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FDA approves new drug for CLL/SLL and follicular lymphoma
The Food and Drug Administration has approved duvelisib (Copiktra), a dual PI3K delta/gamma inhibitor, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma.
who have received at least two prior therapies. Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.
Accelerated approval is based on a surrogate or intermediate endpoint – in this case, overall response rate – that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.
Duvelisib will be available in the U.S. immediately, according to Verastem, the company marketing the drug. The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug – infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.
The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.
The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. The DUO trial included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2,000 mg).
Efficacy results are based on patients who had received at least two prior therapies, including 95 patients in the duvelisib arm and 101 in the ofatumumab arm. The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.
The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab.
The safety results include all patients treated with duvelisib or ofatumumab in this trial. In the duvelisib arm, 12% of patients had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab. Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection and diarrhea/colitis. The DYNAMO trial enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy. There were 83 patients with FL.
Patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.
The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.
Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.
Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.
The Food and Drug Administration has approved duvelisib (Copiktra), a dual PI3K delta/gamma inhibitor, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma.
who have received at least two prior therapies. Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.
Accelerated approval is based on a surrogate or intermediate endpoint – in this case, overall response rate – that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.
Duvelisib will be available in the U.S. immediately, according to Verastem, the company marketing the drug. The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug – infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.
The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.
The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. The DUO trial included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2,000 mg).
Efficacy results are based on patients who had received at least two prior therapies, including 95 patients in the duvelisib arm and 101 in the ofatumumab arm. The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.
The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab.
The safety results include all patients treated with duvelisib or ofatumumab in this trial. In the duvelisib arm, 12% of patients had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab. Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection and diarrhea/colitis. The DYNAMO trial enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy. There were 83 patients with FL.
Patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.
The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.
Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.
Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.
The Food and Drug Administration has approved duvelisib (Copiktra), a dual PI3K delta/gamma inhibitor, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma.
who have received at least two prior therapies. Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.
Accelerated approval is based on a surrogate or intermediate endpoint – in this case, overall response rate – that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.
Duvelisib will be available in the U.S. immediately, according to Verastem, the company marketing the drug. The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug – infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.
The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.
The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. The DUO trial included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2,000 mg).
Efficacy results are based on patients who had received at least two prior therapies, including 95 patients in the duvelisib arm and 101 in the ofatumumab arm. The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.
The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab.
The safety results include all patients treated with duvelisib or ofatumumab in this trial. In the duvelisib arm, 12% of patients had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab. Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection and diarrhea/colitis. The DYNAMO trial enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy. There were 83 patients with FL.
Patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.
The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.
Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.
Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.
NICE looks likely to reject use of Kymriah for DLBCL
The National Institute for Health and Care Excellence (NICE) has issued draft guidance recommending against tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).
Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.
Tisagenlecleucel is also European Commission–approved to treat patients up to age 25 years who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse posttransplant, or in second or later relapse.
In September 2018, the National Health Service (NHS) in England announced tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.
However, in who have received two or more lines of systemic therapy. NICE noted that there is no standard treatment for this patient group, and that salvage chemotherapy is the most common treatment option.
Although the latest results from the JULIET trial suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy. Additionally, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.
All cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.
The list price for tisagenlecleucel is 282,000 pounds. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.
In August, NICE issued a similar draft guidance document recommending against use of another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta). Axicabtagene ciloleucel is approved in Europe for the treatment of patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.
The National Institute for Health and Care Excellence (NICE) has issued draft guidance recommending against tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).
Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.
Tisagenlecleucel is also European Commission–approved to treat patients up to age 25 years who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse posttransplant, or in second or later relapse.
In September 2018, the National Health Service (NHS) in England announced tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.
However, in who have received two or more lines of systemic therapy. NICE noted that there is no standard treatment for this patient group, and that salvage chemotherapy is the most common treatment option.
Although the latest results from the JULIET trial suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy. Additionally, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.
All cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.
The list price for tisagenlecleucel is 282,000 pounds. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.
In August, NICE issued a similar draft guidance document recommending against use of another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta). Axicabtagene ciloleucel is approved in Europe for the treatment of patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.
The National Institute for Health and Care Excellence (NICE) has issued draft guidance recommending against tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).
Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.
Tisagenlecleucel is also European Commission–approved to treat patients up to age 25 years who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse posttransplant, or in second or later relapse.
In September 2018, the National Health Service (NHS) in England announced tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.
However, in who have received two or more lines of systemic therapy. NICE noted that there is no standard treatment for this patient group, and that salvage chemotherapy is the most common treatment option.
Although the latest results from the JULIET trial suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy. Additionally, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.
All cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.
The list price for tisagenlecleucel is 282,000 pounds. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.
In August, NICE issued a similar draft guidance document recommending against use of another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta). Axicabtagene ciloleucel is approved in Europe for the treatment of patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.
Best practices defined for proton therapy in mediastinal lymphomas
Proton therapy can help mitigate toxicity in adults with mediastinal lymphomas, but only when this modality offers a clear advantage over intensity-modulated radiotherapy, according to new guidelines from the International Lymphoma Radiation Oncology Group.
Proton therapy reduces radiation dose to organs at risk in certain clinical presentations, such as when the mediastinal target is on both sides of the heart. The advantages are not always clear in other situations, such as when the target spans the right side of the heart, or when the target is above the heart with no axillary involvement, according to guideline authors Bouthaina Dabaja, MD, professor and section chief of hematology in the department of radiation oncology at the University of Texas MD Anderson Cancer Center, Houston, and her colleagues.
“The limited availability of proton therapy calls for case selection based on a clear understanding of which cases will derive most benefit from proton therapy as compared to advanced photon techniques,” Dr. Dabaja and her coauthors said in the guidelines, which were published in the journal Blood (doi: 10.1182/blood-2018-03-837633).
Along with intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy, proton therapy presents “another opportunity” for more conformal dose distribution and better sparing of organs at risk, according to the consensus recommendations. Proton therapy can greatly benefit certain patients with mediastinal disease. These include young female patients to reduce breast dose and risk of a secondary breast cancer, patients at high risk of radiation-related toxicity due to previous treatment, and patients with disease spanning below the origin of the left main stem coronary artery that is anterior to, posterior to, or on the left side of the heart.
“The relation of disease to organs at risk determines the situations in which proton therapy is most beneficial,” the experts said in the guidelines. However, the consideration of proton therapy needs to factor the complexities of proton therapy planning, the need to manage uncertainties, and the “evolving nature of the technology,” which includes the development of pencil beam scanning.
While passive scattering proton therapy (PSPT) is the least complex delivery technique, it is challenging because beams can conform only to one side of the target; by contrast, the experts said, active mode pencil beam scanning proton therapy (PBSPT) potentially provides better conformity and sparing of organs at risk.
“Because treatment involves delivery of individual controlled spots, inhomogenous doses can be created deliberately,” the guideline authors said in their report.
However, motion management is “of prime importance” with PBSPT, which is more sensitive to density changes in the beam path as compared to PSPT, they added. Toward that end, physicians should pay close attention to evaluating intrafractional movement, which is frequently tied to the breathing cycle.
The guidelines list a total of 11 authors representing The University of Texas MD Anderson Cancer Center; University of Florida, Jacksonville; University of Pennsylvania, Philadelphia; University of Louisiana, Baton Rouge; Proton Therapy Center Czech, Prague; Motol University Hospital, Czech Republic; St. Thomas and Guy Hospital, London; Institut Curie, Paris; and Rigshospitalet, Copenhagen.
Dr. Dabaja and her guideline coauthors reported no funding or conflicts of interest.
Proton therapy can help mitigate toxicity in adults with mediastinal lymphomas, but only when this modality offers a clear advantage over intensity-modulated radiotherapy, according to new guidelines from the International Lymphoma Radiation Oncology Group.
Proton therapy reduces radiation dose to organs at risk in certain clinical presentations, such as when the mediastinal target is on both sides of the heart. The advantages are not always clear in other situations, such as when the target spans the right side of the heart, or when the target is above the heart with no axillary involvement, according to guideline authors Bouthaina Dabaja, MD, professor and section chief of hematology in the department of radiation oncology at the University of Texas MD Anderson Cancer Center, Houston, and her colleagues.
“The limited availability of proton therapy calls for case selection based on a clear understanding of which cases will derive most benefit from proton therapy as compared to advanced photon techniques,” Dr. Dabaja and her coauthors said in the guidelines, which were published in the journal Blood (doi: 10.1182/blood-2018-03-837633).
Along with intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy, proton therapy presents “another opportunity” for more conformal dose distribution and better sparing of organs at risk, according to the consensus recommendations. Proton therapy can greatly benefit certain patients with mediastinal disease. These include young female patients to reduce breast dose and risk of a secondary breast cancer, patients at high risk of radiation-related toxicity due to previous treatment, and patients with disease spanning below the origin of the left main stem coronary artery that is anterior to, posterior to, or on the left side of the heart.
“The relation of disease to organs at risk determines the situations in which proton therapy is most beneficial,” the experts said in the guidelines. However, the consideration of proton therapy needs to factor the complexities of proton therapy planning, the need to manage uncertainties, and the “evolving nature of the technology,” which includes the development of pencil beam scanning.
While passive scattering proton therapy (PSPT) is the least complex delivery technique, it is challenging because beams can conform only to one side of the target; by contrast, the experts said, active mode pencil beam scanning proton therapy (PBSPT) potentially provides better conformity and sparing of organs at risk.
“Because treatment involves delivery of individual controlled spots, inhomogenous doses can be created deliberately,” the guideline authors said in their report.
However, motion management is “of prime importance” with PBSPT, which is more sensitive to density changes in the beam path as compared to PSPT, they added. Toward that end, physicians should pay close attention to evaluating intrafractional movement, which is frequently tied to the breathing cycle.
The guidelines list a total of 11 authors representing The University of Texas MD Anderson Cancer Center; University of Florida, Jacksonville; University of Pennsylvania, Philadelphia; University of Louisiana, Baton Rouge; Proton Therapy Center Czech, Prague; Motol University Hospital, Czech Republic; St. Thomas and Guy Hospital, London; Institut Curie, Paris; and Rigshospitalet, Copenhagen.
Dr. Dabaja and her guideline coauthors reported no funding or conflicts of interest.
Proton therapy can help mitigate toxicity in adults with mediastinal lymphomas, but only when this modality offers a clear advantage over intensity-modulated radiotherapy, according to new guidelines from the International Lymphoma Radiation Oncology Group.
Proton therapy reduces radiation dose to organs at risk in certain clinical presentations, such as when the mediastinal target is on both sides of the heart. The advantages are not always clear in other situations, such as when the target spans the right side of the heart, or when the target is above the heart with no axillary involvement, according to guideline authors Bouthaina Dabaja, MD, professor and section chief of hematology in the department of radiation oncology at the University of Texas MD Anderson Cancer Center, Houston, and her colleagues.
“The limited availability of proton therapy calls for case selection based on a clear understanding of which cases will derive most benefit from proton therapy as compared to advanced photon techniques,” Dr. Dabaja and her coauthors said in the guidelines, which were published in the journal Blood (doi: 10.1182/blood-2018-03-837633).
Along with intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy, proton therapy presents “another opportunity” for more conformal dose distribution and better sparing of organs at risk, according to the consensus recommendations. Proton therapy can greatly benefit certain patients with mediastinal disease. These include young female patients to reduce breast dose and risk of a secondary breast cancer, patients at high risk of radiation-related toxicity due to previous treatment, and patients with disease spanning below the origin of the left main stem coronary artery that is anterior to, posterior to, or on the left side of the heart.
“The relation of disease to organs at risk determines the situations in which proton therapy is most beneficial,” the experts said in the guidelines. However, the consideration of proton therapy needs to factor the complexities of proton therapy planning, the need to manage uncertainties, and the “evolving nature of the technology,” which includes the development of pencil beam scanning.
While passive scattering proton therapy (PSPT) is the least complex delivery technique, it is challenging because beams can conform only to one side of the target; by contrast, the experts said, active mode pencil beam scanning proton therapy (PBSPT) potentially provides better conformity and sparing of organs at risk.
“Because treatment involves delivery of individual controlled spots, inhomogenous doses can be created deliberately,” the guideline authors said in their report.
However, motion management is “of prime importance” with PBSPT, which is more sensitive to density changes in the beam path as compared to PSPT, they added. Toward that end, physicians should pay close attention to evaluating intrafractional movement, which is frequently tied to the breathing cycle.
The guidelines list a total of 11 authors representing The University of Texas MD Anderson Cancer Center; University of Florida, Jacksonville; University of Pennsylvania, Philadelphia; University of Louisiana, Baton Rouge; Proton Therapy Center Czech, Prague; Motol University Hospital, Czech Republic; St. Thomas and Guy Hospital, London; Institut Curie, Paris; and Rigshospitalet, Copenhagen.
Dr. Dabaja and her guideline coauthors reported no funding or conflicts of interest.
FROM BLOOD
Be wary of watchful waiting in follicular lymphoma
A substantial proportion of patients with follicular lymphoma managed with watchful waiting develop organ dysfunction or transformation that may negatively impact survival outcomes, results of a retrospective study suggest.
About one-quarter of patients managed with watchful waiting developed significant organ dysfunction or transformation at first progression over 8.2 years of follow-up.
Organ dysfunction and transformation were associated with significantly worse overall survival that could not be predicted based on baseline characteristics, the study authors reported in Clinical Lymphoma, Myeloma & Leukemia.
The study confirmed certain benefits of watchful waiting, including a low risk of progression and an “excellent” rate of overall survival, the investigators said.
However, the substantial rate of organ dysfunction and transformation in a subset of patients is “clinically meaningful for informed decision making,” reported Gwynivere A. Davies, MD, of the University of Calgary (Alta.), and her coauthors.
“While consenting patients to initial [watchful waiting], patients need to be informed about the risk for these adverse events, as well as receiving education and the need for close monitoring regarding symptoms that may indicate serious progression events,” Dr. Davies and her coauthors wrote.
Alternatively, rituximab chemotherapy, with or without rituximab maintenance, might be warranted for watchful waiting patients with clear disease progression before organ dysfunction or transformation events, despite not meeting high-tumor burden therapy indications.
The retrospective study included data from the Alberta Lymphoma Database on patients with grade 1-3a follicular lymphoma aged 18-70 years who were diagnosed between 1994 and 2011. Investigators identified 238 patients initially managed with watchful waiting, with a median age of 54.1 years at diagnosis. More than 80% were advanced stage.
Only 71% of these patients progressed, with a median time to progression of about 30 months and a 10-year survival rate from diagnosis of 81.2%, investigators said. However, 58 patients (24.4%) had organ dysfunction or transformation at the time of progression.
Those adverse outcomes significantly affected overall survival. The 10-year overall survival was 65.4% for patients with transformation at progression versus 83.2% for those without (P = .0017). Likewise, 10-year overall survival was 71.5% and 82.7%, respectively, for those with organ dysfunction at progression and those without (P = .028).
Investigators also looked at a comparison group of 236 follicular lymphoma patients managed with immediate rituximab chemotherapy. They found survival outcomes in that group were similar to those in the subgroup of 56 watchful waiting patients who received primarily rituximab-containing regimens at the time of organ dysfunction or transformation.
Taken together, the findings suggest management changes may be warranted for follicular lymphoma patients managed according to a watchful waiting strategy, the investigators wrote. “Consideration should be given to implementing standardized follow-up imaging, with early initiation of rituximab-based therapy if there is evidence of progression in an attempt to prevent these potentially clinically impactful events.”
Dr. Davies reported having no financial disclosures. Study coauthors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.
SOURCE: Davies GA et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 28. doi: 10.1016/j.clml.2018.08.015.
A substantial proportion of patients with follicular lymphoma managed with watchful waiting develop organ dysfunction or transformation that may negatively impact survival outcomes, results of a retrospective study suggest.
About one-quarter of patients managed with watchful waiting developed significant organ dysfunction or transformation at first progression over 8.2 years of follow-up.
Organ dysfunction and transformation were associated with significantly worse overall survival that could not be predicted based on baseline characteristics, the study authors reported in Clinical Lymphoma, Myeloma & Leukemia.
The study confirmed certain benefits of watchful waiting, including a low risk of progression and an “excellent” rate of overall survival, the investigators said.
However, the substantial rate of organ dysfunction and transformation in a subset of patients is “clinically meaningful for informed decision making,” reported Gwynivere A. Davies, MD, of the University of Calgary (Alta.), and her coauthors.
“While consenting patients to initial [watchful waiting], patients need to be informed about the risk for these adverse events, as well as receiving education and the need for close monitoring regarding symptoms that may indicate serious progression events,” Dr. Davies and her coauthors wrote.
Alternatively, rituximab chemotherapy, with or without rituximab maintenance, might be warranted for watchful waiting patients with clear disease progression before organ dysfunction or transformation events, despite not meeting high-tumor burden therapy indications.
The retrospective study included data from the Alberta Lymphoma Database on patients with grade 1-3a follicular lymphoma aged 18-70 years who were diagnosed between 1994 and 2011. Investigators identified 238 patients initially managed with watchful waiting, with a median age of 54.1 years at diagnosis. More than 80% were advanced stage.
Only 71% of these patients progressed, with a median time to progression of about 30 months and a 10-year survival rate from diagnosis of 81.2%, investigators said. However, 58 patients (24.4%) had organ dysfunction or transformation at the time of progression.
Those adverse outcomes significantly affected overall survival. The 10-year overall survival was 65.4% for patients with transformation at progression versus 83.2% for those without (P = .0017). Likewise, 10-year overall survival was 71.5% and 82.7%, respectively, for those with organ dysfunction at progression and those without (P = .028).
Investigators also looked at a comparison group of 236 follicular lymphoma patients managed with immediate rituximab chemotherapy. They found survival outcomes in that group were similar to those in the subgroup of 56 watchful waiting patients who received primarily rituximab-containing regimens at the time of organ dysfunction or transformation.
Taken together, the findings suggest management changes may be warranted for follicular lymphoma patients managed according to a watchful waiting strategy, the investigators wrote. “Consideration should be given to implementing standardized follow-up imaging, with early initiation of rituximab-based therapy if there is evidence of progression in an attempt to prevent these potentially clinically impactful events.”
Dr. Davies reported having no financial disclosures. Study coauthors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.
SOURCE: Davies GA et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 28. doi: 10.1016/j.clml.2018.08.015.
A substantial proportion of patients with follicular lymphoma managed with watchful waiting develop organ dysfunction or transformation that may negatively impact survival outcomes, results of a retrospective study suggest.
About one-quarter of patients managed with watchful waiting developed significant organ dysfunction or transformation at first progression over 8.2 years of follow-up.
Organ dysfunction and transformation were associated with significantly worse overall survival that could not be predicted based on baseline characteristics, the study authors reported in Clinical Lymphoma, Myeloma & Leukemia.
The study confirmed certain benefits of watchful waiting, including a low risk of progression and an “excellent” rate of overall survival, the investigators said.
However, the substantial rate of organ dysfunction and transformation in a subset of patients is “clinically meaningful for informed decision making,” reported Gwynivere A. Davies, MD, of the University of Calgary (Alta.), and her coauthors.
“While consenting patients to initial [watchful waiting], patients need to be informed about the risk for these adverse events, as well as receiving education and the need for close monitoring regarding symptoms that may indicate serious progression events,” Dr. Davies and her coauthors wrote.
Alternatively, rituximab chemotherapy, with or without rituximab maintenance, might be warranted for watchful waiting patients with clear disease progression before organ dysfunction or transformation events, despite not meeting high-tumor burden therapy indications.
The retrospective study included data from the Alberta Lymphoma Database on patients with grade 1-3a follicular lymphoma aged 18-70 years who were diagnosed between 1994 and 2011. Investigators identified 238 patients initially managed with watchful waiting, with a median age of 54.1 years at diagnosis. More than 80% were advanced stage.
Only 71% of these patients progressed, with a median time to progression of about 30 months and a 10-year survival rate from diagnosis of 81.2%, investigators said. However, 58 patients (24.4%) had organ dysfunction or transformation at the time of progression.
Those adverse outcomes significantly affected overall survival. The 10-year overall survival was 65.4% for patients with transformation at progression versus 83.2% for those without (P = .0017). Likewise, 10-year overall survival was 71.5% and 82.7%, respectively, for those with organ dysfunction at progression and those without (P = .028).
Investigators also looked at a comparison group of 236 follicular lymphoma patients managed with immediate rituximab chemotherapy. They found survival outcomes in that group were similar to those in the subgroup of 56 watchful waiting patients who received primarily rituximab-containing regimens at the time of organ dysfunction or transformation.
Taken together, the findings suggest management changes may be warranted for follicular lymphoma patients managed according to a watchful waiting strategy, the investigators wrote. “Consideration should be given to implementing standardized follow-up imaging, with early initiation of rituximab-based therapy if there is evidence of progression in an attempt to prevent these potentially clinically impactful events.”
Dr. Davies reported having no financial disclosures. Study coauthors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.
SOURCE: Davies GA et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 28. doi: 10.1016/j.clml.2018.08.015.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA
Key clinical point:
Major finding: A total of 58 patients (24.4%) had organ dysfunction or transformation at the time of progression and had worse survival outcomes, compared with patients who did not experience those events.
Study details: A retrospective study including data on 238 patients with grade 1-3a follicular lymphoma aged 18-70 years who were managed with watchful waiting.
Disclosures: Study authors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.
Source: Davies GA et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 28. doi: 10.1016/j.clml.2018.08.015.
Pruritus linked to wide variety of cancers
A wide variety of hematologic, dermatologic, and solid organ malignancies are associated with pruritus, a large, single-center, retrospective study suggests.
Blacks with pruritus had a higher odds ratio of hematologic malignancies, among others, while whites had higher likelihood of liver, gastrointestinal, respiratory and gynecologic cancers, results of the study show.
The results by race help address a gap in the literature, according to Shawn G. Kwatra, MD, of Johns Hopkins University, Baltimore, and his coinvestigators.
“Little is known about the association between pruritus and malignancy among different ethnic groups,” Dr. Kwatra and his coauthors wrote in the Journal of the American Academy of Dermatology.
The study shows a stronger association with more types of malignancies than has been reported previously, according to the investigators.
“The main difference is that prior studies focused on diagnosis of malignancy after the onset of pruritus, while our study includes malignancies diagnosed on or after pruritus onset,” they wrote.
Retrospective data for the study, which came from the Johns Hopkins Health System, included 16,925 patients aged 18 years or older who presented with itching or pruritus between April 4, 2013 and Dec. 31, 2017.
Of those 16,925 patients, 2,903 were also diagnosed with a concomitant malignancy during that time period. Compared with patients with no itching diagnosis during that time period, the pruritus patients more likely to have a concomitant malignancy, with an OR of 5.76 (95% confidence interval, 5.53-6.00), Dr. Kwatra and his colleagues found.
Malignancies most strongly associated with pruritus included those of the skin, liver, gallbladder and biliary tract, and hematopoietic system.
Among hematologic malignancies, pruritus was most strongly linked to myeloid leukemia and primary cutaneous lymphoma, while among skin cancers, squamous cell carcinoma was most strongly linked.
Whites had higher odds of any malignancy versus blacks, according to investigators, with ORs of 6.12 (95% CI, 5.81-6.46) and 5.61 (95% CI, 5.21-6.04), respectively.
Blacks with pruritus had higher ORs for hematologic and soft tissue malignancies including those of the muscle, fat, and peripheral nerve, investigators said, while whites had higher ORs for skin and liver malignancies.
The investigators also looked at the prevalence of skin eruptions in patients with pruritus and malignancy. “Eruption is variable by malignancy type and points to differing underlying mechanisms of pruritus,” they reported.
The highest rates of skin eruption were in patients with myeloid leukemia at 66%, followed by bone cancers at 58%, lymphocytic leukemia at 57%, multiple myeloma at 53%, and bronchus at 53%. The lowest rates of skin eruption were in patients with gallbladder and biliary tract, colon, pancreas, and liver malignancies.
Dr. Kwatra reported that he is an advisory board member for Menlo Therapeutics and Trevi Therapeutics.
SOURCE: Kwatra SG et al. J Am Acad Dermatol. 2018 Sep 11. doi: 10.1016/j.jaad.2018.08.044.
A wide variety of hematologic, dermatologic, and solid organ malignancies are associated with pruritus, a large, single-center, retrospective study suggests.
Blacks with pruritus had a higher odds ratio of hematologic malignancies, among others, while whites had higher likelihood of liver, gastrointestinal, respiratory and gynecologic cancers, results of the study show.
The results by race help address a gap in the literature, according to Shawn G. Kwatra, MD, of Johns Hopkins University, Baltimore, and his coinvestigators.
“Little is known about the association between pruritus and malignancy among different ethnic groups,” Dr. Kwatra and his coauthors wrote in the Journal of the American Academy of Dermatology.
The study shows a stronger association with more types of malignancies than has been reported previously, according to the investigators.
“The main difference is that prior studies focused on diagnosis of malignancy after the onset of pruritus, while our study includes malignancies diagnosed on or after pruritus onset,” they wrote.
Retrospective data for the study, which came from the Johns Hopkins Health System, included 16,925 patients aged 18 years or older who presented with itching or pruritus between April 4, 2013 and Dec. 31, 2017.
Of those 16,925 patients, 2,903 were also diagnosed with a concomitant malignancy during that time period. Compared with patients with no itching diagnosis during that time period, the pruritus patients more likely to have a concomitant malignancy, with an OR of 5.76 (95% confidence interval, 5.53-6.00), Dr. Kwatra and his colleagues found.
Malignancies most strongly associated with pruritus included those of the skin, liver, gallbladder and biliary tract, and hematopoietic system.
Among hematologic malignancies, pruritus was most strongly linked to myeloid leukemia and primary cutaneous lymphoma, while among skin cancers, squamous cell carcinoma was most strongly linked.
Whites had higher odds of any malignancy versus blacks, according to investigators, with ORs of 6.12 (95% CI, 5.81-6.46) and 5.61 (95% CI, 5.21-6.04), respectively.
Blacks with pruritus had higher ORs for hematologic and soft tissue malignancies including those of the muscle, fat, and peripheral nerve, investigators said, while whites had higher ORs for skin and liver malignancies.
The investigators also looked at the prevalence of skin eruptions in patients with pruritus and malignancy. “Eruption is variable by malignancy type and points to differing underlying mechanisms of pruritus,” they reported.
The highest rates of skin eruption were in patients with myeloid leukemia at 66%, followed by bone cancers at 58%, lymphocytic leukemia at 57%, multiple myeloma at 53%, and bronchus at 53%. The lowest rates of skin eruption were in patients with gallbladder and biliary tract, colon, pancreas, and liver malignancies.
Dr. Kwatra reported that he is an advisory board member for Menlo Therapeutics and Trevi Therapeutics.
SOURCE: Kwatra SG et al. J Am Acad Dermatol. 2018 Sep 11. doi: 10.1016/j.jaad.2018.08.044.
A wide variety of hematologic, dermatologic, and solid organ malignancies are associated with pruritus, a large, single-center, retrospective study suggests.
Blacks with pruritus had a higher odds ratio of hematologic malignancies, among others, while whites had higher likelihood of liver, gastrointestinal, respiratory and gynecologic cancers, results of the study show.
The results by race help address a gap in the literature, according to Shawn G. Kwatra, MD, of Johns Hopkins University, Baltimore, and his coinvestigators.
“Little is known about the association between pruritus and malignancy among different ethnic groups,” Dr. Kwatra and his coauthors wrote in the Journal of the American Academy of Dermatology.
The study shows a stronger association with more types of malignancies than has been reported previously, according to the investigators.
“The main difference is that prior studies focused on diagnosis of malignancy after the onset of pruritus, while our study includes malignancies diagnosed on or after pruritus onset,” they wrote.
Retrospective data for the study, which came from the Johns Hopkins Health System, included 16,925 patients aged 18 years or older who presented with itching or pruritus between April 4, 2013 and Dec. 31, 2017.
Of those 16,925 patients, 2,903 were also diagnosed with a concomitant malignancy during that time period. Compared with patients with no itching diagnosis during that time period, the pruritus patients more likely to have a concomitant malignancy, with an OR of 5.76 (95% confidence interval, 5.53-6.00), Dr. Kwatra and his colleagues found.
Malignancies most strongly associated with pruritus included those of the skin, liver, gallbladder and biliary tract, and hematopoietic system.
Among hematologic malignancies, pruritus was most strongly linked to myeloid leukemia and primary cutaneous lymphoma, while among skin cancers, squamous cell carcinoma was most strongly linked.
Whites had higher odds of any malignancy versus blacks, according to investigators, with ORs of 6.12 (95% CI, 5.81-6.46) and 5.61 (95% CI, 5.21-6.04), respectively.
Blacks with pruritus had higher ORs for hematologic and soft tissue malignancies including those of the muscle, fat, and peripheral nerve, investigators said, while whites had higher ORs for skin and liver malignancies.
The investigators also looked at the prevalence of skin eruptions in patients with pruritus and malignancy. “Eruption is variable by malignancy type and points to differing underlying mechanisms of pruritus,” they reported.
The highest rates of skin eruption were in patients with myeloid leukemia at 66%, followed by bone cancers at 58%, lymphocytic leukemia at 57%, multiple myeloma at 53%, and bronchus at 53%. The lowest rates of skin eruption were in patients with gallbladder and biliary tract, colon, pancreas, and liver malignancies.
Dr. Kwatra reported that he is an advisory board member for Menlo Therapeutics and Trevi Therapeutics.
SOURCE: Kwatra SG et al. J Am Acad Dermatol. 2018 Sep 11. doi: 10.1016/j.jaad.2018.08.044.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Key clinical point:
Major finding: Blacks with pruritus had higher odds ratios for hematologic and soft tissue malignancies, while whites had higher ORs for skin and liver malignancies.
Study details: A retrospective study of 16,925 adults with itching or pruritus seen at a tertiary care center.
Disclosures: Dr. Kwatra reported serving as an advisory board member for Menlo Therapeutics and Trevi Therapeutics.
Source: Kwatra SG et al. J Am Acad Dermatol. 2018 Sep 11. doi: 10.1016/j.jaad.2018.08.044.
Venetoclax label now includes MRD data
The Food and Drug Administration has expanded the label for venetoclax tablets (Venclexta) to include data on minimal residual disease.
The drug’s prescribing information will now include details on minimal residual disease (MRD) negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.
The combination of venetoclax and rituximab was approved by the FDA in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.
The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL. They were randomized to receive venetoclax plus rituximab or bendamustine plus rituximab (N Engl J Med. 2018; 378:1107-20).
Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction; the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.
The researchers assessed MRD in the peripheral blood after about 9 months on therapy (3 months after the last dose of rituximab). At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.
The researchers also assessed MRD in the peripheral blood of patients with a complete response or complete response with incomplete marrow recovery. MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.
Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States.
The Food and Drug Administration has expanded the label for venetoclax tablets (Venclexta) to include data on minimal residual disease.
The drug’s prescribing information will now include details on minimal residual disease (MRD) negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.
The combination of venetoclax and rituximab was approved by the FDA in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.
The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL. They were randomized to receive venetoclax plus rituximab or bendamustine plus rituximab (N Engl J Med. 2018; 378:1107-20).
Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction; the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.
The researchers assessed MRD in the peripheral blood after about 9 months on therapy (3 months after the last dose of rituximab). At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.
The researchers also assessed MRD in the peripheral blood of patients with a complete response or complete response with incomplete marrow recovery. MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.
Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States.
The Food and Drug Administration has expanded the label for venetoclax tablets (Venclexta) to include data on minimal residual disease.
The drug’s prescribing information will now include details on minimal residual disease (MRD) negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.
The combination of venetoclax and rituximab was approved by the FDA in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.
The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL. They were randomized to receive venetoclax plus rituximab or bendamustine plus rituximab (N Engl J Med. 2018; 378:1107-20).
Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction; the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.
The researchers assessed MRD in the peripheral blood after about 9 months on therapy (3 months after the last dose of rituximab). At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.
The researchers also assessed MRD in the peripheral blood of patients with a complete response or complete response with incomplete marrow recovery. MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.
Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States.
TP53 mutation plus complex karyotype equals poor prognosis
The presence of both TP53 gene mutation and complex karyotype may signal a dismal prognosis in patients with mantle cell lymphoma (MCL), according to results of a study.
All patients who had TP53 mutations and complex karyotype died within 1.2 years of diagnosis, while almost all patients with neither predictor were still alive at 2 years, according to study data reported in the journal Clinical Lymphoma, Myeloma & Leukemia.
By combining the markers, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment regimen, reported the study’s corresponding author Vít Procházka, MD, PhD, of the department of hemato-oncology faculty of medicine and dentistry at Palacký University, Olomouc, Czech Republic, and his coauthors.
“Our findings support a need to perform both tests, molecular cytogenetics, and next-generation sequencing simultaneously before initiation of treatment for MCL,” Dr. Procházka and his coauthors wrote.
In current clinical practice, TP53 mutational status and molecular cytogenetics are not routinely assessed prior to treatment initiation, they noted in their report.
The study, believed to be the first to evaluate the combined prognostic role of TP53 mutation and complex karyotype in an MCL cohort, included 74 consecutive adult patients newly diagnosed with MCL during 2000-2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or complex karyotype, was under observation without therapy.
Complex karyotype was found in 13 patients for whom fixed cells were available to perform cytogenetic analysis, the authors reported, while TP53 mutations were seen in 15 patients who were evaluated for that marker.
Altogether, 48 patients (64.9%) had biological material available to perform both analyses. Of those, 4 patients were found to have both TP53 mutation and complex karyotype, 12 had one of those two markers, and 32 had neither.
While patients with both markers all died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker; those differences were significant between groups (P less than .001), according to investigators.
Progression-free survival analyses showed similar results, with significant differences between the three groups, investigators reported.
Multivariate analysis showed that both TP53 mutation and complex karyotype were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index (MIPI).
While larger studies are needed to confirm the results, investigators suggested that novel treatment approaches might be warranted for patients in the highest-risk subgroup.
“The patients harboring the negative prognostic markers [TP53 mutation] and [complex karyotype] might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” they said.
The study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.
SOURCE: Obr A et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 23. doi: 10.1016/j.clml.2018.07.282.
The presence of both TP53 gene mutation and complex karyotype may signal a dismal prognosis in patients with mantle cell lymphoma (MCL), according to results of a study.
All patients who had TP53 mutations and complex karyotype died within 1.2 years of diagnosis, while almost all patients with neither predictor were still alive at 2 years, according to study data reported in the journal Clinical Lymphoma, Myeloma & Leukemia.
By combining the markers, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment regimen, reported the study’s corresponding author Vít Procházka, MD, PhD, of the department of hemato-oncology faculty of medicine and dentistry at Palacký University, Olomouc, Czech Republic, and his coauthors.
“Our findings support a need to perform both tests, molecular cytogenetics, and next-generation sequencing simultaneously before initiation of treatment for MCL,” Dr. Procházka and his coauthors wrote.
In current clinical practice, TP53 mutational status and molecular cytogenetics are not routinely assessed prior to treatment initiation, they noted in their report.
The study, believed to be the first to evaluate the combined prognostic role of TP53 mutation and complex karyotype in an MCL cohort, included 74 consecutive adult patients newly diagnosed with MCL during 2000-2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or complex karyotype, was under observation without therapy.
Complex karyotype was found in 13 patients for whom fixed cells were available to perform cytogenetic analysis, the authors reported, while TP53 mutations were seen in 15 patients who were evaluated for that marker.
Altogether, 48 patients (64.9%) had biological material available to perform both analyses. Of those, 4 patients were found to have both TP53 mutation and complex karyotype, 12 had one of those two markers, and 32 had neither.
While patients with both markers all died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker; those differences were significant between groups (P less than .001), according to investigators.
Progression-free survival analyses showed similar results, with significant differences between the three groups, investigators reported.
Multivariate analysis showed that both TP53 mutation and complex karyotype were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index (MIPI).
While larger studies are needed to confirm the results, investigators suggested that novel treatment approaches might be warranted for patients in the highest-risk subgroup.
“The patients harboring the negative prognostic markers [TP53 mutation] and [complex karyotype] might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” they said.
The study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.
SOURCE: Obr A et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 23. doi: 10.1016/j.clml.2018.07.282.
The presence of both TP53 gene mutation and complex karyotype may signal a dismal prognosis in patients with mantle cell lymphoma (MCL), according to results of a study.
All patients who had TP53 mutations and complex karyotype died within 1.2 years of diagnosis, while almost all patients with neither predictor were still alive at 2 years, according to study data reported in the journal Clinical Lymphoma, Myeloma & Leukemia.
By combining the markers, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment regimen, reported the study’s corresponding author Vít Procházka, MD, PhD, of the department of hemato-oncology faculty of medicine and dentistry at Palacký University, Olomouc, Czech Republic, and his coauthors.
“Our findings support a need to perform both tests, molecular cytogenetics, and next-generation sequencing simultaneously before initiation of treatment for MCL,” Dr. Procházka and his coauthors wrote.
In current clinical practice, TP53 mutational status and molecular cytogenetics are not routinely assessed prior to treatment initiation, they noted in their report.
The study, believed to be the first to evaluate the combined prognostic role of TP53 mutation and complex karyotype in an MCL cohort, included 74 consecutive adult patients newly diagnosed with MCL during 2000-2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or complex karyotype, was under observation without therapy.
Complex karyotype was found in 13 patients for whom fixed cells were available to perform cytogenetic analysis, the authors reported, while TP53 mutations were seen in 15 patients who were evaluated for that marker.
Altogether, 48 patients (64.9%) had biological material available to perform both analyses. Of those, 4 patients were found to have both TP53 mutation and complex karyotype, 12 had one of those two markers, and 32 had neither.
While patients with both markers all died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker; those differences were significant between groups (P less than .001), according to investigators.
Progression-free survival analyses showed similar results, with significant differences between the three groups, investigators reported.
Multivariate analysis showed that both TP53 mutation and complex karyotype were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index (MIPI).
While larger studies are needed to confirm the results, investigators suggested that novel treatment approaches might be warranted for patients in the highest-risk subgroup.
“The patients harboring the negative prognostic markers [TP53 mutation] and [complex karyotype] might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” they said.
The study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.
SOURCE: Obr A et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 23. doi: 10.1016/j.clml.2018.07.282.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA
Key clinical point:
Major finding: Patients with both markers all died within 1.2 years, while 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker (P less than .001).
Study details: A study of 74 consecutive adult patients newly diagnosed with MCL during 2000-2014.
Disclosures: The study was supported by grants from the Czech Ministry of Health and Palacký University, Olomouc, Czech Republic. Study authors reported having no conflicts of interest.
Source: Obr A et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 23. doi: 10.1016/j.clml.2018.07.282.
ASCO updates guidance on prophylaxis for adults with cancer-related immunosuppression
Fluoroquinolones are recommended for adults with cancer-related immunosuppression if they are at high risk of infection, according to an updated clinical practice guideline on antimicrobial prophylaxis.
By contrast, patients with solid tumors are not routinely recommended to receive antibiotic prophylaxis, according to the guideline, developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA).
The guideline includes antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions such as hand hygiene that may reduce infection risk.
Released in the Journal of Clinical Oncology, the updated guidelines were developed by an expert panel cochaired by Christopher R. Flowers, MD of Emory University, Atlanta, and Randy A. Taplitz, MD of the University of California, San Diego, Health.
For the most part, the panel endorsed the previous ASCO recommendations, published in 2013. However, the panel considered six new high-quality studies and six new or updated meta-analyses to make modifications and add some new recommendations.
Fluoroquinolones, in the 2013 guideline, were recommended over trimethoprim-sulfamethoxazole because of fewer adverse events leading to treatment discontinuation. Panelists for the new guidelines said they continued to support that recommendation, based on an updated literature review.
That review showed significant reductions in both febrile neutropenia incidence and all-cause mortality, not only for patients at high risk of febrile neutropenia or profound, protracted neutropenia but also for lower-risk patients with solid tumors, they said.
However, the benefits did not sufficiently outweigh the harms to justify recommending fluoroquinolone prophylaxis for all patients with solid tumors or lymphoma, according to the report from the expert panel.
Those harms could include antibiotic-associated adverse effects, emergence of resistance, and Clostridium difficile infections, they said.
Accordingly, they recommended fluoroquinolone prophylaxis for the high-risk patients, including most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) or those undergoing hematopoietic stem-cell transplantation (HSCT).
Similarly, the panel recommended that high-risk patients should receive antifungal prophylaxis with an oral triazole or parenteral echinocandin, while prophylaxis would not be routinely recommended for solid tumor patients.
By contrast, all patients undergoing chemotherapy for malignancy should receive yearly influenza vaccination with an inactivated quadrivalent vaccine, the panel said in its antiviral prophylaxis recommendations.
Family members, household contacts, and health care providers also should receive influenza vaccinations, said the panel, endorsing recommendations from the Centers for Disease Control and Prevention that were also cited in the 2013 ASCO guidelines.
Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce risk of pathogen transmission, the panel said, endorsing CDC recommendations cited in the previous guideline.
However, the panel said they recommend against interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks.
“Evidence of clinical benefit is lacking” for those interventions, they said.
Participants in the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.
SOURCE: Taplitz RA et al. J Clin Oncol. 2018 Sept 4. doi: 10.1200/JCO.18.00374.
Fluoroquinolones are recommended for adults with cancer-related immunosuppression if they are at high risk of infection, according to an updated clinical practice guideline on antimicrobial prophylaxis.
By contrast, patients with solid tumors are not routinely recommended to receive antibiotic prophylaxis, according to the guideline, developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA).
The guideline includes antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions such as hand hygiene that may reduce infection risk.
Released in the Journal of Clinical Oncology, the updated guidelines were developed by an expert panel cochaired by Christopher R. Flowers, MD of Emory University, Atlanta, and Randy A. Taplitz, MD of the University of California, San Diego, Health.
For the most part, the panel endorsed the previous ASCO recommendations, published in 2013. However, the panel considered six new high-quality studies and six new or updated meta-analyses to make modifications and add some new recommendations.
Fluoroquinolones, in the 2013 guideline, were recommended over trimethoprim-sulfamethoxazole because of fewer adverse events leading to treatment discontinuation. Panelists for the new guidelines said they continued to support that recommendation, based on an updated literature review.
That review showed significant reductions in both febrile neutropenia incidence and all-cause mortality, not only for patients at high risk of febrile neutropenia or profound, protracted neutropenia but also for lower-risk patients with solid tumors, they said.
However, the benefits did not sufficiently outweigh the harms to justify recommending fluoroquinolone prophylaxis for all patients with solid tumors or lymphoma, according to the report from the expert panel.
Those harms could include antibiotic-associated adverse effects, emergence of resistance, and Clostridium difficile infections, they said.
Accordingly, they recommended fluoroquinolone prophylaxis for the high-risk patients, including most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) or those undergoing hematopoietic stem-cell transplantation (HSCT).
Similarly, the panel recommended that high-risk patients should receive antifungal prophylaxis with an oral triazole or parenteral echinocandin, while prophylaxis would not be routinely recommended for solid tumor patients.
By contrast, all patients undergoing chemotherapy for malignancy should receive yearly influenza vaccination with an inactivated quadrivalent vaccine, the panel said in its antiviral prophylaxis recommendations.
Family members, household contacts, and health care providers also should receive influenza vaccinations, said the panel, endorsing recommendations from the Centers for Disease Control and Prevention that were also cited in the 2013 ASCO guidelines.
Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce risk of pathogen transmission, the panel said, endorsing CDC recommendations cited in the previous guideline.
However, the panel said they recommend against interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks.
“Evidence of clinical benefit is lacking” for those interventions, they said.
Participants in the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.
SOURCE: Taplitz RA et al. J Clin Oncol. 2018 Sept 4. doi: 10.1200/JCO.18.00374.
Fluoroquinolones are recommended for adults with cancer-related immunosuppression if they are at high risk of infection, according to an updated clinical practice guideline on antimicrobial prophylaxis.
By contrast, patients with solid tumors are not routinely recommended to receive antibiotic prophylaxis, according to the guideline, developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA).
The guideline includes antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions such as hand hygiene that may reduce infection risk.
Released in the Journal of Clinical Oncology, the updated guidelines were developed by an expert panel cochaired by Christopher R. Flowers, MD of Emory University, Atlanta, and Randy A. Taplitz, MD of the University of California, San Diego, Health.
For the most part, the panel endorsed the previous ASCO recommendations, published in 2013. However, the panel considered six new high-quality studies and six new or updated meta-analyses to make modifications and add some new recommendations.
Fluoroquinolones, in the 2013 guideline, were recommended over trimethoprim-sulfamethoxazole because of fewer adverse events leading to treatment discontinuation. Panelists for the new guidelines said they continued to support that recommendation, based on an updated literature review.
That review showed significant reductions in both febrile neutropenia incidence and all-cause mortality, not only for patients at high risk of febrile neutropenia or profound, protracted neutropenia but also for lower-risk patients with solid tumors, they said.
However, the benefits did not sufficiently outweigh the harms to justify recommending fluoroquinolone prophylaxis for all patients with solid tumors or lymphoma, according to the report from the expert panel.
Those harms could include antibiotic-associated adverse effects, emergence of resistance, and Clostridium difficile infections, they said.
Accordingly, they recommended fluoroquinolone prophylaxis for the high-risk patients, including most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) or those undergoing hematopoietic stem-cell transplantation (HSCT).
Similarly, the panel recommended that high-risk patients should receive antifungal prophylaxis with an oral triazole or parenteral echinocandin, while prophylaxis would not be routinely recommended for solid tumor patients.
By contrast, all patients undergoing chemotherapy for malignancy should receive yearly influenza vaccination with an inactivated quadrivalent vaccine, the panel said in its antiviral prophylaxis recommendations.
Family members, household contacts, and health care providers also should receive influenza vaccinations, said the panel, endorsing recommendations from the Centers for Disease Control and Prevention that were also cited in the 2013 ASCO guidelines.
Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce risk of pathogen transmission, the panel said, endorsing CDC recommendations cited in the previous guideline.
However, the panel said they recommend against interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks.
“Evidence of clinical benefit is lacking” for those interventions, they said.
Participants in the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.
SOURCE: Taplitz RA et al. J Clin Oncol. 2018 Sept 4. doi: 10.1200/JCO.18.00374.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Novartis nabs first CAR T approval in Canada
the first chimeric antigen receptor (CAR) T-cell therapy to receive regulatory approval in Canada.
Tisagenlecleucel is approved to treat patients aged 3-25 years who have B-cell acute lymphoblastic leukemia (ALL) and relapsed after allogenic stem cell transplant (SCT) or are otherwise ineligible for SCT, have experienced second or later relapse, or have refractory disease.
Tisagenlecleucel is also approved in Canada to treat adults who have received two or more lines of systemic therapy and have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.
Novartis, the company marketing tisagenlecleucel, said it is working with qualified treatment centers in Canada to prepare for the delivery of tisagenlecleucel. Certification and training are underway at these centers and Novartis is enhancing manufacturing capacity to meet patient needs.
Tisagenlecleucel has been studied in a pair of phase 2 trials – JULIET and ELIANA.
JULIET enrolled 165 adults with relapsed/refractory DLBCL, 111 of whom received a single infusion of tisagenlecleucel.
The overall response rate was 52% and the complete response (CR) rate was 40%. The median duration of response was not reached with a median follow-up of 13.9 months. At last follow-up, none of the responders had gone on to SCT.
The 12-month overall survival (OS) rate was 49%; the median OS was 11.7 months. The median OS was not reached for patients in CR.
Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome.
These results were presented at the 2018 annual congress of the European Hematology Association in June.
The ELIANA trial included 75 children and young adults with relapsed/refractory ALL. All patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.
The median duration of follow-up was 13.1 months. The overall remission rate was 81%, with 60% of patients achieving a CR and 21% achieving CR with incomplete hematologic recovery. All patients whose best response was CR with incomplete hematologic recovery were negative for minimal residual disease. The median duration of response was not met.
Eight patients proceeded to SCT while in remission. At last follow-up, four were still in remission, and four had unknown disease status.
At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.
About 95% of patients had adverse events thought to be related to tisagenlecleucel. The incidence of treatment-related grade 3/4 adverse eventss was 73% (N Engl J Med 2018; 378:439-48).
the first chimeric antigen receptor (CAR) T-cell therapy to receive regulatory approval in Canada.
Tisagenlecleucel is approved to treat patients aged 3-25 years who have B-cell acute lymphoblastic leukemia (ALL) and relapsed after allogenic stem cell transplant (SCT) or are otherwise ineligible for SCT, have experienced second or later relapse, or have refractory disease.
Tisagenlecleucel is also approved in Canada to treat adults who have received two or more lines of systemic therapy and have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.
Novartis, the company marketing tisagenlecleucel, said it is working with qualified treatment centers in Canada to prepare for the delivery of tisagenlecleucel. Certification and training are underway at these centers and Novartis is enhancing manufacturing capacity to meet patient needs.
Tisagenlecleucel has been studied in a pair of phase 2 trials – JULIET and ELIANA.
JULIET enrolled 165 adults with relapsed/refractory DLBCL, 111 of whom received a single infusion of tisagenlecleucel.
The overall response rate was 52% and the complete response (CR) rate was 40%. The median duration of response was not reached with a median follow-up of 13.9 months. At last follow-up, none of the responders had gone on to SCT.
The 12-month overall survival (OS) rate was 49%; the median OS was 11.7 months. The median OS was not reached for patients in CR.
Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome.
These results were presented at the 2018 annual congress of the European Hematology Association in June.
The ELIANA trial included 75 children and young adults with relapsed/refractory ALL. All patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.
The median duration of follow-up was 13.1 months. The overall remission rate was 81%, with 60% of patients achieving a CR and 21% achieving CR with incomplete hematologic recovery. All patients whose best response was CR with incomplete hematologic recovery were negative for minimal residual disease. The median duration of response was not met.
Eight patients proceeded to SCT while in remission. At last follow-up, four were still in remission, and four had unknown disease status.
At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.
About 95% of patients had adverse events thought to be related to tisagenlecleucel. The incidence of treatment-related grade 3/4 adverse eventss was 73% (N Engl J Med 2018; 378:439-48).
the first chimeric antigen receptor (CAR) T-cell therapy to receive regulatory approval in Canada.
Tisagenlecleucel is approved to treat patients aged 3-25 years who have B-cell acute lymphoblastic leukemia (ALL) and relapsed after allogenic stem cell transplant (SCT) or are otherwise ineligible for SCT, have experienced second or later relapse, or have refractory disease.
Tisagenlecleucel is also approved in Canada to treat adults who have received two or more lines of systemic therapy and have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.
Novartis, the company marketing tisagenlecleucel, said it is working with qualified treatment centers in Canada to prepare for the delivery of tisagenlecleucel. Certification and training are underway at these centers and Novartis is enhancing manufacturing capacity to meet patient needs.
Tisagenlecleucel has been studied in a pair of phase 2 trials – JULIET and ELIANA.
JULIET enrolled 165 adults with relapsed/refractory DLBCL, 111 of whom received a single infusion of tisagenlecleucel.
The overall response rate was 52% and the complete response (CR) rate was 40%. The median duration of response was not reached with a median follow-up of 13.9 months. At last follow-up, none of the responders had gone on to SCT.
The 12-month overall survival (OS) rate was 49%; the median OS was 11.7 months. The median OS was not reached for patients in CR.
Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome.
These results were presented at the 2018 annual congress of the European Hematology Association in June.
The ELIANA trial included 75 children and young adults with relapsed/refractory ALL. All patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.
The median duration of follow-up was 13.1 months. The overall remission rate was 81%, with 60% of patients achieving a CR and 21% achieving CR with incomplete hematologic recovery. All patients whose best response was CR with incomplete hematologic recovery were negative for minimal residual disease. The median duration of response was not met.
Eight patients proceeded to SCT while in remission. At last follow-up, four were still in remission, and four had unknown disease status.
At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.
About 95% of patients had adverse events thought to be related to tisagenlecleucel. The incidence of treatment-related grade 3/4 adverse eventss was 73% (N Engl J Med 2018; 378:439-48).
RESONATE-2 update: First-line ibrutinib has sustained efficacy in older CLL patients
In older patients with chronic lymphocytic leukemia (CLL), first-line treatment with ibrutinib resulted in a long-term progression-free survival benefit versus chemotherapy, according to extended follow-up results of a phase 3 trial.
The quality of response to ibrutinib continued to improve over time in the study, including a substantial increase in the proportion of patients achieving complete response, the updated results of the RESONATE-2 trial show.
Rates of serious adverse events decreased over time in the study, while common reasons for initiating treatment, such as marrow failure and disease symptoms, all improved to a greater extent than with chlorambucil, reported Paul M. Barr, MD, of the University of Rochester (N.Y.) and colleagues.
“These data support the use of ibrutinib in the first-line treatment of CLL as a chemotherapy-free option that can be taken continuously, achieving long-term disease control for the majority of patients, including those with high-risk features,” Dr. Barr and coauthors said in the journal Haematologica.
Previously reported primary results of the RESONATE-2 trial, which showed an 84% reduction in risk of death for ibrutinib versus chlorambucil with a median follow-up of 18 months, led to the approval of ibrutinib for first-line CLL treatment, the authors said.
The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized 1:1 to ibrutinib or chlorambucil.
Out of 136 ibrutinib-treated patients, 107 (79%) remained on therapy at this extended analysis, which had a median follow-up of 29 months.
The extended analysis also showed an 88% reduction in risk of progression or death for those patients randomized to ibrutinib (P less than .0001), with significant improvements in subgroups evaluated, which include groups typically considered high risk, according to Dr. Barr and colleagues.
The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months, to 15% at 24 months, and to 18% with a maximum of 36 months’ follow-up, they said.
The overall response rate for ibrutinib was 92% in this extended analysis, with comparable findings in high-risk subgroups, including those with del(11q) at 100% and unmutated IGHV at 95%, according to the report.
Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42% versus 7% with chlorambucil. Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients versus 52% for chlorambucil, with complete resolution in 56% of ibrutinib-treated patients and 22% of chlorambucil-treated patients.
Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time. Rates of grade 3 or greater neutropenia, anemia, and thrombocytopenia were 8.1%, 5.9%, and 2.2%, respectively, in the first 12 months of treatment; those decreased to 0%, 1%, and 0% in the third year.
The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up; however, investigators said ibrutinib dose reductions and discontinuations because of this adverse effect were uncommon and less frequent with extended treatment.
“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.
The study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.
SOURCE: Barr PM, et al. Haematologica. 2018;103(9):1502-10.
In older patients with chronic lymphocytic leukemia (CLL), first-line treatment with ibrutinib resulted in a long-term progression-free survival benefit versus chemotherapy, according to extended follow-up results of a phase 3 trial.
The quality of response to ibrutinib continued to improve over time in the study, including a substantial increase in the proportion of patients achieving complete response, the updated results of the RESONATE-2 trial show.
Rates of serious adverse events decreased over time in the study, while common reasons for initiating treatment, such as marrow failure and disease symptoms, all improved to a greater extent than with chlorambucil, reported Paul M. Barr, MD, of the University of Rochester (N.Y.) and colleagues.
“These data support the use of ibrutinib in the first-line treatment of CLL as a chemotherapy-free option that can be taken continuously, achieving long-term disease control for the majority of patients, including those with high-risk features,” Dr. Barr and coauthors said in the journal Haematologica.
Previously reported primary results of the RESONATE-2 trial, which showed an 84% reduction in risk of death for ibrutinib versus chlorambucil with a median follow-up of 18 months, led to the approval of ibrutinib for first-line CLL treatment, the authors said.
The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized 1:1 to ibrutinib or chlorambucil.
Out of 136 ibrutinib-treated patients, 107 (79%) remained on therapy at this extended analysis, which had a median follow-up of 29 months.
The extended analysis also showed an 88% reduction in risk of progression or death for those patients randomized to ibrutinib (P less than .0001), with significant improvements in subgroups evaluated, which include groups typically considered high risk, according to Dr. Barr and colleagues.
The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months, to 15% at 24 months, and to 18% with a maximum of 36 months’ follow-up, they said.
The overall response rate for ibrutinib was 92% in this extended analysis, with comparable findings in high-risk subgroups, including those with del(11q) at 100% and unmutated IGHV at 95%, according to the report.
Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42% versus 7% with chlorambucil. Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients versus 52% for chlorambucil, with complete resolution in 56% of ibrutinib-treated patients and 22% of chlorambucil-treated patients.
Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time. Rates of grade 3 or greater neutropenia, anemia, and thrombocytopenia were 8.1%, 5.9%, and 2.2%, respectively, in the first 12 months of treatment; those decreased to 0%, 1%, and 0% in the third year.
The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up; however, investigators said ibrutinib dose reductions and discontinuations because of this adverse effect were uncommon and less frequent with extended treatment.
“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.
The study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.
SOURCE: Barr PM, et al. Haematologica. 2018;103(9):1502-10.
In older patients with chronic lymphocytic leukemia (CLL), first-line treatment with ibrutinib resulted in a long-term progression-free survival benefit versus chemotherapy, according to extended follow-up results of a phase 3 trial.
The quality of response to ibrutinib continued to improve over time in the study, including a substantial increase in the proportion of patients achieving complete response, the updated results of the RESONATE-2 trial show.
Rates of serious adverse events decreased over time in the study, while common reasons for initiating treatment, such as marrow failure and disease symptoms, all improved to a greater extent than with chlorambucil, reported Paul M. Barr, MD, of the University of Rochester (N.Y.) and colleagues.
“These data support the use of ibrutinib in the first-line treatment of CLL as a chemotherapy-free option that can be taken continuously, achieving long-term disease control for the majority of patients, including those with high-risk features,” Dr. Barr and coauthors said in the journal Haematologica.
Previously reported primary results of the RESONATE-2 trial, which showed an 84% reduction in risk of death for ibrutinib versus chlorambucil with a median follow-up of 18 months, led to the approval of ibrutinib for first-line CLL treatment, the authors said.
The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized 1:1 to ibrutinib or chlorambucil.
Out of 136 ibrutinib-treated patients, 107 (79%) remained on therapy at this extended analysis, which had a median follow-up of 29 months.
The extended analysis also showed an 88% reduction in risk of progression or death for those patients randomized to ibrutinib (P less than .0001), with significant improvements in subgroups evaluated, which include groups typically considered high risk, according to Dr. Barr and colleagues.
The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months, to 15% at 24 months, and to 18% with a maximum of 36 months’ follow-up, they said.
The overall response rate for ibrutinib was 92% in this extended analysis, with comparable findings in high-risk subgroups, including those with del(11q) at 100% and unmutated IGHV at 95%, according to the report.
Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42% versus 7% with chlorambucil. Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients versus 52% for chlorambucil, with complete resolution in 56% of ibrutinib-treated patients and 22% of chlorambucil-treated patients.
Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time. Rates of grade 3 or greater neutropenia, anemia, and thrombocytopenia were 8.1%, 5.9%, and 2.2%, respectively, in the first 12 months of treatment; those decreased to 0%, 1%, and 0% in the third year.
The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up; however, investigators said ibrutinib dose reductions and discontinuations because of this adverse effect were uncommon and less frequent with extended treatment.
“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.
The study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.
SOURCE: Barr PM, et al. Haematologica. 2018;103(9):1502-10.
FROM HAEMATOLOGICA
Key clinical point:
Major finding: There was an 88% reduction in risk of progression-free survival events for those patients randomized to ibrutinib (P less than .0001).
Study details: Extended phase 3 results from the RESONATE-2 trial, including 269 older patients with untreated CLL or small lymphocytic lymphoma.
Disclosures: This study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data.
Source: Barr PM et al. Haematologica. 2018;103(9):1502-10.