosuppressive therapy, posaconazole and fluconazole prophylaxis were equivalent in preventing invasive fungal infections. However, posaconazole reduced the incidence of invasive aspergillosis and fungal-related mortality.
The NCCN guidelines, Zitella said, spell out which antifungal agents should be used for each disease or therapeutic intervention.
Antiviral prophylaxis
HSV and VZV
Patients requiring antiviral prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) should be seropositive and have acute leukemia, GVHD treated with steroids, prior HSV reactivation under treatment, or have undergone HSCT.
Zitella pointed out that patients treated with proteasome inhibitors, such as bortezomib, alemtuzumab, or purine analaogs, such as fludarabine, are more at risk and should also receive antiviral prophylaxis.
Recommended drugs include valacyclovir, acyclovir, or famciclovir.
CMV
Cytomegalovirus-positive (CMV+) patients at high risk include those who have received an allogeneic HSCT or treatment with alemtuzumab.
Zitella explained that for these patients, prophylaxis is uncommon, and a pre-emptive strategy should be used, including testing 3 to 6 months after transplant or in the setting of GVHD and 2 months after alemtuzumab therapy.
CMV viremia should be treated with valganciclovir, ganciclovir, foscarnet, or cidofovir.
HBV
Zitella noted that 30% of the world population has been infected with hepatitis B virus (HBV), and reactivation during cancer treatment can lead to fulminant hepatitis and death.
NCCN recommends that patients undergoing immunosuppressive therapy, allogeneic HSCT candidates, patients receiving anti-CD20 monoclonal antibodies, those treated with alemtuzumab, and patients receiving systemic therapy who have an obvious risk factor for HBV infection should be tested.
Entecavir, tenofovir, adefovir, telbivudine, or lamivudine may be used to prevent HBV reactivation.
Pneumocystis pneumonia prophylaxis
Patients undergoing allogeneic HSCT, patients with acute lymphoblastic leukemia, those treated with alemtuzumab, and those with a CD4 count below 200 cells/mcL should receive pneumocystis pneumonia prophylaxis.
Trimethorpim/sulfamethoxazole is the drug of choice. Atovaquone, dapsone, and inhaled or IV pentamidine are alternatives.
Vaccines
Zitella pointed out that recommended vaccines include influenza, pneumococcal, and tetanus, diphtheria, and acellular pertussis.
She cautioned that live attenuated vaccines should not be given to cancer patients. Other vaccines to avoid include smallpox; measles, mumps, and rubella; varicella zoster; rotavirus; yellow fever; oral typhoid; BCG; and oral polio vaccine.
Neutropenic precautions
Low microbial diets are a hot topic among patients undergoing cancer treatment, Zitella said. Fresh fruits and vegetables used to be restricted, but no studies show that dietary restrictions decrease the risk of infection.
Zitella stressed, however, that standard food safety recommendations of the USDA/FDA should be followed.
She also noted that HEPA filtration is protective against molds in high-risk patients, antiseptic bathing has contradictory evidence, the benefit of laminar airflow is unclear, and protective isolation has not been proven to reduce the risk of infection.
Drug could treat a range of blood cancers
PHILADELPHIA—A drug that targets the ribosome may be active in a broad range of hematologic malignancies, researchers say.
The drug, CX-5461, inhibits the protein RNA polymerase I (Pol I), which is consistently upregulated in hematologic and other cancers.
CX-5461 significantly prolonged survival in mouse models of refractory acute myeloid leukemia (AML) and multiple myeloma (MM). It also synergized with everolimus to extend survival in mice with B-cell lymphoma.
Furthermore, the drug did not elicit severe adverse effects.
“We were excited to find that therapeutic doses of CX-5461 had little effect on normal cells in our experiments,” said Ross D. Hannan, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Australia,
“Prior to these studies, few people would have guessed that such a therapeutic window could be obtained by targeting a so-called house-keeping protein that is essential to all cells for survival.”
Dr Hannan and his colleagues presented these findings in a poster at the AACR conference Hematologic Malignancies: Translating Discoveries to Novel Therapies.
The researchers previously showed that cancer cells are much more dependent on ribosome biogenesis than normal cells. And blocking the accelerated reading of ribosomal genes in mice—using CX5461—can cause lymphoma and leukemia cells to die, while sparing normal cells.
With their latest research, the group expanded upon these findings by testing CX-5461 in MLL-driven AML, V*κ-Myc-driven MM, and Eμ-Myc lymphoma.
They found that CX-5461 improved overall survival in MLL/ENL Nras leukemic mice, compared to placebo and standard therapy. The median survival was 17 days for vehicle-treated mice, 21 days for mice treated with cytarabine and doxorubicin, and 36 days for mice that received CX-5461 (P<0.0001 for vehicle vs CX-5461).
CX-5461 treated MLL-driven AML by inducing apoptosis, delaying cell-cycle progression, and promoting differentiation.
The researchers also found the therapeutic benefit of CX-5461 is not p53-dependent, which contradicts their previous findings. Human AML cell lines and primary patient samples were sensitive to CX-5461 independent of p53 status.
And MLL/ENL Nras p53-/- leukemic mice had significantly prolonged survival when treated with CX-5461, compared to vehicle-treated controls. The median survival was 11 days and 24 days, respectively (P<0.0001).
Likewise, CX-5461 significantly prolonged survival in mice bearing V*κ-Myc MM. The median survival was 103.5 days for controls and 175 days for mice that received CX-5461 (P<0.0001).
Finally, the researchers showed that CX-5461 synergizes with everolimus to treat Eμ-Myc lymphoma. The median survival was 15 days in control mice, 18 days in mice that received everolimus, 32 days in mice treated with CX-5461, and 54 days in mice that received both drugs (P<0.0001 for CX-5461 vs the combination).
“These results provide further rationale for the first-in-human phase 1 clinical trial that we initiated in July 2013 testing CX-5461 for patients with advanced hematological malignancies, including AML and multiple myeloma,” Dr Hannan said.
His group’s preclinical research was funded by the National Health and Medical Research Council, Australia; the Leukaemia Foundation of Australia; and Cancer Council Victoria, Melbourne, Australia. Senhwa Biosciences, the makers of CX-5461, provided the drug.
PHILADELPHIA—A drug that targets the ribosome may be active in a broad range of hematologic malignancies, researchers say.
The drug, CX-5461, inhibits the protein RNA polymerase I (Pol I), which is consistently upregulated in hematologic and other cancers.
CX-5461 significantly prolonged survival in mouse models of refractory acute myeloid leukemia (AML) and multiple myeloma (MM). It also synergized with everolimus to extend survival in mice with B-cell lymphoma.
Furthermore, the drug did not elicit severe adverse effects.
“We were excited to find that therapeutic doses of CX-5461 had little effect on normal cells in our experiments,” said Ross D. Hannan, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Australia,
“Prior to these studies, few people would have guessed that such a therapeutic window could be obtained by targeting a so-called house-keeping protein that is essential to all cells for survival.”
Dr Hannan and his colleagues presented these findings in a poster at the AACR conference Hematologic Malignancies: Translating Discoveries to Novel Therapies.
The researchers previously showed that cancer cells are much more dependent on ribosome biogenesis than normal cells. And blocking the accelerated reading of ribosomal genes in mice—using CX5461—can cause lymphoma and leukemia cells to die, while sparing normal cells.
With their latest research, the group expanded upon these findings by testing CX-5461 in MLL-driven AML, V*κ-Myc-driven MM, and Eμ-Myc lymphoma.
They found that CX-5461 improved overall survival in MLL/ENL Nras leukemic mice, compared to placebo and standard therapy. The median survival was 17 days for vehicle-treated mice, 21 days for mice treated with cytarabine and doxorubicin, and 36 days for mice that received CX-5461 (P<0.0001 for vehicle vs CX-5461).
CX-5461 treated MLL-driven AML by inducing apoptosis, delaying cell-cycle progression, and promoting differentiation.
The researchers also found the therapeutic benefit of CX-5461 is not p53-dependent, which contradicts their previous findings. Human AML cell lines and primary patient samples were sensitive to CX-5461 independent of p53 status.
And MLL/ENL Nras p53-/- leukemic mice had significantly prolonged survival when treated with CX-5461, compared to vehicle-treated controls. The median survival was 11 days and 24 days, respectively (P<0.0001).
Likewise, CX-5461 significantly prolonged survival in mice bearing V*κ-Myc MM. The median survival was 103.5 days for controls and 175 days for mice that received CX-5461 (P<0.0001).
Finally, the researchers showed that CX-5461 synergizes with everolimus to treat Eμ-Myc lymphoma. The median survival was 15 days in control mice, 18 days in mice that received everolimus, 32 days in mice treated with CX-5461, and 54 days in mice that received both drugs (P<0.0001 for CX-5461 vs the combination).
“These results provide further rationale for the first-in-human phase 1 clinical trial that we initiated in July 2013 testing CX-5461 for patients with advanced hematological malignancies, including AML and multiple myeloma,” Dr Hannan said.
His group’s preclinical research was funded by the National Health and Medical Research Council, Australia; the Leukaemia Foundation of Australia; and Cancer Council Victoria, Melbourne, Australia. Senhwa Biosciences, the makers of CX-5461, provided the drug.
PHILADELPHIA—A drug that targets the ribosome may be active in a broad range of hematologic malignancies, researchers say.
The drug, CX-5461, inhibits the protein RNA polymerase I (Pol I), which is consistently upregulated in hematologic and other cancers.
CX-5461 significantly prolonged survival in mouse models of refractory acute myeloid leukemia (AML) and multiple myeloma (MM). It also synergized with everolimus to extend survival in mice with B-cell lymphoma.
Furthermore, the drug did not elicit severe adverse effects.
“We were excited to find that therapeutic doses of CX-5461 had little effect on normal cells in our experiments,” said Ross D. Hannan, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Australia,
“Prior to these studies, few people would have guessed that such a therapeutic window could be obtained by targeting a so-called house-keeping protein that is essential to all cells for survival.”
Dr Hannan and his colleagues presented these findings in a poster at the AACR conference Hematologic Malignancies: Translating Discoveries to Novel Therapies.
The researchers previously showed that cancer cells are much more dependent on ribosome biogenesis than normal cells. And blocking the accelerated reading of ribosomal genes in mice—using CX5461—can cause lymphoma and leukemia cells to die, while sparing normal cells.
With their latest research, the group expanded upon these findings by testing CX-5461 in MLL-driven AML, V*κ-Myc-driven MM, and Eμ-Myc lymphoma.
They found that CX-5461 improved overall survival in MLL/ENL Nras leukemic mice, compared to placebo and standard therapy. The median survival was 17 days for vehicle-treated mice, 21 days for mice treated with cytarabine and doxorubicin, and 36 days for mice that received CX-5461 (P<0.0001 for vehicle vs CX-5461).
CX-5461 treated MLL-driven AML by inducing apoptosis, delaying cell-cycle progression, and promoting differentiation.
The researchers also found the therapeutic benefit of CX-5461 is not p53-dependent, which contradicts their previous findings. Human AML cell lines and primary patient samples were sensitive to CX-5461 independent of p53 status.
And MLL/ENL Nras p53-/- leukemic mice had significantly prolonged survival when treated with CX-5461, compared to vehicle-treated controls. The median survival was 11 days and 24 days, respectively (P<0.0001).
Likewise, CX-5461 significantly prolonged survival in mice bearing V*κ-Myc MM. The median survival was 103.5 days for controls and 175 days for mice that received CX-5461 (P<0.0001).
Finally, the researchers showed that CX-5461 synergizes with everolimus to treat Eμ-Myc lymphoma. The median survival was 15 days in control mice, 18 days in mice that received everolimus, 32 days in mice treated with CX-5461, and 54 days in mice that received both drugs (P<0.0001 for CX-5461 vs the combination).
“These results provide further rationale for the first-in-human phase 1 clinical trial that we initiated in July 2013 testing CX-5461 for patients with advanced hematological malignancies, including AML and multiple myeloma,” Dr Hannan said.
His group’s preclinical research was funded by the National Health and Medical Research Council, Australia; the Leukaemia Foundation of Australia; and Cancer Council Victoria, Melbourne, Australia. Senhwa Biosciences, the makers of CX-5461, provided the drug.
PET-CT better predicted follicular lymphoma survival
F-18 positron emission tomography combined with low-dose computed tomography was more effective than conventional CT or the Follicular Lymphoma International Prognostic Index for predicting treatment response in patients with advanced follicular lymphoma, authors of a pooled analysis reported online in the Lancet Haemotology.
“Although these results are reassuring for patients who have a negative PET [positron emission tomography] scan, those who have a positive PET scan after first-line therapy can no longer be regarded as having an indolent disease and should be closely monitored,” wrote Dr. Judith Trotman at the University of Sydney, Australia, and her associates.
Follicular lymphoma often recurs after treatment, but predicting early relapsers has been a challenge, the investigators noted. They performed a masked review of three prospective, multicenter studies of 246 patients with follicular lymphoma, finding that patients with negative postinduction PET-CT scans (scores of less than four on the five-point Deauville scale) had median progression-free survival (PFS) of more than 6 years, compared with a median PFS of only 16.9 months for PET-positive patients (P = .0001). The markedly shorter PFS occurred even though most patients received anthracycline (CHOP/FM), the researchers said (Lancet Haematol. 2014 Sept. 18 [doi:10.1016/ S2352-3026(14)70008-0]).
Four years after induction, 63.4% of PET-negative patients were progression free, compared with only 23.2% of PET-positive patients (P less than .0001), the investigators added. And 4-year overall survival in PET-negative patients also was significantly higher than in PET-negative patients (97.1% vs. 87.2%; P less than .0001), they reported.PET status also was “much stronger” than the Follicular Lymphoma International Prognostic Index, FLIPI2, or contrast-enhanced CT for predicting outcomes in conventional responders, Dr. Trotman and her associates said. Conventional CT response only weakly predicted progression-free survival (P = .017), while a FLIPI2 score of 3-5 predicted progression-free survival (P = .011) but not overall survival. For this reason, responders historically have faced “an uncertain remission” and need close clinical follow-up, they pointed out.
The study was funded by the Lymphoma Study Association, Direction de la Recherche Clinique de l’Assistance Publique–Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health. Dr. Trotman reported uncompensated advisory relationships with Roche and Janssen, and three of 18 coauthors reported financial relationships with Merck, Celgene, Roche, Takeda, Janssen, and Spectrum. The rest reported having no conflicts of interest.
That patient outcome can be predicted with molecular imaging is good news: The question is, what should be done with this information? In clinical practice, patients with a positive scan could be followed up more closely. No data yet show that intervention with treatment after a positive PET result in patients with follicular lymphoma will improve outcome.
The results from Dr. Trotman and her colleagues might lead to several clinical research opportunities. One such possibility would be to assess if an early reaction to the PET scan result improves patient outcome. Thus, patients with a positive PET scan after induction therapy could be randomly assigned to either deferred treatment until disease progression or immediate intervention. A preferable alternative would be to introduce a unique agent at that time, such as the newly developed small molecules (including idelalisib, ibrutinib, or ABT-199) in a novel combination.
The most crucial need is to identify biomarkers that distinguish this group of patients from those whose PET scans become negative. Once that goal is achieved, that information could be used to develop new, targeted induction regimens that improve initial treatment of the disease and, as a result, increase the number of patients with negative PET scans.
Dr. Bruce Cheson is professor of medicine and director of hematology research at Georgetown University Hospital, Washington. He reported research funding from Pharmacyclics, Gilead, Celgene, Roche-Genentech, and AbbVie, and paid consulting relationships with Pharmacyclics, Seattle Genetics, Gilead, Celgene, Roche-Genentech, Spectrum, and Mundipharma. These remarks are taken from his accompanying editorial (Lancet Haematol. 2014 Sept. 18 [doi:10.1016/S2352-3026(14)70015-8]).
That patient outcome can be predicted with molecular imaging is good news: The question is, what should be done with this information? In clinical practice, patients with a positive scan could be followed up more closely. No data yet show that intervention with treatment after a positive PET result in patients with follicular lymphoma will improve outcome.
The results from Dr. Trotman and her colleagues might lead to several clinical research opportunities. One such possibility would be to assess if an early reaction to the PET scan result improves patient outcome. Thus, patients with a positive PET scan after induction therapy could be randomly assigned to either deferred treatment until disease progression or immediate intervention. A preferable alternative would be to introduce a unique agent at that time, such as the newly developed small molecules (including idelalisib, ibrutinib, or ABT-199) in a novel combination.
The most crucial need is to identify biomarkers that distinguish this group of patients from those whose PET scans become negative. Once that goal is achieved, that information could be used to develop new, targeted induction regimens that improve initial treatment of the disease and, as a result, increase the number of patients with negative PET scans.
Dr. Bruce Cheson is professor of medicine and director of hematology research at Georgetown University Hospital, Washington. He reported research funding from Pharmacyclics, Gilead, Celgene, Roche-Genentech, and AbbVie, and paid consulting relationships with Pharmacyclics, Seattle Genetics, Gilead, Celgene, Roche-Genentech, Spectrum, and Mundipharma. These remarks are taken from his accompanying editorial (Lancet Haematol. 2014 Sept. 18 [doi:10.1016/S2352-3026(14)70015-8]).
That patient outcome can be predicted with molecular imaging is good news: The question is, what should be done with this information? In clinical practice, patients with a positive scan could be followed up more closely. No data yet show that intervention with treatment after a positive PET result in patients with follicular lymphoma will improve outcome.
The results from Dr. Trotman and her colleagues might lead to several clinical research opportunities. One such possibility would be to assess if an early reaction to the PET scan result improves patient outcome. Thus, patients with a positive PET scan after induction therapy could be randomly assigned to either deferred treatment until disease progression or immediate intervention. A preferable alternative would be to introduce a unique agent at that time, such as the newly developed small molecules (including idelalisib, ibrutinib, or ABT-199) in a novel combination.
The most crucial need is to identify biomarkers that distinguish this group of patients from those whose PET scans become negative. Once that goal is achieved, that information could be used to develop new, targeted induction regimens that improve initial treatment of the disease and, as a result, increase the number of patients with negative PET scans.
Dr. Bruce Cheson is professor of medicine and director of hematology research at Georgetown University Hospital, Washington. He reported research funding from Pharmacyclics, Gilead, Celgene, Roche-Genentech, and AbbVie, and paid consulting relationships with Pharmacyclics, Seattle Genetics, Gilead, Celgene, Roche-Genentech, Spectrum, and Mundipharma. These remarks are taken from his accompanying editorial (Lancet Haematol. 2014 Sept. 18 [doi:10.1016/S2352-3026(14)70015-8]).
F-18 positron emission tomography combined with low-dose computed tomography was more effective than conventional CT or the Follicular Lymphoma International Prognostic Index for predicting treatment response in patients with advanced follicular lymphoma, authors of a pooled analysis reported online in the Lancet Haemotology.
“Although these results are reassuring for patients who have a negative PET [positron emission tomography] scan, those who have a positive PET scan after first-line therapy can no longer be regarded as having an indolent disease and should be closely monitored,” wrote Dr. Judith Trotman at the University of Sydney, Australia, and her associates.
Follicular lymphoma often recurs after treatment, but predicting early relapsers has been a challenge, the investigators noted. They performed a masked review of three prospective, multicenter studies of 246 patients with follicular lymphoma, finding that patients with negative postinduction PET-CT scans (scores of less than four on the five-point Deauville scale) had median progression-free survival (PFS) of more than 6 years, compared with a median PFS of only 16.9 months for PET-positive patients (P = .0001). The markedly shorter PFS occurred even though most patients received anthracycline (CHOP/FM), the researchers said (Lancet Haematol. 2014 Sept. 18 [doi:10.1016/ S2352-3026(14)70008-0]).
Four years after induction, 63.4% of PET-negative patients were progression free, compared with only 23.2% of PET-positive patients (P less than .0001), the investigators added. And 4-year overall survival in PET-negative patients also was significantly higher than in PET-negative patients (97.1% vs. 87.2%; P less than .0001), they reported.PET status also was “much stronger” than the Follicular Lymphoma International Prognostic Index, FLIPI2, or contrast-enhanced CT for predicting outcomes in conventional responders, Dr. Trotman and her associates said. Conventional CT response only weakly predicted progression-free survival (P = .017), while a FLIPI2 score of 3-5 predicted progression-free survival (P = .011) but not overall survival. For this reason, responders historically have faced “an uncertain remission” and need close clinical follow-up, they pointed out.
The study was funded by the Lymphoma Study Association, Direction de la Recherche Clinique de l’Assistance Publique–Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health. Dr. Trotman reported uncompensated advisory relationships with Roche and Janssen, and three of 18 coauthors reported financial relationships with Merck, Celgene, Roche, Takeda, Janssen, and Spectrum. The rest reported having no conflicts of interest.
F-18 positron emission tomography combined with low-dose computed tomography was more effective than conventional CT or the Follicular Lymphoma International Prognostic Index for predicting treatment response in patients with advanced follicular lymphoma, authors of a pooled analysis reported online in the Lancet Haemotology.
“Although these results are reassuring for patients who have a negative PET [positron emission tomography] scan, those who have a positive PET scan after first-line therapy can no longer be regarded as having an indolent disease and should be closely monitored,” wrote Dr. Judith Trotman at the University of Sydney, Australia, and her associates.
Follicular lymphoma often recurs after treatment, but predicting early relapsers has been a challenge, the investigators noted. They performed a masked review of three prospective, multicenter studies of 246 patients with follicular lymphoma, finding that patients with negative postinduction PET-CT scans (scores of less than four on the five-point Deauville scale) had median progression-free survival (PFS) of more than 6 years, compared with a median PFS of only 16.9 months for PET-positive patients (P = .0001). The markedly shorter PFS occurred even though most patients received anthracycline (CHOP/FM), the researchers said (Lancet Haematol. 2014 Sept. 18 [doi:10.1016/ S2352-3026(14)70008-0]).
Four years after induction, 63.4% of PET-negative patients were progression free, compared with only 23.2% of PET-positive patients (P less than .0001), the investigators added. And 4-year overall survival in PET-negative patients also was significantly higher than in PET-negative patients (97.1% vs. 87.2%; P less than .0001), they reported.PET status also was “much stronger” than the Follicular Lymphoma International Prognostic Index, FLIPI2, or contrast-enhanced CT for predicting outcomes in conventional responders, Dr. Trotman and her associates said. Conventional CT response only weakly predicted progression-free survival (P = .017), while a FLIPI2 score of 3-5 predicted progression-free survival (P = .011) but not overall survival. For this reason, responders historically have faced “an uncertain remission” and need close clinical follow-up, they pointed out.
The study was funded by the Lymphoma Study Association, Direction de la Recherche Clinique de l’Assistance Publique–Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health. Dr. Trotman reported uncompensated advisory relationships with Roche and Janssen, and three of 18 coauthors reported financial relationships with Merck, Celgene, Roche, Takeda, Janssen, and Spectrum. The rest reported having no conflicts of interest.
Key clinical point: In patients with follicular lymphoma, PET-CT was better than conventional CT for assessing response and survival after first-line chemoimmunotherapy.
Major finding: Patients with positive postinduction PET scans were significantly less likely to be progression free at 4 years, compared with PET-negative patients (23.2% vs. 63.4%, P less than .0001), and had significantly lower 4-year overall survival (87.2% vs. 97.1%; P less than .0001).
Data source: Masked review of three multicenter prospective studies of 246 patients with follicular lymphoma who underwent postinduction PET-CT according to the five-point Deauville scale.
Disclosures: The study was funded by the Lymphoma Study Association, Direction de la Recherche Clinique de l’Assistance Publique–Hôpitaux de Paris, Fondazione Italiana Linfomi, and the Italian Ministry of Health. Dr. Trotman reported uncompensated advisory relationships with Roche and Janssen, and three of 18 coauthors reported financial relationships with Merck, Celgene, Roche, Takeda, Janssen, and Spectrum. The rest reported having no conflicts of interest.
Practice gaps and barriers to optimal care of hematologic malignancies in the United States
Objective To identify clinical challenges among hematologists and medical oncologists regarding the provision of care to patients with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), or B-cell lymphomas.
Methods Hematologists and medical oncologists in active practice in the United States and who have a case load of ≥ 1 patient a year with CML, ALL, or B-cell lymphoma were recruited. The initial qualitative phase consisted of an online case-based survey followed by an interview exploring the contextual and behavioral factors that influence treatment decisions (n = 27). The analysis of qualitative data then informed a quantitative phase, in which 121 participants completed an online survey composed of case vignettes, multiple choice, and semantic differential rating scale questions. The respondents’ answers were compared with recommendations from treatment guidelines and faculty experts.
Results A higher frequency of bone marrow biopsies was reported compared with expert faculty recommendations by 74% of oncologists. Many respondents failed to recognize the clinical relevance of BCR-ABL mutations other than T315I. Respondents reported perceiving difficulties in individualizing treatment and interpreting response to treatment in patients with ALL and B-cell lymphomas. Fewer than 30% of respondents recognized the mechanisms of action of 5 of the 9 promising investigational agents presented.
Limitations Participant self-selection bias is a possibility because participation was voluntary. Practice gaps are not based on clinical data, but hypothetical case situations and self-report.
Conclusions Findings from this study can guide education to address the identified challenges in caring for patients with hematologic malignancies and improving patient care.
Funding This needs assessment was financially supported with an educational research grant from Pfizer Medical Education Group to the Annenberg Center for Health Sciences at Eisenhower.
Click on the PDF icon at the top of this introduction to read the full article.
Objective To identify clinical challenges among hematologists and medical oncologists regarding the provision of care to patients with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), or B-cell lymphomas.
Methods Hematologists and medical oncologists in active practice in the United States and who have a case load of ≥ 1 patient a year with CML, ALL, or B-cell lymphoma were recruited. The initial qualitative phase consisted of an online case-based survey followed by an interview exploring the contextual and behavioral factors that influence treatment decisions (n = 27). The analysis of qualitative data then informed a quantitative phase, in which 121 participants completed an online survey composed of case vignettes, multiple choice, and semantic differential rating scale questions. The respondents’ answers were compared with recommendations from treatment guidelines and faculty experts.
Results A higher frequency of bone marrow biopsies was reported compared with expert faculty recommendations by 74% of oncologists. Many respondents failed to recognize the clinical relevance of BCR-ABL mutations other than T315I. Respondents reported perceiving difficulties in individualizing treatment and interpreting response to treatment in patients with ALL and B-cell lymphomas. Fewer than 30% of respondents recognized the mechanisms of action of 5 of the 9 promising investigational agents presented.
Limitations Participant self-selection bias is a possibility because participation was voluntary. Practice gaps are not based on clinical data, but hypothetical case situations and self-report.
Conclusions Findings from this study can guide education to address the identified challenges in caring for patients with hematologic malignancies and improving patient care.
Funding This needs assessment was financially supported with an educational research grant from Pfizer Medical Education Group to the Annenberg Center for Health Sciences at Eisenhower.
Click on the PDF icon at the top of this introduction to read the full article.
Objective To identify clinical challenges among hematologists and medical oncologists regarding the provision of care to patients with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), or B-cell lymphomas.
Methods Hematologists and medical oncologists in active practice in the United States and who have a case load of ≥ 1 patient a year with CML, ALL, or B-cell lymphoma were recruited. The initial qualitative phase consisted of an online case-based survey followed by an interview exploring the contextual and behavioral factors that influence treatment decisions (n = 27). The analysis of qualitative data then informed a quantitative phase, in which 121 participants completed an online survey composed of case vignettes, multiple choice, and semantic differential rating scale questions. The respondents’ answers were compared with recommendations from treatment guidelines and faculty experts.
Results A higher frequency of bone marrow biopsies was reported compared with expert faculty recommendations by 74% of oncologists. Many respondents failed to recognize the clinical relevance of BCR-ABL mutations other than T315I. Respondents reported perceiving difficulties in individualizing treatment and interpreting response to treatment in patients with ALL and B-cell lymphomas. Fewer than 30% of respondents recognized the mechanisms of action of 5 of the 9 promising investigational agents presented.
Limitations Participant self-selection bias is a possibility because participation was voluntary. Practice gaps are not based on clinical data, but hypothetical case situations and self-report.
Conclusions Findings from this study can guide education to address the identified challenges in caring for patients with hematologic malignancies and improving patient care.
Funding This needs assessment was financially supported with an educational research grant from Pfizer Medical Education Group to the Annenberg Center for Health Sciences at Eisenhower.
Click on the PDF icon at the top of this introduction to read the full article.
Exercise boosts anticancer effects of doxorubicin
Credit: Aaron Logan
Exercising during doxorubicin treatment can amplify the drug’s cancer-fighting ability, according to preclinical research.
Previous studies showed that adopting an exercise regimen before receiving doxorubicin could protect against the cardiac side effects associated with the drug.
Now, researchers have reported that exercising during doxorubicin treatment does not protect the heart, but it does help shrink tumors in mice.
Joseph Libonati, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues reported these findings in the American Journal of Physiology—Regulatory, Integrative and Comparative Physiology.
The researchers conducted experiments with 4 groups of mice, all of which received an injection of melanoma cells.
During the next 2 weeks, 2 of the groups received doxorubicin in 2 doses, while the other 2 groups received placebo injections.
A treated group and a placebo group were put on exercise regimens, walking for 45 minutes 5 days a week on mouse-sized treadmills, while the rest of the mice remained sedentary.
After the 2-week trial, the researchers examined the animals’ hearts using echocardiogram and tissue analysis.
As expected, doxorubicin reduced the heart’s function and size and increased fibrosis. Mice that exercised were not protected from this damage.
“We looked, and the exercise didn’t do anything to the heart; it didn’t worsen it, it didn’t help it,” Dr Libonati said. “But the tumor data—I find them actually amazing.”
The mice that received doxorubicin and exercised had significantly smaller tumors after 2 weeks than mice that only received doxorubicin (P<0.05).
Further studies will investigate exactly how exercise enhances the effect of doxorubicin, but the researchers believe it could be, in part, because exercise increases blood flow to the tumor, bringing with it more of the drug in the bloodstream.
“If exercise helps in this way, you could potentially use a smaller dose of the drug and get fewer side effects,” Dr Libonati said.
Gaining a clearer understanding of the many ways that exercise affects various systems of the body could also pave the way for developing drugs that mimic the effects of exercise.
“People don’t take a drug and then sit down all day,” Dr Libonati said. “Something as simple as moving affects how drugs are metabolized. We’re only just beginning to understand the complexities.”
Credit: Aaron Logan
Exercising during doxorubicin treatment can amplify the drug’s cancer-fighting ability, according to preclinical research.
Previous studies showed that adopting an exercise regimen before receiving doxorubicin could protect against the cardiac side effects associated with the drug.
Now, researchers have reported that exercising during doxorubicin treatment does not protect the heart, but it does help shrink tumors in mice.
Joseph Libonati, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues reported these findings in the American Journal of Physiology—Regulatory, Integrative and Comparative Physiology.
The researchers conducted experiments with 4 groups of mice, all of which received an injection of melanoma cells.
During the next 2 weeks, 2 of the groups received doxorubicin in 2 doses, while the other 2 groups received placebo injections.
A treated group and a placebo group were put on exercise regimens, walking for 45 minutes 5 days a week on mouse-sized treadmills, while the rest of the mice remained sedentary.
After the 2-week trial, the researchers examined the animals’ hearts using echocardiogram and tissue analysis.
As expected, doxorubicin reduced the heart’s function and size and increased fibrosis. Mice that exercised were not protected from this damage.
“We looked, and the exercise didn’t do anything to the heart; it didn’t worsen it, it didn’t help it,” Dr Libonati said. “But the tumor data—I find them actually amazing.”
The mice that received doxorubicin and exercised had significantly smaller tumors after 2 weeks than mice that only received doxorubicin (P<0.05).
Further studies will investigate exactly how exercise enhances the effect of doxorubicin, but the researchers believe it could be, in part, because exercise increases blood flow to the tumor, bringing with it more of the drug in the bloodstream.
“If exercise helps in this way, you could potentially use a smaller dose of the drug and get fewer side effects,” Dr Libonati said.
Gaining a clearer understanding of the many ways that exercise affects various systems of the body could also pave the way for developing drugs that mimic the effects of exercise.
“People don’t take a drug and then sit down all day,” Dr Libonati said. “Something as simple as moving affects how drugs are metabolized. We’re only just beginning to understand the complexities.”
Credit: Aaron Logan
Exercising during doxorubicin treatment can amplify the drug’s cancer-fighting ability, according to preclinical research.
Previous studies showed that adopting an exercise regimen before receiving doxorubicin could protect against the cardiac side effects associated with the drug.
Now, researchers have reported that exercising during doxorubicin treatment does not protect the heart, but it does help shrink tumors in mice.
Joseph Libonati, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues reported these findings in the American Journal of Physiology—Regulatory, Integrative and Comparative Physiology.
The researchers conducted experiments with 4 groups of mice, all of which received an injection of melanoma cells.
During the next 2 weeks, 2 of the groups received doxorubicin in 2 doses, while the other 2 groups received placebo injections.
A treated group and a placebo group were put on exercise regimens, walking for 45 minutes 5 days a week on mouse-sized treadmills, while the rest of the mice remained sedentary.
After the 2-week trial, the researchers examined the animals’ hearts using echocardiogram and tissue analysis.
As expected, doxorubicin reduced the heart’s function and size and increased fibrosis. Mice that exercised were not protected from this damage.
“We looked, and the exercise didn’t do anything to the heart; it didn’t worsen it, it didn’t help it,” Dr Libonati said. “But the tumor data—I find them actually amazing.”
The mice that received doxorubicin and exercised had significantly smaller tumors after 2 weeks than mice that only received doxorubicin (P<0.05).
Further studies will investigate exactly how exercise enhances the effect of doxorubicin, but the researchers believe it could be, in part, because exercise increases blood flow to the tumor, bringing with it more of the drug in the bloodstream.
“If exercise helps in this way, you could potentially use a smaller dose of the drug and get fewer side effects,” Dr Libonati said.
Gaining a clearer understanding of the many ways that exercise affects various systems of the body could also pave the way for developing drugs that mimic the effects of exercise.
“People don’t take a drug and then sit down all day,” Dr Libonati said. “Something as simple as moving affects how drugs are metabolized. We’re only just beginning to understand the complexities.”