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Four-drug combo bests triplet in newly diagnosed myeloma
CHICAGO – Daratumumab plus bortezomib, thalidomide, and dexamethasone (D-VTd) provided a “robust clinical benefit” over bortezomib, thalidomide, and dexamethasone alone (VTd) in a phase 3 trial of patients with newly diagnosed multiple myeloma, according to the trial’s principal investigator.
D-VTd produced significantly higher rates of stringent complete response (sCR) and progression-free survival (PFS) than did VTd, said Philippe Moreau, MD, of the University Hospital of Nantes (France).
Dr. Moreau presented these results, from the CASSIOPEIA trial, at the annual meeting of the American Society of Clinical Oncology. The findings were simultaneously published in the Lancet (2019 Jun 3. doi: 10.1016/S0140-6736[19]31240-1).
CASSIOPEIA enrolled 1,085 patients with newly diagnosed multiple myeloma who were eligible for high-dose chemotherapy and hematopoietic stem cell transplant (HSCT). This is a two-part trial, and Dr. Moreau presented final results from part 1.
In part 1, patients were randomized to induction with D-VTd or VTd, followed by autologous HSCT and consolidation with D-VTd or VTd. In part 2, which is ongoing, patients who achieve a partial response or better are randomized to observation or maintenance with daratumumab for up to 2 years.
Baseline characteristics were well balanced between the D-VTd and VTd arms. The median age was 59 years (range, 22-65) and 58 years (range, 26-65), respectively. Most patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and most had an International Staging System stage of I or II.
The median follow-up was 18.8 months. Most patients completed induction – 85% in the D-VTd arm and 81% in the VTd arm – and went on to HSCT – 90% and 89%, respectively. The most common reasons for treatment discontinuation in both arms were adverse events and progression.
Response and survival
The primary endpoint for part 1 was the rate of sCR at 100 days after HSCT. The sCR rate was significantly higher in the D-VTd arm than it was in the VTd arm – 29% and 20%, respectively (odds ratio, 1.60; P less than .0010).
The overall response rate was significantly higher in the D-VTd arm than in the VTd arm – 93% and 90%, respectively (P less than .0001) – as was the rate of minimal residual disease (MRD) negativity – 64% and 44%, respectively (P less than .0001).
Dr. Moreau noted that sCR and MRD negativity rates were superior with D-VTd across all subgroups except among patients with high-risk cytogenetics and International Staging System stage III disease.
“Dara-VTd resulted in a robust clinical benefit with a higher rate of response, including stringent CR, including MRD negativity,” Dr. Moreau said. “And this translated into a better progression-free survival, with a 53% reduction in the risk of progression or death.”
The 18-month PFS was 93% in the D-VTd arm and 85% in the VTd arm (hazard ratio, 0.47; P less than .0001). D-VTd reduced the risk of progression or death across all subgroups.
The median overall survival (OS) was not reached in either treatment arm. The 18-month OS rate was 98% in the D-VTd arm and 95% in the VTd arm. The 24-month OS rate was 97% and 93%, respectively.
“These results are the best ever reported in the setting of stem cell transplantation,” Dr. Moreau said.
Safety
The most common grade 3/4 treatment-emergent adverse events (in the D-VTd and VTd arms, respectively) were neutropenia (28% and 15%), lymphopenia (17% and 10%), stomatitis (13% and 16%), and thrombocytopenia (11% and 7%).
The rate of infusion-related reactions was 35% in the D-VTd arm and 0% in the VTd arm. The rate of infections was 66% and 57%, respectively. The most common serious infection was pneumonia, which occurred in 4% and 2% of patients, respectively. The rate of second primary malignancies was 2% in both arms.
Based on the safety and efficacy results, Dr. Moreau concluded that D-VTd “should be considered a valid treatment option” for newly diagnosed multiple myeloma patients who are eligible for HSCT.
Dr. Moreau reported relationships with Amgen, Celgene, Janssen-Cilag, Novartis, and Takeda. The study is sponsored by the French Intergroupe Francophone du Myelome in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology and Janssen Research & Development.
SOURCE: Moreau P et al. ASCO 2019, Abstract 8003.
CHICAGO – Daratumumab plus bortezomib, thalidomide, and dexamethasone (D-VTd) provided a “robust clinical benefit” over bortezomib, thalidomide, and dexamethasone alone (VTd) in a phase 3 trial of patients with newly diagnosed multiple myeloma, according to the trial’s principal investigator.
D-VTd produced significantly higher rates of stringent complete response (sCR) and progression-free survival (PFS) than did VTd, said Philippe Moreau, MD, of the University Hospital of Nantes (France).
Dr. Moreau presented these results, from the CASSIOPEIA trial, at the annual meeting of the American Society of Clinical Oncology. The findings were simultaneously published in the Lancet (2019 Jun 3. doi: 10.1016/S0140-6736[19]31240-1).
CASSIOPEIA enrolled 1,085 patients with newly diagnosed multiple myeloma who were eligible for high-dose chemotherapy and hematopoietic stem cell transplant (HSCT). This is a two-part trial, and Dr. Moreau presented final results from part 1.
In part 1, patients were randomized to induction with D-VTd or VTd, followed by autologous HSCT and consolidation with D-VTd or VTd. In part 2, which is ongoing, patients who achieve a partial response or better are randomized to observation or maintenance with daratumumab for up to 2 years.
Baseline characteristics were well balanced between the D-VTd and VTd arms. The median age was 59 years (range, 22-65) and 58 years (range, 26-65), respectively. Most patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and most had an International Staging System stage of I or II.
The median follow-up was 18.8 months. Most patients completed induction – 85% in the D-VTd arm and 81% in the VTd arm – and went on to HSCT – 90% and 89%, respectively. The most common reasons for treatment discontinuation in both arms were adverse events and progression.
Response and survival
The primary endpoint for part 1 was the rate of sCR at 100 days after HSCT. The sCR rate was significantly higher in the D-VTd arm than it was in the VTd arm – 29% and 20%, respectively (odds ratio, 1.60; P less than .0010).
The overall response rate was significantly higher in the D-VTd arm than in the VTd arm – 93% and 90%, respectively (P less than .0001) – as was the rate of minimal residual disease (MRD) negativity – 64% and 44%, respectively (P less than .0001).
Dr. Moreau noted that sCR and MRD negativity rates were superior with D-VTd across all subgroups except among patients with high-risk cytogenetics and International Staging System stage III disease.
“Dara-VTd resulted in a robust clinical benefit with a higher rate of response, including stringent CR, including MRD negativity,” Dr. Moreau said. “And this translated into a better progression-free survival, with a 53% reduction in the risk of progression or death.”
The 18-month PFS was 93% in the D-VTd arm and 85% in the VTd arm (hazard ratio, 0.47; P less than .0001). D-VTd reduced the risk of progression or death across all subgroups.
The median overall survival (OS) was not reached in either treatment arm. The 18-month OS rate was 98% in the D-VTd arm and 95% in the VTd arm. The 24-month OS rate was 97% and 93%, respectively.
“These results are the best ever reported in the setting of stem cell transplantation,” Dr. Moreau said.
Safety
The most common grade 3/4 treatment-emergent adverse events (in the D-VTd and VTd arms, respectively) were neutropenia (28% and 15%), lymphopenia (17% and 10%), stomatitis (13% and 16%), and thrombocytopenia (11% and 7%).
The rate of infusion-related reactions was 35% in the D-VTd arm and 0% in the VTd arm. The rate of infections was 66% and 57%, respectively. The most common serious infection was pneumonia, which occurred in 4% and 2% of patients, respectively. The rate of second primary malignancies was 2% in both arms.
Based on the safety and efficacy results, Dr. Moreau concluded that D-VTd “should be considered a valid treatment option” for newly diagnosed multiple myeloma patients who are eligible for HSCT.
Dr. Moreau reported relationships with Amgen, Celgene, Janssen-Cilag, Novartis, and Takeda. The study is sponsored by the French Intergroupe Francophone du Myelome in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology and Janssen Research & Development.
SOURCE: Moreau P et al. ASCO 2019, Abstract 8003.
CHICAGO – Daratumumab plus bortezomib, thalidomide, and dexamethasone (D-VTd) provided a “robust clinical benefit” over bortezomib, thalidomide, and dexamethasone alone (VTd) in a phase 3 trial of patients with newly diagnosed multiple myeloma, according to the trial’s principal investigator.
D-VTd produced significantly higher rates of stringent complete response (sCR) and progression-free survival (PFS) than did VTd, said Philippe Moreau, MD, of the University Hospital of Nantes (France).
Dr. Moreau presented these results, from the CASSIOPEIA trial, at the annual meeting of the American Society of Clinical Oncology. The findings were simultaneously published in the Lancet (2019 Jun 3. doi: 10.1016/S0140-6736[19]31240-1).
CASSIOPEIA enrolled 1,085 patients with newly diagnosed multiple myeloma who were eligible for high-dose chemotherapy and hematopoietic stem cell transplant (HSCT). This is a two-part trial, and Dr. Moreau presented final results from part 1.
In part 1, patients were randomized to induction with D-VTd or VTd, followed by autologous HSCT and consolidation with D-VTd or VTd. In part 2, which is ongoing, patients who achieve a partial response or better are randomized to observation or maintenance with daratumumab for up to 2 years.
Baseline characteristics were well balanced between the D-VTd and VTd arms. The median age was 59 years (range, 22-65) and 58 years (range, 26-65), respectively. Most patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and most had an International Staging System stage of I or II.
The median follow-up was 18.8 months. Most patients completed induction – 85% in the D-VTd arm and 81% in the VTd arm – and went on to HSCT – 90% and 89%, respectively. The most common reasons for treatment discontinuation in both arms were adverse events and progression.
Response and survival
The primary endpoint for part 1 was the rate of sCR at 100 days after HSCT. The sCR rate was significantly higher in the D-VTd arm than it was in the VTd arm – 29% and 20%, respectively (odds ratio, 1.60; P less than .0010).
The overall response rate was significantly higher in the D-VTd arm than in the VTd arm – 93% and 90%, respectively (P less than .0001) – as was the rate of minimal residual disease (MRD) negativity – 64% and 44%, respectively (P less than .0001).
Dr. Moreau noted that sCR and MRD negativity rates were superior with D-VTd across all subgroups except among patients with high-risk cytogenetics and International Staging System stage III disease.
“Dara-VTd resulted in a robust clinical benefit with a higher rate of response, including stringent CR, including MRD negativity,” Dr. Moreau said. “And this translated into a better progression-free survival, with a 53% reduction in the risk of progression or death.”
The 18-month PFS was 93% in the D-VTd arm and 85% in the VTd arm (hazard ratio, 0.47; P less than .0001). D-VTd reduced the risk of progression or death across all subgroups.
The median overall survival (OS) was not reached in either treatment arm. The 18-month OS rate was 98% in the D-VTd arm and 95% in the VTd arm. The 24-month OS rate was 97% and 93%, respectively.
“These results are the best ever reported in the setting of stem cell transplantation,” Dr. Moreau said.
Safety
The most common grade 3/4 treatment-emergent adverse events (in the D-VTd and VTd arms, respectively) were neutropenia (28% and 15%), lymphopenia (17% and 10%), stomatitis (13% and 16%), and thrombocytopenia (11% and 7%).
The rate of infusion-related reactions was 35% in the D-VTd arm and 0% in the VTd arm. The rate of infections was 66% and 57%, respectively. The most common serious infection was pneumonia, which occurred in 4% and 2% of patients, respectively. The rate of second primary malignancies was 2% in both arms.
Based on the safety and efficacy results, Dr. Moreau concluded that D-VTd “should be considered a valid treatment option” for newly diagnosed multiple myeloma patients who are eligible for HSCT.
Dr. Moreau reported relationships with Amgen, Celgene, Janssen-Cilag, Novartis, and Takeda. The study is sponsored by the French Intergroupe Francophone du Myelome in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology and Janssen Research & Development.
SOURCE: Moreau P et al. ASCO 2019, Abstract 8003.
REPORTING FROM ASCO 2019
Inhibitor produces high response rate in relapsed/refractory FL
CHICAGO – The phosphoinositide 3-kinase–delta inhibitor ME-401, given with or without rituximab, produced an overall response rate of 80% in a phase 1b trial of patients with relapsed or refractory follicular lymphoma.
Response rates were similar between patients who received ME-401 alone and those who received it in combination with rituximab.
Response rates were also similar between patients on an intermittent dosing schedule and those on a continuous dosing schedule. However, intermittent dosing decreased the rate of delayed grade 3 adverse events (AEs).
“The idea that continuous inhibition of target is absolutely essential for activity of this class of drugs has not been proven,” said Andrew Zelenetz, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.
“The promising results of this somewhat novel intermittent schedule that we used with ME-401 suggests to me that we can maintain efficacy and reduce toxicity.”
Dr. Zelenetz and colleagues presented these results in a poster at the annual meeting of the American Society of Clinical Oncology.
Patients and dosing
Data were presented for 54 patients with relapsed/refractory follicular lymphoma enrolled on this study. The patients had a median age of 63.5 years, and 80% were male. They had received a median of 2 prior therapies (range, 1-10).
Initially, patients received ME-401 at 60 mg, 120 mg, or 180 mg once daily continuously on a 28-day cycle. However, the dose-escalation portion of the study was closed because response rates were comparable among the three doses, the safety profile was similar, and there were no dose-limiting toxicities.
Two additional groups of patients received ME-401 at 60 mg daily for two cycles, followed by an intermittent schedule (IS) of 60 mg on days 1-7, repeated every 28 days.
The researchers had observed delayed grade 3 AEs on the continuous schedule (CS), and they hypothesized that the IS might prevent these events. Patients could revert to the CS if they had stable disease or progressed on the IS.
“One of the advantages of this particular agent is the very long half-life,” Dr. Zelenetz said. “So, essentially, we have 2 weeks on drug and 2 weeks off [with the IS]. It takes about a week to clear the drug because it has about a 30-hour half-life.”
In all, 40 patients received ME-401 monotherapy, and 14 received ME-401 plus rituximab at 375 mg/m2 weekly for 4 weeks and then on day 1 of cycles 3-6. There were 31 patients who received ME-401 on the CS and 23 who received ME-401 on the IS.
Results
A total of 50 patients were evaluable for efficacy. The overall response rate in these patients was 80% (40/50), and 20% (10/50) achieved a complete response.
The overall response rate was 79% (30/38) in patients who received ME-401 alone, 83% (10/12) in those who received ME-401 plus rituximab, 83% (25/30) in patients on the CS, and 75% (15/20) in those on the IS.
The median duration of response and median progression-free survival have not been reached. The median follow-up for response duration is 8.8 months in the IS group and 8.3 months in the CS group. The median follow-up for progression-free survival is 5.5 months and 6.5 months, respectively.
A total of 18 patients on the IS (78%) were still on therapy at the data cutoff, as were 14 patients (45%) on the CS.
Seven patients (23%) on the CS and two patients (9%) on the IS discontinued treatment due to progression. Four patients in the IS group and two in the CS group who were switched to IS dosing reverted to CS dosing after experiencing progression.
Four CS patients (13%) discontinued treatment because of AEs, but none of the IS patients did.
AEs occurring in at least 15% of patients were diarrhea/colitis (40.7%), fatigue (35.2%), cough (33.3%), rash (24.1%), ALT increase (24.1%), nausea (24.1%), AST increase (22.2%), and decreased appetite (16.7%).
There were no grade 4-5 AEs. Grade 3 drug-related AEs of special interest (in the CS and IS groups, respectively) were diarrhea/colitis (16.1% and 8.7%), rash (12.9% and 0%), ALT increase (6.5% and 4.3%), AST increase (6.5% and 0%), pneumonia (6.5% and 0%), and mucositis (1.9% and 0%).
“[W]hile the grade 3 immune-related events seem to be very consistent in terms of class effects, they did seem to improve with transition to intermittent schedule,” said Carla Casulo, MD, of the University of Rochester (N.Y.), who reviewed this study in a poster discussion session.
“And I think that this novel design helps to create an opportunity to limit treatment and mitigate toxicity without necessarily compromising efficacy.”
The phase 1b trial is sponsored by MEI Pharma. Dr. Zelenetz reported relationships with MEI Pharma and several other companies. Dr. Casulo reported relationships with Gilead Sciences, Celgene, and Roche.
SOURCE: Zelenetz A et al. ASCO 2019, Abstract 7512.
CHICAGO – The phosphoinositide 3-kinase–delta inhibitor ME-401, given with or without rituximab, produced an overall response rate of 80% in a phase 1b trial of patients with relapsed or refractory follicular lymphoma.
Response rates were similar between patients who received ME-401 alone and those who received it in combination with rituximab.
Response rates were also similar between patients on an intermittent dosing schedule and those on a continuous dosing schedule. However, intermittent dosing decreased the rate of delayed grade 3 adverse events (AEs).
“The idea that continuous inhibition of target is absolutely essential for activity of this class of drugs has not been proven,” said Andrew Zelenetz, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.
“The promising results of this somewhat novel intermittent schedule that we used with ME-401 suggests to me that we can maintain efficacy and reduce toxicity.”
Dr. Zelenetz and colleagues presented these results in a poster at the annual meeting of the American Society of Clinical Oncology.
Patients and dosing
Data were presented for 54 patients with relapsed/refractory follicular lymphoma enrolled on this study. The patients had a median age of 63.5 years, and 80% were male. They had received a median of 2 prior therapies (range, 1-10).
Initially, patients received ME-401 at 60 mg, 120 mg, or 180 mg once daily continuously on a 28-day cycle. However, the dose-escalation portion of the study was closed because response rates were comparable among the three doses, the safety profile was similar, and there were no dose-limiting toxicities.
Two additional groups of patients received ME-401 at 60 mg daily for two cycles, followed by an intermittent schedule (IS) of 60 mg on days 1-7, repeated every 28 days.
The researchers had observed delayed grade 3 AEs on the continuous schedule (CS), and they hypothesized that the IS might prevent these events. Patients could revert to the CS if they had stable disease or progressed on the IS.
“One of the advantages of this particular agent is the very long half-life,” Dr. Zelenetz said. “So, essentially, we have 2 weeks on drug and 2 weeks off [with the IS]. It takes about a week to clear the drug because it has about a 30-hour half-life.”
In all, 40 patients received ME-401 monotherapy, and 14 received ME-401 plus rituximab at 375 mg/m2 weekly for 4 weeks and then on day 1 of cycles 3-6. There were 31 patients who received ME-401 on the CS and 23 who received ME-401 on the IS.
Results
A total of 50 patients were evaluable for efficacy. The overall response rate in these patients was 80% (40/50), and 20% (10/50) achieved a complete response.
The overall response rate was 79% (30/38) in patients who received ME-401 alone, 83% (10/12) in those who received ME-401 plus rituximab, 83% (25/30) in patients on the CS, and 75% (15/20) in those on the IS.
The median duration of response and median progression-free survival have not been reached. The median follow-up for response duration is 8.8 months in the IS group and 8.3 months in the CS group. The median follow-up for progression-free survival is 5.5 months and 6.5 months, respectively.
A total of 18 patients on the IS (78%) were still on therapy at the data cutoff, as were 14 patients (45%) on the CS.
Seven patients (23%) on the CS and two patients (9%) on the IS discontinued treatment due to progression. Four patients in the IS group and two in the CS group who were switched to IS dosing reverted to CS dosing after experiencing progression.
Four CS patients (13%) discontinued treatment because of AEs, but none of the IS patients did.
AEs occurring in at least 15% of patients were diarrhea/colitis (40.7%), fatigue (35.2%), cough (33.3%), rash (24.1%), ALT increase (24.1%), nausea (24.1%), AST increase (22.2%), and decreased appetite (16.7%).
There were no grade 4-5 AEs. Grade 3 drug-related AEs of special interest (in the CS and IS groups, respectively) were diarrhea/colitis (16.1% and 8.7%), rash (12.9% and 0%), ALT increase (6.5% and 4.3%), AST increase (6.5% and 0%), pneumonia (6.5% and 0%), and mucositis (1.9% and 0%).
“[W]hile the grade 3 immune-related events seem to be very consistent in terms of class effects, they did seem to improve with transition to intermittent schedule,” said Carla Casulo, MD, of the University of Rochester (N.Y.), who reviewed this study in a poster discussion session.
“And I think that this novel design helps to create an opportunity to limit treatment and mitigate toxicity without necessarily compromising efficacy.”
The phase 1b trial is sponsored by MEI Pharma. Dr. Zelenetz reported relationships with MEI Pharma and several other companies. Dr. Casulo reported relationships with Gilead Sciences, Celgene, and Roche.
SOURCE: Zelenetz A et al. ASCO 2019, Abstract 7512.
CHICAGO – The phosphoinositide 3-kinase–delta inhibitor ME-401, given with or without rituximab, produced an overall response rate of 80% in a phase 1b trial of patients with relapsed or refractory follicular lymphoma.
Response rates were similar between patients who received ME-401 alone and those who received it in combination with rituximab.
Response rates were also similar between patients on an intermittent dosing schedule and those on a continuous dosing schedule. However, intermittent dosing decreased the rate of delayed grade 3 adverse events (AEs).
“The idea that continuous inhibition of target is absolutely essential for activity of this class of drugs has not been proven,” said Andrew Zelenetz, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.
“The promising results of this somewhat novel intermittent schedule that we used with ME-401 suggests to me that we can maintain efficacy and reduce toxicity.”
Dr. Zelenetz and colleagues presented these results in a poster at the annual meeting of the American Society of Clinical Oncology.
Patients and dosing
Data were presented for 54 patients with relapsed/refractory follicular lymphoma enrolled on this study. The patients had a median age of 63.5 years, and 80% were male. They had received a median of 2 prior therapies (range, 1-10).
Initially, patients received ME-401 at 60 mg, 120 mg, or 180 mg once daily continuously on a 28-day cycle. However, the dose-escalation portion of the study was closed because response rates were comparable among the three doses, the safety profile was similar, and there were no dose-limiting toxicities.
Two additional groups of patients received ME-401 at 60 mg daily for two cycles, followed by an intermittent schedule (IS) of 60 mg on days 1-7, repeated every 28 days.
The researchers had observed delayed grade 3 AEs on the continuous schedule (CS), and they hypothesized that the IS might prevent these events. Patients could revert to the CS if they had stable disease or progressed on the IS.
“One of the advantages of this particular agent is the very long half-life,” Dr. Zelenetz said. “So, essentially, we have 2 weeks on drug and 2 weeks off [with the IS]. It takes about a week to clear the drug because it has about a 30-hour half-life.”
In all, 40 patients received ME-401 monotherapy, and 14 received ME-401 plus rituximab at 375 mg/m2 weekly for 4 weeks and then on day 1 of cycles 3-6. There were 31 patients who received ME-401 on the CS and 23 who received ME-401 on the IS.
Results
A total of 50 patients were evaluable for efficacy. The overall response rate in these patients was 80% (40/50), and 20% (10/50) achieved a complete response.
The overall response rate was 79% (30/38) in patients who received ME-401 alone, 83% (10/12) in those who received ME-401 plus rituximab, 83% (25/30) in patients on the CS, and 75% (15/20) in those on the IS.
The median duration of response and median progression-free survival have not been reached. The median follow-up for response duration is 8.8 months in the IS group and 8.3 months in the CS group. The median follow-up for progression-free survival is 5.5 months and 6.5 months, respectively.
A total of 18 patients on the IS (78%) were still on therapy at the data cutoff, as were 14 patients (45%) on the CS.
Seven patients (23%) on the CS and two patients (9%) on the IS discontinued treatment due to progression. Four patients in the IS group and two in the CS group who were switched to IS dosing reverted to CS dosing after experiencing progression.
Four CS patients (13%) discontinued treatment because of AEs, but none of the IS patients did.
AEs occurring in at least 15% of patients were diarrhea/colitis (40.7%), fatigue (35.2%), cough (33.3%), rash (24.1%), ALT increase (24.1%), nausea (24.1%), AST increase (22.2%), and decreased appetite (16.7%).
There were no grade 4-5 AEs. Grade 3 drug-related AEs of special interest (in the CS and IS groups, respectively) were diarrhea/colitis (16.1% and 8.7%), rash (12.9% and 0%), ALT increase (6.5% and 4.3%), AST increase (6.5% and 0%), pneumonia (6.5% and 0%), and mucositis (1.9% and 0%).
“[W]hile the grade 3 immune-related events seem to be very consistent in terms of class effects, they did seem to improve with transition to intermittent schedule,” said Carla Casulo, MD, of the University of Rochester (N.Y.), who reviewed this study in a poster discussion session.
“And I think that this novel design helps to create an opportunity to limit treatment and mitigate toxicity without necessarily compromising efficacy.”
The phase 1b trial is sponsored by MEI Pharma. Dr. Zelenetz reported relationships with MEI Pharma and several other companies. Dr. Casulo reported relationships with Gilead Sciences, Celgene, and Roche.
SOURCE: Zelenetz A et al. ASCO 2019, Abstract 7512.
REPORTING FROM ASCO 2019
FDA approves Polivy for DLBCL
The Food and Drug Administration has granted accelerated approval to Polivy (polatuzumab vedotin-piiq), in conjunction with bendamustine and a rituximab product, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have undergone at least two prior therapies.
The FDA approval is based on results of an open-label, multicenter clinical trial of 80 patients with DLBCL who had undergone at least one prior regimen. Patients received either Polivy plus bendamustine and rituximab or only bendamustine and rituximab for six 21-day cycles. At the completion of therapy, 40% of patients who received Polivy in conjunction with bendamustine and rituximab achieved a complete response, compared with 18% of patients who received only bendamustine and rituximab; total response was 63% in those who received Polivy and 25% in those who did not.
The most common adverse events included neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia. Serious adverse events occurred in 64% of patients, most commonly from infection; the most common cause for treatment discontinuation was cytopenia.
The recommended dose of Polivy is 1.8 mg/kg as an intravenous infusion over 90 minutes every 21 days for six cycles in combination with bendamustine and a rituximab product, the FDA said. Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated.
Find the full press release on the FDA website.
The Food and Drug Administration has granted accelerated approval to Polivy (polatuzumab vedotin-piiq), in conjunction with bendamustine and a rituximab product, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have undergone at least two prior therapies.
The FDA approval is based on results of an open-label, multicenter clinical trial of 80 patients with DLBCL who had undergone at least one prior regimen. Patients received either Polivy plus bendamustine and rituximab or only bendamustine and rituximab for six 21-day cycles. At the completion of therapy, 40% of patients who received Polivy in conjunction with bendamustine and rituximab achieved a complete response, compared with 18% of patients who received only bendamustine and rituximab; total response was 63% in those who received Polivy and 25% in those who did not.
The most common adverse events included neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia. Serious adverse events occurred in 64% of patients, most commonly from infection; the most common cause for treatment discontinuation was cytopenia.
The recommended dose of Polivy is 1.8 mg/kg as an intravenous infusion over 90 minutes every 21 days for six cycles in combination with bendamustine and a rituximab product, the FDA said. Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated.
Find the full press release on the FDA website.
The Food and Drug Administration has granted accelerated approval to Polivy (polatuzumab vedotin-piiq), in conjunction with bendamustine and a rituximab product, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have undergone at least two prior therapies.
The FDA approval is based on results of an open-label, multicenter clinical trial of 80 patients with DLBCL who had undergone at least one prior regimen. Patients received either Polivy plus bendamustine and rituximab or only bendamustine and rituximab for six 21-day cycles. At the completion of therapy, 40% of patients who received Polivy in conjunction with bendamustine and rituximab achieved a complete response, compared with 18% of patients who received only bendamustine and rituximab; total response was 63% in those who received Polivy and 25% in those who did not.
The most common adverse events included neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia. Serious adverse events occurred in 64% of patients, most commonly from infection; the most common cause for treatment discontinuation was cytopenia.
The recommended dose of Polivy is 1.8 mg/kg as an intravenous infusion over 90 minutes every 21 days for six cycles in combination with bendamustine and a rituximab product, the FDA said. Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated.
Find the full press release on the FDA website.
Chemo-free Smart Start regimen looks promising in poor-prognosis DLBCL
CHICAGO – A chemotherapy-free regimen has produced promising early response and survival outcomes in patients with a particularly poor-prognosis subtype of diffuse large B-cell lymphoma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.
The overall response rate was 86% after two cycles of combined rituximab, lenalidomide, and ibrutinib – or RLI – in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) of the non–germinal center (non-GCB) subtype, said Jason Westin, MD, of the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center in Houston.
The response rate increased to 96% after subsequent cycles of RLI plus standard chemotherapy, said Dr.Westin, who added that the rates of progression-free and overall survival at 1 year were also 96% in the investigator initiated, single-arm, open-label, phase 2 study, called Smart Start.
That looks quite favorable, compared with what’s been achieved in previous studies in this poor-prognosis group of patients, Dr. Westin said during a podium presentation of Smart Start data, though he cautioned against direct comparison to historical studies and added that further follow-up is needed.
“Our survival outcomes appear excellent with about a year’s worth of follow-up,” he said during his presentation. “I’d say the novel/novel combinations, with and without chemotherapy, are feasible for large cell, and next step studies are warranted.”
Jasmine M. Zain, MD, of City of Hope Comprehensive Cancer Center, said these results so far raise the possibility of an effective chemotherapy-free treatment regimen for aggressive lymphomas.
“This regimen, particularly for non-GCB subtypes, is extremely promising,” Dr. Zain said during a podium discussion of the study. “I think we were all oohing and aahing over the results, and it could possibly even be practice changing.”
Moving to a nonchemotherapy regimen could raise new questions for treatment of non-GCB and possibly also GCB subtypes of DLBCL, such as when the treatments could be stopped, or whether a maintenance approach would be useful, she added.
The Smart Start study enrolled a total of 60 patients with non-GCB DLBCL. The patients received RLI for two 21-day cycles, followed by another six cycles of RLI plus chemotherapy, which was either EPOCH or CHOP, at the investigators’ discretion.
“With a median follow-up of 362 days, we’ve had three progression events,” Dr. Westin said in his discussion of the preliminary efficacy results.
Adverse events were similar to what would be expected for standard chemotherapy, according to Dr. Westin, except for rash, which was seen mainly in cycles one and two.
There were two deaths on study protocol, including one fatal fungal infection that investigators attributed to high dose corticosteroids and RLI. There were no subsequent fungal infections after a protocol amendment prohibiting corticosteroids during the RLI-only cycles, according to the investigators’ report.
The high response rates following the initial lead-in phase made investigators wonder what would happen without subsequent chemotherapy, Dr. Westin told attendees during his oral presentation. In one case, a 74-year-old man did complete the two lead-in cycles of RLI and declined further therapy.
“He’s now nearly 2 years out, without any additional therapy, and has not relapsed to date,” Dr. Westin said. “This is, again, with 6 weeks worth of RLI therapy.”
Final results and minimal residual disease data from the Smart Start study will be presented at a conference later in 2019, Dr. Westin said.
The study received research support and funding from the ASCO Conquer Cancer Foundation. The trial drug and support were provided by Celgene and Janssen. Dr. Westin reported disclosures related to Celgene, Genentech/Abbvie, Kite Pharma, Kite/Gilead, Novartis, ProNAi, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Janssen, and Karyopharm Therapeutics.
SOURCE: Westin J et al. ASCO 2019, Abstract 7508.
CHICAGO – A chemotherapy-free regimen has produced promising early response and survival outcomes in patients with a particularly poor-prognosis subtype of diffuse large B-cell lymphoma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.
The overall response rate was 86% after two cycles of combined rituximab, lenalidomide, and ibrutinib – or RLI – in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) of the non–germinal center (non-GCB) subtype, said Jason Westin, MD, of the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center in Houston.
The response rate increased to 96% after subsequent cycles of RLI plus standard chemotherapy, said Dr.Westin, who added that the rates of progression-free and overall survival at 1 year were also 96% in the investigator initiated, single-arm, open-label, phase 2 study, called Smart Start.
That looks quite favorable, compared with what’s been achieved in previous studies in this poor-prognosis group of patients, Dr. Westin said during a podium presentation of Smart Start data, though he cautioned against direct comparison to historical studies and added that further follow-up is needed.
“Our survival outcomes appear excellent with about a year’s worth of follow-up,” he said during his presentation. “I’d say the novel/novel combinations, with and without chemotherapy, are feasible for large cell, and next step studies are warranted.”
Jasmine M. Zain, MD, of City of Hope Comprehensive Cancer Center, said these results so far raise the possibility of an effective chemotherapy-free treatment regimen for aggressive lymphomas.
“This regimen, particularly for non-GCB subtypes, is extremely promising,” Dr. Zain said during a podium discussion of the study. “I think we were all oohing and aahing over the results, and it could possibly even be practice changing.”
Moving to a nonchemotherapy regimen could raise new questions for treatment of non-GCB and possibly also GCB subtypes of DLBCL, such as when the treatments could be stopped, or whether a maintenance approach would be useful, she added.
The Smart Start study enrolled a total of 60 patients with non-GCB DLBCL. The patients received RLI for two 21-day cycles, followed by another six cycles of RLI plus chemotherapy, which was either EPOCH or CHOP, at the investigators’ discretion.
“With a median follow-up of 362 days, we’ve had three progression events,” Dr. Westin said in his discussion of the preliminary efficacy results.
Adverse events were similar to what would be expected for standard chemotherapy, according to Dr. Westin, except for rash, which was seen mainly in cycles one and two.
There were two deaths on study protocol, including one fatal fungal infection that investigators attributed to high dose corticosteroids and RLI. There were no subsequent fungal infections after a protocol amendment prohibiting corticosteroids during the RLI-only cycles, according to the investigators’ report.
The high response rates following the initial lead-in phase made investigators wonder what would happen without subsequent chemotherapy, Dr. Westin told attendees during his oral presentation. In one case, a 74-year-old man did complete the two lead-in cycles of RLI and declined further therapy.
“He’s now nearly 2 years out, without any additional therapy, and has not relapsed to date,” Dr. Westin said. “This is, again, with 6 weeks worth of RLI therapy.”
Final results and minimal residual disease data from the Smart Start study will be presented at a conference later in 2019, Dr. Westin said.
The study received research support and funding from the ASCO Conquer Cancer Foundation. The trial drug and support were provided by Celgene and Janssen. Dr. Westin reported disclosures related to Celgene, Genentech/Abbvie, Kite Pharma, Kite/Gilead, Novartis, ProNAi, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Janssen, and Karyopharm Therapeutics.
SOURCE: Westin J et al. ASCO 2019, Abstract 7508.
CHICAGO – A chemotherapy-free regimen has produced promising early response and survival outcomes in patients with a particularly poor-prognosis subtype of diffuse large B-cell lymphoma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.
The overall response rate was 86% after two cycles of combined rituximab, lenalidomide, and ibrutinib – or RLI – in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) of the non–germinal center (non-GCB) subtype, said Jason Westin, MD, of the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center in Houston.
The response rate increased to 96% after subsequent cycles of RLI plus standard chemotherapy, said Dr.Westin, who added that the rates of progression-free and overall survival at 1 year were also 96% in the investigator initiated, single-arm, open-label, phase 2 study, called Smart Start.
That looks quite favorable, compared with what’s been achieved in previous studies in this poor-prognosis group of patients, Dr. Westin said during a podium presentation of Smart Start data, though he cautioned against direct comparison to historical studies and added that further follow-up is needed.
“Our survival outcomes appear excellent with about a year’s worth of follow-up,” he said during his presentation. “I’d say the novel/novel combinations, with and without chemotherapy, are feasible for large cell, and next step studies are warranted.”
Jasmine M. Zain, MD, of City of Hope Comprehensive Cancer Center, said these results so far raise the possibility of an effective chemotherapy-free treatment regimen for aggressive lymphomas.
“This regimen, particularly for non-GCB subtypes, is extremely promising,” Dr. Zain said during a podium discussion of the study. “I think we were all oohing and aahing over the results, and it could possibly even be practice changing.”
Moving to a nonchemotherapy regimen could raise new questions for treatment of non-GCB and possibly also GCB subtypes of DLBCL, such as when the treatments could be stopped, or whether a maintenance approach would be useful, she added.
The Smart Start study enrolled a total of 60 patients with non-GCB DLBCL. The patients received RLI for two 21-day cycles, followed by another six cycles of RLI plus chemotherapy, which was either EPOCH or CHOP, at the investigators’ discretion.
“With a median follow-up of 362 days, we’ve had three progression events,” Dr. Westin said in his discussion of the preliminary efficacy results.
Adverse events were similar to what would be expected for standard chemotherapy, according to Dr. Westin, except for rash, which was seen mainly in cycles one and two.
There were two deaths on study protocol, including one fatal fungal infection that investigators attributed to high dose corticosteroids and RLI. There were no subsequent fungal infections after a protocol amendment prohibiting corticosteroids during the RLI-only cycles, according to the investigators’ report.
The high response rates following the initial lead-in phase made investigators wonder what would happen without subsequent chemotherapy, Dr. Westin told attendees during his oral presentation. In one case, a 74-year-old man did complete the two lead-in cycles of RLI and declined further therapy.
“He’s now nearly 2 years out, without any additional therapy, and has not relapsed to date,” Dr. Westin said. “This is, again, with 6 weeks worth of RLI therapy.”
Final results and minimal residual disease data from the Smart Start study will be presented at a conference later in 2019, Dr. Westin said.
The study received research support and funding from the ASCO Conquer Cancer Foundation. The trial drug and support were provided by Celgene and Janssen. Dr. Westin reported disclosures related to Celgene, Genentech/Abbvie, Kite Pharma, Kite/Gilead, Novartis, ProNAi, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Janssen, and Karyopharm Therapeutics.
SOURCE: Westin J et al. ASCO 2019, Abstract 7508.
REPORTING FROM ASCO 2019
Daratumumab regimen shows benefit in transplant-ineligible myeloma
For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT), adding daratumumab to lenalidomide and dexamethasone provides better outcomes than standard therapy alone, based on an interim analysis from the phase 3 MAIA trial.
A greater proportion of patients in the daratumumab group had complete responses and were alive without disease progression after a median follow-up of 28 months, reported lead author Thierry Facon, MD, of the University of Lille (France) and colleagues, who also noted that daratumumab was associated with higher rates of grade 3 or 4 pneumonia, neutropenia, and lymphopenia.
“For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care,” the investigators wrote in the New England Journal of Medicine.
The findings from MAIA add clarity to the efficacy and safety of daratumumab in this setting, building on previous phase 3 myeloma trials in the same area, such as ALCYONE, CASTOR, and POLLUX, the investigators noted.
MAIA was an open-label, international trial involving 737 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized in a 1:1 ratio to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group; n = 368) or lenalidomide and dexamethasone alone (control group; n = 369).
On a 28-day cycle, all patients received oral lenalidomide 25 mg on days 1-21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the daratumumab group received intravenous daratumumab dosed at 16 mg/kg once a week for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter. Treatment was continued until unacceptable toxic effects or disease progression occurred.
The primary end point was progression-free survival (PFS). Various secondary end points were also evaluated, including time to progression, complete responses, overall survival, and others.
Among the 737 randomized patients, 729 ultimately underwent treatment. The median patient age was 73 years.
Generally, efficacy measures favored adding daratumumab. After a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% of patients in the daratumumab group, compared with 38.8% in the control group.
The median PFS was not reached in the daratumumab group, compared with 31.9 months in the control group. There was a 44% lower risk of disease progression or death among patients who received daratumumab, compared with the control group (hazard ratio, 0.56, P less than .001).
This PFS trend was consistent across most subgroups, including those for sex, age, and race, with the exception of patients with baseline hepatic impairment.
Additional efficacy measures added weight to the apparent benefit of adding daratumumab. For instance, more patients in the daratumumab group achieved a complete response or better (47.6% vs. 24.9%) and were negative for minimum residual disease (24.2% vs. 7.3%).
In terms of safety, more patients in the daratumumab group than the control group developed grade 3 or higher neutropenia (50% vs. 35.3%), lymphopenia (15.1% vs. 10.7%), infections (32.1% vs. 23.3%) or pneumonia (13.7% vs. 7.9%).
In contrast, grade 3 or 4 anemia was less common in the daratumumab group than the control group (11.8% vs. 19.7%). Overall, the rate of serious adverse events was similar for both groups (approximately 63%), as was the rate of adverse events resulting in death (approximately 6%-7%).
“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” the investigators concluded.
The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.
SOURCE: Facon T et al. N Engl J Med. 2019;380:2104-15.
The findings from the phase 3 MAIA trial highlight the “superior efficacy” of adding daratumumab to lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma who are ineligible for stem cell transplantation, Jacob Laubach, MD, commented in an accompanying editorial.
Dr. Laubach noted several important clinical implications of the study findings, including that the use of CD38-targeting monoclonal antibody therapy was associated with a significant improvement in the number of patients who had a complete response to therapy and who were negative for minimal residual disease.
However, with daratumumab as a component of induction and maintenance therapy for patients with multiple myeloma who are ineligible for transplantation, it is important to consider the feasibility of retreatment with CD38-targeting therapy in patients who become resistant to daratumumab-containing regimens.
Jacob Laubach, MD, is at the Dana-Farber Cancer Institute in Boston. He reported having no financial disclosures. He made his remarks in an editorial in the New England Journal of Medicine (2019;380:2172-3).
The findings from the phase 3 MAIA trial highlight the “superior efficacy” of adding daratumumab to lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma who are ineligible for stem cell transplantation, Jacob Laubach, MD, commented in an accompanying editorial.
Dr. Laubach noted several important clinical implications of the study findings, including that the use of CD38-targeting monoclonal antibody therapy was associated with a significant improvement in the number of patients who had a complete response to therapy and who were negative for minimal residual disease.
However, with daratumumab as a component of induction and maintenance therapy for patients with multiple myeloma who are ineligible for transplantation, it is important to consider the feasibility of retreatment with CD38-targeting therapy in patients who become resistant to daratumumab-containing regimens.
Jacob Laubach, MD, is at the Dana-Farber Cancer Institute in Boston. He reported having no financial disclosures. He made his remarks in an editorial in the New England Journal of Medicine (2019;380:2172-3).
The findings from the phase 3 MAIA trial highlight the “superior efficacy” of adding daratumumab to lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma who are ineligible for stem cell transplantation, Jacob Laubach, MD, commented in an accompanying editorial.
Dr. Laubach noted several important clinical implications of the study findings, including that the use of CD38-targeting monoclonal antibody therapy was associated with a significant improvement in the number of patients who had a complete response to therapy and who were negative for minimal residual disease.
However, with daratumumab as a component of induction and maintenance therapy for patients with multiple myeloma who are ineligible for transplantation, it is important to consider the feasibility of retreatment with CD38-targeting therapy in patients who become resistant to daratumumab-containing regimens.
Jacob Laubach, MD, is at the Dana-Farber Cancer Institute in Boston. He reported having no financial disclosures. He made his remarks in an editorial in the New England Journal of Medicine (2019;380:2172-3).
For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT), adding daratumumab to lenalidomide and dexamethasone provides better outcomes than standard therapy alone, based on an interim analysis from the phase 3 MAIA trial.
A greater proportion of patients in the daratumumab group had complete responses and were alive without disease progression after a median follow-up of 28 months, reported lead author Thierry Facon, MD, of the University of Lille (France) and colleagues, who also noted that daratumumab was associated with higher rates of grade 3 or 4 pneumonia, neutropenia, and lymphopenia.
“For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care,” the investigators wrote in the New England Journal of Medicine.
The findings from MAIA add clarity to the efficacy and safety of daratumumab in this setting, building on previous phase 3 myeloma trials in the same area, such as ALCYONE, CASTOR, and POLLUX, the investigators noted.
MAIA was an open-label, international trial involving 737 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized in a 1:1 ratio to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group; n = 368) or lenalidomide and dexamethasone alone (control group; n = 369).
On a 28-day cycle, all patients received oral lenalidomide 25 mg on days 1-21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the daratumumab group received intravenous daratumumab dosed at 16 mg/kg once a week for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter. Treatment was continued until unacceptable toxic effects or disease progression occurred.
The primary end point was progression-free survival (PFS). Various secondary end points were also evaluated, including time to progression, complete responses, overall survival, and others.
Among the 737 randomized patients, 729 ultimately underwent treatment. The median patient age was 73 years.
Generally, efficacy measures favored adding daratumumab. After a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% of patients in the daratumumab group, compared with 38.8% in the control group.
The median PFS was not reached in the daratumumab group, compared with 31.9 months in the control group. There was a 44% lower risk of disease progression or death among patients who received daratumumab, compared with the control group (hazard ratio, 0.56, P less than .001).
This PFS trend was consistent across most subgroups, including those for sex, age, and race, with the exception of patients with baseline hepatic impairment.
Additional efficacy measures added weight to the apparent benefit of adding daratumumab. For instance, more patients in the daratumumab group achieved a complete response or better (47.6% vs. 24.9%) and were negative for minimum residual disease (24.2% vs. 7.3%).
In terms of safety, more patients in the daratumumab group than the control group developed grade 3 or higher neutropenia (50% vs. 35.3%), lymphopenia (15.1% vs. 10.7%), infections (32.1% vs. 23.3%) or pneumonia (13.7% vs. 7.9%).
In contrast, grade 3 or 4 anemia was less common in the daratumumab group than the control group (11.8% vs. 19.7%). Overall, the rate of serious adverse events was similar for both groups (approximately 63%), as was the rate of adverse events resulting in death (approximately 6%-7%).
“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” the investigators concluded.
The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.
SOURCE: Facon T et al. N Engl J Med. 2019;380:2104-15.
For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT), adding daratumumab to lenalidomide and dexamethasone provides better outcomes than standard therapy alone, based on an interim analysis from the phase 3 MAIA trial.
A greater proportion of patients in the daratumumab group had complete responses and were alive without disease progression after a median follow-up of 28 months, reported lead author Thierry Facon, MD, of the University of Lille (France) and colleagues, who also noted that daratumumab was associated with higher rates of grade 3 or 4 pneumonia, neutropenia, and lymphopenia.
“For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care,” the investigators wrote in the New England Journal of Medicine.
The findings from MAIA add clarity to the efficacy and safety of daratumumab in this setting, building on previous phase 3 myeloma trials in the same area, such as ALCYONE, CASTOR, and POLLUX, the investigators noted.
MAIA was an open-label, international trial involving 737 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized in a 1:1 ratio to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group; n = 368) or lenalidomide and dexamethasone alone (control group; n = 369).
On a 28-day cycle, all patients received oral lenalidomide 25 mg on days 1-21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the daratumumab group received intravenous daratumumab dosed at 16 mg/kg once a week for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter. Treatment was continued until unacceptable toxic effects or disease progression occurred.
The primary end point was progression-free survival (PFS). Various secondary end points were also evaluated, including time to progression, complete responses, overall survival, and others.
Among the 737 randomized patients, 729 ultimately underwent treatment. The median patient age was 73 years.
Generally, efficacy measures favored adding daratumumab. After a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% of patients in the daratumumab group, compared with 38.8% in the control group.
The median PFS was not reached in the daratumumab group, compared with 31.9 months in the control group. There was a 44% lower risk of disease progression or death among patients who received daratumumab, compared with the control group (hazard ratio, 0.56, P less than .001).
This PFS trend was consistent across most subgroups, including those for sex, age, and race, with the exception of patients with baseline hepatic impairment.
Additional efficacy measures added weight to the apparent benefit of adding daratumumab. For instance, more patients in the daratumumab group achieved a complete response or better (47.6% vs. 24.9%) and were negative for minimum residual disease (24.2% vs. 7.3%).
In terms of safety, more patients in the daratumumab group than the control group developed grade 3 or higher neutropenia (50% vs. 35.3%), lymphopenia (15.1% vs. 10.7%), infections (32.1% vs. 23.3%) or pneumonia (13.7% vs. 7.9%).
In contrast, grade 3 or 4 anemia was less common in the daratumumab group than the control group (11.8% vs. 19.7%). Overall, the rate of serious adverse events was similar for both groups (approximately 63%), as was the rate of adverse events resulting in death (approximately 6%-7%).
“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” the investigators concluded.
The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.
SOURCE: Facon T et al. N Engl J Med. 2019;380:2104-15.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation, adding daratumumab to lenalidomide and dexamethasone standard therapy provides better outcomes than standard therapy alone.
Major finding: After 28-month follow-up, 26.4% of patients in the daratumumab group had disease progression or died, compared with 38.8% in the control group.
Study details: A randomized, open-label, phase 3 trial involving 737 patients with newly diagnosed multiple myeloma.
Disclosures: The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.
Source: Facon T et al. N Engl J Med. 2019;380:2104-15.
FDA approves lenalidomide/rituximab for previously treated FL, MZL
The Food and Drug Administration has approved lenalidomide (Revlimid), in combination with rituximab, for the treatment of adult patients with previously treated follicular or marginal zone lymphoma.
FDA approval is based on results from the randomized, double-blind, phase 3 AUGMENT trial, which evaluated lenalidomide/rituximab versus rituximab and placebo in patients with previously treated follicular or marginal zone lymphoma. The median progression-free survival in those receiving lenalidomide/rituximab was 39.4 months, compared with 14.1 months for those receiving rituximab/placebo (odds ratio, 0.46; 95% confidence interval, 0.34-0.62; P less than .0001).
A numeric trend was seen in overall survival over the follow-up period of 28.3 months (16 vs. 26 deaths; hazard ratio, 0.61; 95% CI, 0.33-1.13).
The most common adverse events associated with lenalidomide/rituximab are neutropenia, diarrhea, constipation, cough, fatigue, rash, pyrexia, leukopenia, pruritus, upper respiratory tract infections, abdominal pain, anemia, headache, and thrombocytopenia. Lenalidomide also contains a boxed warning for embryo-fetal toxicity, hematologic toxicity, and venous and arterial thromboembolism.
“Chemotherapy continues to be a standard of care for indolent forms of NHL, but most patients will relapse or become refractory to their current treatment. This approval represents a new therapeutic option for previously treated patients with follicular and marginal zone lymphomas, including those who relapse or no longer respond to initial treatment,” Meghan Gutierrez, CEO of the Lymphoma Research Foundation, said in a statement.
The Food and Drug Administration has approved lenalidomide (Revlimid), in combination with rituximab, for the treatment of adult patients with previously treated follicular or marginal zone lymphoma.
FDA approval is based on results from the randomized, double-blind, phase 3 AUGMENT trial, which evaluated lenalidomide/rituximab versus rituximab and placebo in patients with previously treated follicular or marginal zone lymphoma. The median progression-free survival in those receiving lenalidomide/rituximab was 39.4 months, compared with 14.1 months for those receiving rituximab/placebo (odds ratio, 0.46; 95% confidence interval, 0.34-0.62; P less than .0001).
A numeric trend was seen in overall survival over the follow-up period of 28.3 months (16 vs. 26 deaths; hazard ratio, 0.61; 95% CI, 0.33-1.13).
The most common adverse events associated with lenalidomide/rituximab are neutropenia, diarrhea, constipation, cough, fatigue, rash, pyrexia, leukopenia, pruritus, upper respiratory tract infections, abdominal pain, anemia, headache, and thrombocytopenia. Lenalidomide also contains a boxed warning for embryo-fetal toxicity, hematologic toxicity, and venous and arterial thromboembolism.
“Chemotherapy continues to be a standard of care for indolent forms of NHL, but most patients will relapse or become refractory to their current treatment. This approval represents a new therapeutic option for previously treated patients with follicular and marginal zone lymphomas, including those who relapse or no longer respond to initial treatment,” Meghan Gutierrez, CEO of the Lymphoma Research Foundation, said in a statement.
The Food and Drug Administration has approved lenalidomide (Revlimid), in combination with rituximab, for the treatment of adult patients with previously treated follicular or marginal zone lymphoma.
FDA approval is based on results from the randomized, double-blind, phase 3 AUGMENT trial, which evaluated lenalidomide/rituximab versus rituximab and placebo in patients with previously treated follicular or marginal zone lymphoma. The median progression-free survival in those receiving lenalidomide/rituximab was 39.4 months, compared with 14.1 months for those receiving rituximab/placebo (odds ratio, 0.46; 95% confidence interval, 0.34-0.62; P less than .0001).
A numeric trend was seen in overall survival over the follow-up period of 28.3 months (16 vs. 26 deaths; hazard ratio, 0.61; 95% CI, 0.33-1.13).
The most common adverse events associated with lenalidomide/rituximab are neutropenia, diarrhea, constipation, cough, fatigue, rash, pyrexia, leukopenia, pruritus, upper respiratory tract infections, abdominal pain, anemia, headache, and thrombocytopenia. Lenalidomide also contains a boxed warning for embryo-fetal toxicity, hematologic toxicity, and venous and arterial thromboembolism.
“Chemotherapy continues to be a standard of care for indolent forms of NHL, but most patients will relapse or become refractory to their current treatment. This approval represents a new therapeutic option for previously treated patients with follicular and marginal zone lymphomas, including those who relapse or no longer respond to initial treatment,” Meghan Gutierrez, CEO of the Lymphoma Research Foundation, said in a statement.
CD23 expression linked to improved survival in MCL
In a large cohort of patients with mantle cell lymphoma (MCL), CD23 expression was associated with significantly improved survival outcomes, according to a retrospective analysis.
“Mantle cell lymphoma has a distinctive immunophenotype, typically positive for pan B-cell markers, CD5 and cyclin D1, but negative for CD10, CD23, and CD200. Although most cases show this immunophenotype, some MCL cases have atypical immunophenotypic features, such as expression of CD10, CD23, or rarely CD200 or lack of expression of CD5,” wrote Annapurna Saksena, MD, of MD Anderson Cancer Center, Houston, and colleagues. Their report is in Human Pathology.
They retrospectively reviewed medical records from a pathology database at MD Anderson from the period of 2008-2016. In all, 798 patients with MCL were identified, of which 103 were classified as CD23-positive via flow cytometry.
The team collected data related to the immunophenotypic and clinicopathologic characteristics of the disease, in addition to survival-related outcomes, including progression-free survival (PFS) and overall survival (OS). They compared outcomes for the CD23-positive group against 240 patients with CD23-negative MCL.
After analysis, Dr. Saksena and colleagues found that patients with CD23-positive MCL more frequently had bone marrow involvement (89% vs. 78%, P = .02), a leukemic nonnodal presentation (42% vs. 11%, P = .0001), an elevated leukocyte count (33% vs. 18%, P = .009), and stage 4 disease (87% vs. 77%, P = .03).
The researchers reported that CD23 expression was associated with significantly improved PFS and OS (P = .029 and P = .02, respectively) in the univariate analysis.
However, the prognostic significance was partially lost when leukemic nonnodal cases were excluded, the researchers reported.
In addition to the higher frequency of leukemic nonnodal presentation with CD23-positive MCL cases, there was a higher frequency of CD200 expression and a lower frequency of SOX11 expression.
The researchers acknowledged that a key limitation of the study was the loss of prognostic significance in the multivariate analysis. Further studies are needed to fully understand the links between CD23 expression and MCL survival, they noted.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: Saksena A et al. Hum Pathol. 2019 May 2. doi: 10.1016/j.humpath.2019.04.010.
In a large cohort of patients with mantle cell lymphoma (MCL), CD23 expression was associated with significantly improved survival outcomes, according to a retrospective analysis.
“Mantle cell lymphoma has a distinctive immunophenotype, typically positive for pan B-cell markers, CD5 and cyclin D1, but negative for CD10, CD23, and CD200. Although most cases show this immunophenotype, some MCL cases have atypical immunophenotypic features, such as expression of CD10, CD23, or rarely CD200 or lack of expression of CD5,” wrote Annapurna Saksena, MD, of MD Anderson Cancer Center, Houston, and colleagues. Their report is in Human Pathology.
They retrospectively reviewed medical records from a pathology database at MD Anderson from the period of 2008-2016. In all, 798 patients with MCL were identified, of which 103 were classified as CD23-positive via flow cytometry.
The team collected data related to the immunophenotypic and clinicopathologic characteristics of the disease, in addition to survival-related outcomes, including progression-free survival (PFS) and overall survival (OS). They compared outcomes for the CD23-positive group against 240 patients with CD23-negative MCL.
After analysis, Dr. Saksena and colleagues found that patients with CD23-positive MCL more frequently had bone marrow involvement (89% vs. 78%, P = .02), a leukemic nonnodal presentation (42% vs. 11%, P = .0001), an elevated leukocyte count (33% vs. 18%, P = .009), and stage 4 disease (87% vs. 77%, P = .03).
The researchers reported that CD23 expression was associated with significantly improved PFS and OS (P = .029 and P = .02, respectively) in the univariate analysis.
However, the prognostic significance was partially lost when leukemic nonnodal cases were excluded, the researchers reported.
In addition to the higher frequency of leukemic nonnodal presentation with CD23-positive MCL cases, there was a higher frequency of CD200 expression and a lower frequency of SOX11 expression.
The researchers acknowledged that a key limitation of the study was the loss of prognostic significance in the multivariate analysis. Further studies are needed to fully understand the links between CD23 expression and MCL survival, they noted.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: Saksena A et al. Hum Pathol. 2019 May 2. doi: 10.1016/j.humpath.2019.04.010.
In a large cohort of patients with mantle cell lymphoma (MCL), CD23 expression was associated with significantly improved survival outcomes, according to a retrospective analysis.
“Mantle cell lymphoma has a distinctive immunophenotype, typically positive for pan B-cell markers, CD5 and cyclin D1, but negative for CD10, CD23, and CD200. Although most cases show this immunophenotype, some MCL cases have atypical immunophenotypic features, such as expression of CD10, CD23, or rarely CD200 or lack of expression of CD5,” wrote Annapurna Saksena, MD, of MD Anderson Cancer Center, Houston, and colleagues. Their report is in Human Pathology.
They retrospectively reviewed medical records from a pathology database at MD Anderson from the period of 2008-2016. In all, 798 patients with MCL were identified, of which 103 were classified as CD23-positive via flow cytometry.
The team collected data related to the immunophenotypic and clinicopathologic characteristics of the disease, in addition to survival-related outcomes, including progression-free survival (PFS) and overall survival (OS). They compared outcomes for the CD23-positive group against 240 patients with CD23-negative MCL.
After analysis, Dr. Saksena and colleagues found that patients with CD23-positive MCL more frequently had bone marrow involvement (89% vs. 78%, P = .02), a leukemic nonnodal presentation (42% vs. 11%, P = .0001), an elevated leukocyte count (33% vs. 18%, P = .009), and stage 4 disease (87% vs. 77%, P = .03).
The researchers reported that CD23 expression was associated with significantly improved PFS and OS (P = .029 and P = .02, respectively) in the univariate analysis.
However, the prognostic significance was partially lost when leukemic nonnodal cases were excluded, the researchers reported.
In addition to the higher frequency of leukemic nonnodal presentation with CD23-positive MCL cases, there was a higher frequency of CD200 expression and a lower frequency of SOX11 expression.
The researchers acknowledged that a key limitation of the study was the loss of prognostic significance in the multivariate analysis. Further studies are needed to fully understand the links between CD23 expression and MCL survival, they noted.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: Saksena A et al. Hum Pathol. 2019 May 2. doi: 10.1016/j.humpath.2019.04.010.
FROM HUMAN PATHOLOGY
Lenalidomide may reduce risk of progression from SMM to MM
Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.
At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.
However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.
These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.
A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.
With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.
The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.
In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.
Safety
Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.
The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.
Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
Efficacy
“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”
In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.
In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.
“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”
Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.
SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.
Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.
At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.
However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.
These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.
A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.
With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.
The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.
In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.
Safety
Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.
The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.
Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
Efficacy
“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”
In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.
In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.
“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”
Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.
SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.
Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.
At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.
However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.
These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.
Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.
A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.
With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.
The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.
In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.
Safety
Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.
The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.
Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
Efficacy
“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”
In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.
In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.
“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”
Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.
SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.
REPORTING FROM ASCO 2019
Trial follow-up spotlights survival gains in follicular lymphoma
Results from a 13-year follow-up of a trial comparing two types of rituximab-based chemotherapy as upfront treatment for patients with follicular lymphoma show an “extraordinary improvement” in overall survival, compared with the prerituximab era.
In a finding that the researchers termed “somewhat unexpected,” complete remission was the strongest factor in long-term survival.
Between March 2000 and May 2005, researchers enrolled 136 high-risk follicular lymphoma patients in the GITMO-IIL trial to evaluate the superiority of high-dose chemotherapy with rituximab and autograft (R-HDS) versus conventional chemotherapy with rituximab (R-CHOP) as frontline therapy. At a median follow-up of 4 years, there was no survival advantage for R-HDS.
In the current analysis – that had a 13-year median follow-up – median survival had not yet been reached. As of February 2017, two-thirds of all patients were alive at their last follow-up. Overall survival was 68.5% in the R-CHOP arm and 64.5% in the R-HDS arm, Riccardo Bruna, MD, of the European Institute of Oncology in Milano, Italy, and his colleagues, reported in Haematologica.
The main causes of death for the 46 patients who had died as of long-term follow-up were disease progression and secondary malignancies. Other causes included cardiovascular events, infections, graft failure following autograft, anaphylactic shock, and late sudden death.
Complete remission was seen in 98 patients (73.1%) overall – 59.1% in the R-CHOP arm and 86.7% in the R-HDS arm. Achieving durable complete remission was associated with prolonged survival, the researchers reported. Of the 79 patients in complete remission at 2 years after the start of treatment, 65 (82.3%) were alive at 13 years, compared with 21 (58.3%) of 36 patients who had an early relapse (P = .003).
“[Complete remission] achievement was the most important factor for prolonged survival,” the researchers wrote. “The importance of disease response is further emphasized by the first-time observation that [molecular remission] achievement is associated with survival duration and a high proportion of patients had prolonged survival in the absence of disease recurrence.”
The researchers reported that this is longest ever follow-up reported for first-line treatment of follicular lymphoma with rituximab-based chemotherapy.
This work was supported in part by the Ministero Italiano Università e Ricerca and by Banca del Piemonte. The initial clinical trial was supported by Compagnia di San Paolo, Regione Piemonte, and Roche, which provided rituximab for the study.
SOURCE: Bruna R et al. Haematologica. 2019 Apr 11. doi: 10.3324/haematol.2018.209932.
Results from a 13-year follow-up of a trial comparing two types of rituximab-based chemotherapy as upfront treatment for patients with follicular lymphoma show an “extraordinary improvement” in overall survival, compared with the prerituximab era.
In a finding that the researchers termed “somewhat unexpected,” complete remission was the strongest factor in long-term survival.
Between March 2000 and May 2005, researchers enrolled 136 high-risk follicular lymphoma patients in the GITMO-IIL trial to evaluate the superiority of high-dose chemotherapy with rituximab and autograft (R-HDS) versus conventional chemotherapy with rituximab (R-CHOP) as frontline therapy. At a median follow-up of 4 years, there was no survival advantage for R-HDS.
In the current analysis – that had a 13-year median follow-up – median survival had not yet been reached. As of February 2017, two-thirds of all patients were alive at their last follow-up. Overall survival was 68.5% in the R-CHOP arm and 64.5% in the R-HDS arm, Riccardo Bruna, MD, of the European Institute of Oncology in Milano, Italy, and his colleagues, reported in Haematologica.
The main causes of death for the 46 patients who had died as of long-term follow-up were disease progression and secondary malignancies. Other causes included cardiovascular events, infections, graft failure following autograft, anaphylactic shock, and late sudden death.
Complete remission was seen in 98 patients (73.1%) overall – 59.1% in the R-CHOP arm and 86.7% in the R-HDS arm. Achieving durable complete remission was associated with prolonged survival, the researchers reported. Of the 79 patients in complete remission at 2 years after the start of treatment, 65 (82.3%) were alive at 13 years, compared with 21 (58.3%) of 36 patients who had an early relapse (P = .003).
“[Complete remission] achievement was the most important factor for prolonged survival,” the researchers wrote. “The importance of disease response is further emphasized by the first-time observation that [molecular remission] achievement is associated with survival duration and a high proportion of patients had prolonged survival in the absence of disease recurrence.”
The researchers reported that this is longest ever follow-up reported for first-line treatment of follicular lymphoma with rituximab-based chemotherapy.
This work was supported in part by the Ministero Italiano Università e Ricerca and by Banca del Piemonte. The initial clinical trial was supported by Compagnia di San Paolo, Regione Piemonte, and Roche, which provided rituximab for the study.
SOURCE: Bruna R et al. Haematologica. 2019 Apr 11. doi: 10.3324/haematol.2018.209932.
Results from a 13-year follow-up of a trial comparing two types of rituximab-based chemotherapy as upfront treatment for patients with follicular lymphoma show an “extraordinary improvement” in overall survival, compared with the prerituximab era.
In a finding that the researchers termed “somewhat unexpected,” complete remission was the strongest factor in long-term survival.
Between March 2000 and May 2005, researchers enrolled 136 high-risk follicular lymphoma patients in the GITMO-IIL trial to evaluate the superiority of high-dose chemotherapy with rituximab and autograft (R-HDS) versus conventional chemotherapy with rituximab (R-CHOP) as frontline therapy. At a median follow-up of 4 years, there was no survival advantage for R-HDS.
In the current analysis – that had a 13-year median follow-up – median survival had not yet been reached. As of February 2017, two-thirds of all patients were alive at their last follow-up. Overall survival was 68.5% in the R-CHOP arm and 64.5% in the R-HDS arm, Riccardo Bruna, MD, of the European Institute of Oncology in Milano, Italy, and his colleagues, reported in Haematologica.
The main causes of death for the 46 patients who had died as of long-term follow-up were disease progression and secondary malignancies. Other causes included cardiovascular events, infections, graft failure following autograft, anaphylactic shock, and late sudden death.
Complete remission was seen in 98 patients (73.1%) overall – 59.1% in the R-CHOP arm and 86.7% in the R-HDS arm. Achieving durable complete remission was associated with prolonged survival, the researchers reported. Of the 79 patients in complete remission at 2 years after the start of treatment, 65 (82.3%) were alive at 13 years, compared with 21 (58.3%) of 36 patients who had an early relapse (P = .003).
“[Complete remission] achievement was the most important factor for prolonged survival,” the researchers wrote. “The importance of disease response is further emphasized by the first-time observation that [molecular remission] achievement is associated with survival duration and a high proportion of patients had prolonged survival in the absence of disease recurrence.”
The researchers reported that this is longest ever follow-up reported for first-line treatment of follicular lymphoma with rituximab-based chemotherapy.
This work was supported in part by the Ministero Italiano Università e Ricerca and by Banca del Piemonte. The initial clinical trial was supported by Compagnia di San Paolo, Regione Piemonte, and Roche, which provided rituximab for the study.
SOURCE: Bruna R et al. Haematologica. 2019 Apr 11. doi: 10.3324/haematol.2018.209932.
FROM HAEMATOLOGICA
Atypical case of cutaneous MCL mimics SPTCL
An atypical case of cutaneous mantle cell lymphoma (MCL) with histomorphological features mimicking subcutaneous panniculitis-like T-cell lymphoma (SPTCL) highlights a “potential pitfall,” according to investigators.
This unusual case stresses the importance of molecular cytogenetics and/or immunohistochemistry for panniculitis-type lymphomas, reported lead author Caroline Laggis, MD of the University of Utah, Salt Lake City, and colleagues.
“While morphologic features of SPTCL, specifically rimming of adipocytes by neoplastic lymphoid cells, have been documented in other types of lymphomas, this case is exceptional in that the morphologic features of SPTCL are showed in secondary cutaneous involvement by MCL,” the investigators wrote. Their report is in Journal of Cutaneous Pathology.
The patient was a 69-year-old man who presented with 2-year history of night sweats and fever of unknown origin, and, closer to presentation, weight loss and tender bumps under the skin of his pelvic region.
Subsequent computed tomography and excisional lymph node biopsy led to a diagnosis of MCL, with a Mantle Cell Lymphoma International Prognostic Index of 5, suggesting aggressive, intermediate-risk disease. Further imaging showed involvement of the nasopharynx, and cervical and mediastinal lymph nodes.
Bendamustine and rituximab chemotherapy was given unremarkably until the final cycle, at which point the patient presented with tender subcutaneous nodules on his lower legs. Histopathology from punch biopsies revealed “a dense infiltrate of monomorphic, mitotically active lymphoid cells with infiltration between the deep dermal collagen and the adipocytes in subcutaneous fat,” the investigators wrote, noting that the infiltrative cells were blastoid and 70% expressed cyclin D1, supporting cutaneous involvement of his systemic MCL.
Treatment was switched to ibrutinib and selinexor via a clinical trial, which led to temporary improvement of leg lesions; when the lesions returned, biopsy was performed with the same histopathological result. Lenalidomide and rituximab were started, but without success, and disease spread to the central nervous system.
Another biopsy of the skin lesions again supported cutaneous MCL, with tumor cells rimming individual adipocytes.
Because of this atypical morphology, fluorescence in situ hybridization (FISH) was conducted, revealing t(11;14)(q13:32) positivity, thereby “confirming the diagnosis of cutaneous involvement by systemic MCL,” the investigators wrote.
Genomic sequencing revealed abnormalities of “ataxia-telangiectasia mutated, mechanistic target of rapamycin kinase (mTOR), BCL6 corepressor, and FAS-associated factor 1, as well as the expected mutation in IGH-CCND1, leading to cyclin D1 upregulation.”
Subsequent treatment was unsuccessful, and the patient died from his disease.
“The complex and central role that mTOR plays in adipose homeostasis may link our tumor to its preference to the adipose tissue, although further investigation is warranted regarding specific genomic alterations in lymphomas and the implications these mutations have in the involvement of tumor cells with cutaneous and adipose environments,” the investigators wrote.
The investigators did not report conflicts of interest.
SOURCE: Laggis C et al. 2019 Apr 8. doi:10.1111/cup.13471.
An atypical case of cutaneous mantle cell lymphoma (MCL) with histomorphological features mimicking subcutaneous panniculitis-like T-cell lymphoma (SPTCL) highlights a “potential pitfall,” according to investigators.
This unusual case stresses the importance of molecular cytogenetics and/or immunohistochemistry for panniculitis-type lymphomas, reported lead author Caroline Laggis, MD of the University of Utah, Salt Lake City, and colleagues.
“While morphologic features of SPTCL, specifically rimming of adipocytes by neoplastic lymphoid cells, have been documented in other types of lymphomas, this case is exceptional in that the morphologic features of SPTCL are showed in secondary cutaneous involvement by MCL,” the investigators wrote. Their report is in Journal of Cutaneous Pathology.
The patient was a 69-year-old man who presented with 2-year history of night sweats and fever of unknown origin, and, closer to presentation, weight loss and tender bumps under the skin of his pelvic region.
Subsequent computed tomography and excisional lymph node biopsy led to a diagnosis of MCL, with a Mantle Cell Lymphoma International Prognostic Index of 5, suggesting aggressive, intermediate-risk disease. Further imaging showed involvement of the nasopharynx, and cervical and mediastinal lymph nodes.
Bendamustine and rituximab chemotherapy was given unremarkably until the final cycle, at which point the patient presented with tender subcutaneous nodules on his lower legs. Histopathology from punch biopsies revealed “a dense infiltrate of monomorphic, mitotically active lymphoid cells with infiltration between the deep dermal collagen and the adipocytes in subcutaneous fat,” the investigators wrote, noting that the infiltrative cells were blastoid and 70% expressed cyclin D1, supporting cutaneous involvement of his systemic MCL.
Treatment was switched to ibrutinib and selinexor via a clinical trial, which led to temporary improvement of leg lesions; when the lesions returned, biopsy was performed with the same histopathological result. Lenalidomide and rituximab were started, but without success, and disease spread to the central nervous system.
Another biopsy of the skin lesions again supported cutaneous MCL, with tumor cells rimming individual adipocytes.
Because of this atypical morphology, fluorescence in situ hybridization (FISH) was conducted, revealing t(11;14)(q13:32) positivity, thereby “confirming the diagnosis of cutaneous involvement by systemic MCL,” the investigators wrote.
Genomic sequencing revealed abnormalities of “ataxia-telangiectasia mutated, mechanistic target of rapamycin kinase (mTOR), BCL6 corepressor, and FAS-associated factor 1, as well as the expected mutation in IGH-CCND1, leading to cyclin D1 upregulation.”
Subsequent treatment was unsuccessful, and the patient died from his disease.
“The complex and central role that mTOR plays in adipose homeostasis may link our tumor to its preference to the adipose tissue, although further investigation is warranted regarding specific genomic alterations in lymphomas and the implications these mutations have in the involvement of tumor cells with cutaneous and adipose environments,” the investigators wrote.
The investigators did not report conflicts of interest.
SOURCE: Laggis C et al. 2019 Apr 8. doi:10.1111/cup.13471.
An atypical case of cutaneous mantle cell lymphoma (MCL) with histomorphological features mimicking subcutaneous panniculitis-like T-cell lymphoma (SPTCL) highlights a “potential pitfall,” according to investigators.
This unusual case stresses the importance of molecular cytogenetics and/or immunohistochemistry for panniculitis-type lymphomas, reported lead author Caroline Laggis, MD of the University of Utah, Salt Lake City, and colleagues.
“While morphologic features of SPTCL, specifically rimming of adipocytes by neoplastic lymphoid cells, have been documented in other types of lymphomas, this case is exceptional in that the morphologic features of SPTCL are showed in secondary cutaneous involvement by MCL,” the investigators wrote. Their report is in Journal of Cutaneous Pathology.
The patient was a 69-year-old man who presented with 2-year history of night sweats and fever of unknown origin, and, closer to presentation, weight loss and tender bumps under the skin of his pelvic region.
Subsequent computed tomography and excisional lymph node biopsy led to a diagnosis of MCL, with a Mantle Cell Lymphoma International Prognostic Index of 5, suggesting aggressive, intermediate-risk disease. Further imaging showed involvement of the nasopharynx, and cervical and mediastinal lymph nodes.
Bendamustine and rituximab chemotherapy was given unremarkably until the final cycle, at which point the patient presented with tender subcutaneous nodules on his lower legs. Histopathology from punch biopsies revealed “a dense infiltrate of monomorphic, mitotically active lymphoid cells with infiltration between the deep dermal collagen and the adipocytes in subcutaneous fat,” the investigators wrote, noting that the infiltrative cells were blastoid and 70% expressed cyclin D1, supporting cutaneous involvement of his systemic MCL.
Treatment was switched to ibrutinib and selinexor via a clinical trial, which led to temporary improvement of leg lesions; when the lesions returned, biopsy was performed with the same histopathological result. Lenalidomide and rituximab were started, but without success, and disease spread to the central nervous system.
Another biopsy of the skin lesions again supported cutaneous MCL, with tumor cells rimming individual adipocytes.
Because of this atypical morphology, fluorescence in situ hybridization (FISH) was conducted, revealing t(11;14)(q13:32) positivity, thereby “confirming the diagnosis of cutaneous involvement by systemic MCL,” the investigators wrote.
Genomic sequencing revealed abnormalities of “ataxia-telangiectasia mutated, mechanistic target of rapamycin kinase (mTOR), BCL6 corepressor, and FAS-associated factor 1, as well as the expected mutation in IGH-CCND1, leading to cyclin D1 upregulation.”
Subsequent treatment was unsuccessful, and the patient died from his disease.
“The complex and central role that mTOR plays in adipose homeostasis may link our tumor to its preference to the adipose tissue, although further investigation is warranted regarding specific genomic alterations in lymphomas and the implications these mutations have in the involvement of tumor cells with cutaneous and adipose environments,” the investigators wrote.
The investigators did not report conflicts of interest.
SOURCE: Laggis C et al. 2019 Apr 8. doi:10.1111/cup.13471.
FROM JOURNAL OF CUTANEOUS PATHOLOGY