Aggressive Lymphomas

Photo by © ASCO/Zach Boyden-Holmes 2018

CHICAGO—Ibrutinib combined with venetoclax is showing promising clinical activity in the frontline treatment of patients with chronic lymphocytic leukemia (CLL), according to investigators for the CAPTIVATE study.

In the first 30 patients, 77% of treatment-naïve patients had undetected minimal residual disease (MRD; <10^-4 cells) in the blood and 86% showed a similar response in the bone marrow.

The overall response rate (ORR) was 100% in 11 evaluable patients. The investigators reported this initial data at the 2018 Annual Meeting of the American Society of Clinical Oncology (abstract 7502).

“These early results show a highly active and safe treatment with 12 cycles of combined treatment with ibrutinib and venetoclax,” said William G. Wierda, MD, PhD, of the MD Anderson Cancer Center in Houston, Texas, who presented the findings at ASCO.

Ibrutinib, a Bruton-kinase inhibitor, has already been approved for the treatment of CLL and venetoclax, a Bcl-2 inhibitor, is currently used to treat relapsed del 17p CLL.

Venetoclax in combination with rituximab was recently approved by the US Food and Drug Administration to treat patients with CLL or small lymphocytic lymphoma whether or not patients have del 17p.

With complementary mechanisms of action and preclinical studies suggesting synergy with the combination, CAPTIVATE was designed to test the efficacy of the oral combination given for 12 cycles.

Study design

 CAPTIVATE (NCT02910583) is an ongoing phase 2 study that enrolled 164 patients with treatment-naïve CLL. Patients first received 3 cycles of ibrutinib monotherapy at the standard dose. This was intended to debulk the disease and reduce risk for venetoclax-associated tumor lysis syndrome (TLS).

Venetoclax 400 mg was initiated at cycle 4. After 12 cycles of the combination, patients with confirmed MRD negativity were randomized to receive ibrutinib with a placebo or to continue with the combination therapy.

In this initial report, Dr Wierda highlighted safety data for all 164 enrolled patients and efficacy data for the first 30 patients who had 6 cycles of combination therapy (MRD assessment cohort).

Dr Wierda also reported bone marrow data for the first 14 patients, who received a total of 12 cycles of the combination and represent the safety run-in cohort.

Ibrutinib and venetoclax show promising activity

 Median age of patients was 58 years; about 2/3 of patients had unmutated IGHV and 1/3 had a creatine clearance of <80 mL/min.

Of 164 patients, 95% remain on therapy, with discontinuations reported for adverse events; one patient had disease progression to Richter’s transformation.

For the MRD evaluation, all 30 patients had 6 months of combination therapy and continue on treatment.

As expected, lead-in with ibrutinib monotherapy debulked the disease.

Investigators observed a reduction in the proportion of patients at high risk for TLS (24% to 3%) and an increase in the proportion of patients at low risk for TLS (12% to 29%).

A similar picture emerged for debulking of lymph node disease. No patient developed clinical TLS.

Other adverse events were consistent with the safety profile of single-agent ibrutinib and venetoclax. No new safety signals were seen.

After 6 cycles of the combination, blood MRD negativity was reported in 77% of the patients in the MRD assessment cohort.

In the safety-run in cohort of 14 patients, blood MRD negativity was reported in 86% of patients after 12 cycles and 93% of patients after 15 cycles of the combination. In these patients, bone marrow MRD negativity was achieved in 86%.

After 12 cycles of combination therapy, the objective response rate was 100% for 11 of the 14 evaluable patients from the safety run-in cohort: 6 patients showed complete remission (CR) or CR with incomplete blood count recovery (CRi) for a CR/CRi of 55%. All patients had confirmed undetectable MRD.

Investigators considered these responses promising and an assessment of the full treatment plan and durability of response are awaited.

The study was sponsored by Pharmacyclics. 

Photo by © ASCO/Zach Boyden-Holmes 2018

CHICAGO—Ibrutinib combined with venetoclax is showing promising clinical activity in the frontline treatment of patients with chronic lymphocytic leukemia (CLL), according to investigators for the CAPTIVATE study.

In the first 30 patients, 77% of treatment-naïve patients had undetected minimal residual disease (MRD; <10^-4 cells) in the blood and 86% showed a similar response in the bone marrow.

The overall response rate (ORR) was 100% in 11 evaluable patients. The investigators reported this initial data at the 2018 Annual Meeting of the American Society of Clinical Oncology (abstract 7502).

“These early results show a highly active and safe treatment with 12 cycles of combined treatment with ibrutinib and venetoclax,” said William G. Wierda, MD, PhD, of the MD Anderson Cancer Center in Houston, Texas, who presented the findings at ASCO.

Ibrutinib, a Bruton-kinase inhibitor, has already been approved for the treatment of CLL and venetoclax, a Bcl-2 inhibitor, is currently used to treat relapsed del 17p CLL.

Venetoclax in combination with rituximab was recently approved by the US Food and Drug Administration to treat patients with CLL or small lymphocytic lymphoma whether or not patients have del 17p.

With complementary mechanisms of action and preclinical studies suggesting synergy with the combination, CAPTIVATE was designed to test the efficacy of the oral combination given for 12 cycles.

Study design

 CAPTIVATE (NCT02910583) is an ongoing phase 2 study that enrolled 164 patients with treatment-naïve CLL. Patients first received 3 cycles of ibrutinib monotherapy at the standard dose. This was intended to debulk the disease and reduce risk for venetoclax-associated tumor lysis syndrome (TLS).

Venetoclax 400 mg was initiated at cycle 4. After 12 cycles of the combination, patients with confirmed MRD negativity were randomized to receive ibrutinib with a placebo or to continue with the combination therapy.

In this initial report, Dr Wierda highlighted safety data for all 164 enrolled patients and efficacy data for the first 30 patients who had 6 cycles of combination therapy (MRD assessment cohort).

Dr Wierda also reported bone marrow data for the first 14 patients, who received a total of 12 cycles of the combination and represent the safety run-in cohort.

Ibrutinib and venetoclax show promising activity

 Median age of patients was 58 years; about 2/3 of patients had unmutated IGHV and 1/3 had a creatine clearance of <80 mL/min.

Of 164 patients, 95% remain on therapy, with discontinuations reported for adverse events; one patient had disease progression to Richter’s transformation.

For the MRD evaluation, all 30 patients had 6 months of combination therapy and continue on treatment.

As expected, lead-in with ibrutinib monotherapy debulked the disease.

Investigators observed a reduction in the proportion of patients at high risk for TLS (24% to 3%) and an increase in the proportion of patients at low risk for TLS (12% to 29%).

A similar picture emerged for debulking of lymph node disease. No patient developed clinical TLS.

Other adverse events were consistent with the safety profile of single-agent ibrutinib and venetoclax. No new safety signals were seen.

After 6 cycles of the combination, blood MRD negativity was reported in 77% of the patients in the MRD assessment cohort.

In the safety-run in cohort of 14 patients, blood MRD negativity was reported in 86% of patients after 12 cycles and 93% of patients after 15 cycles of the combination. In these patients, bone marrow MRD negativity was achieved in 86%.

After 12 cycles of combination therapy, the objective response rate was 100% for 11 of the 14 evaluable patients from the safety run-in cohort: 6 patients showed complete remission (CR) or CR with incomplete blood count recovery (CRi) for a CR/CRi of 55%. All patients had confirmed undetectable MRD.

Investigators considered these responses promising and an assessment of the full treatment plan and durability of response are awaited.

The study was sponsored by Pharmacyclics. 

Photo by © ASCO/Zach Boyden-Holmes 2018

CHICAGO—Ibrutinib combined with venetoclax is showing promising clinical activity in the frontline treatment of patients with chronic lymphocytic leukemia (CLL), according to investigators for the CAPTIVATE study.

In the first 30 patients, 77% of treatment-naïve patients had undetected minimal residual disease (MRD; <10^-4 cells) in the blood and 86% showed a similar response in the bone marrow.

The overall response rate (ORR) was 100% in 11 evaluable patients. The investigators reported this initial data at the 2018 Annual Meeting of the American Society of Clinical Oncology (abstract 7502).

“These early results show a highly active and safe treatment with 12 cycles of combined treatment with ibrutinib and venetoclax,” said William G. Wierda, MD, PhD, of the MD Anderson Cancer Center in Houston, Texas, who presented the findings at ASCO.

Ibrutinib, a Bruton-kinase inhibitor, has already been approved for the treatment of CLL and venetoclax, a Bcl-2 inhibitor, is currently used to treat relapsed del 17p CLL.

Venetoclax in combination with rituximab was recently approved by the US Food and Drug Administration to treat patients with CLL or small lymphocytic lymphoma whether or not patients have del 17p.

With complementary mechanisms of action and preclinical studies suggesting synergy with the combination, CAPTIVATE was designed to test the efficacy of the oral combination given for 12 cycles.

Study design

 CAPTIVATE (NCT02910583) is an ongoing phase 2 study that enrolled 164 patients with treatment-naïve CLL. Patients first received 3 cycles of ibrutinib monotherapy at the standard dose. This was intended to debulk the disease and reduce risk for venetoclax-associated tumor lysis syndrome (TLS).

Venetoclax 400 mg was initiated at cycle 4. After 12 cycles of the combination, patients with confirmed MRD negativity were randomized to receive ibrutinib with a placebo or to continue with the combination therapy.

In this initial report, Dr Wierda highlighted safety data for all 164 enrolled patients and efficacy data for the first 30 patients who had 6 cycles of combination therapy (MRD assessment cohort).

Dr Wierda also reported bone marrow data for the first 14 patients, who received a total of 12 cycles of the combination and represent the safety run-in cohort.

Ibrutinib and venetoclax show promising activity

 Median age of patients was 58 years; about 2/3 of patients had unmutated IGHV and 1/3 had a creatine clearance of <80 mL/min.

Of 164 patients, 95% remain on therapy, with discontinuations reported for adverse events; one patient had disease progression to Richter’s transformation.

For the MRD evaluation, all 30 patients had 6 months of combination therapy and continue on treatment.

As expected, lead-in with ibrutinib monotherapy debulked the disease.

Investigators observed a reduction in the proportion of patients at high risk for TLS (24% to 3%) and an increase in the proportion of patients at low risk for TLS (12% to 29%).

A similar picture emerged for debulking of lymph node disease. No patient developed clinical TLS.

Other adverse events were consistent with the safety profile of single-agent ibrutinib and venetoclax. No new safety signals were seen.

After 6 cycles of the combination, blood MRD negativity was reported in 77% of the patients in the MRD assessment cohort.

In the safety-run in cohort of 14 patients, blood MRD negativity was reported in 86% of patients after 12 cycles and 93% of patients after 15 cycles of the combination. In these patients, bone marrow MRD negativity was achieved in 86%.

After 12 cycles of combination therapy, the objective response rate was 100% for 11 of the 14 evaluable patients from the safety run-in cohort: 6 patients showed complete remission (CR) or CR with incomplete blood count recovery (CRi) for a CR/CRi of 55%. All patients had confirmed undetectable MRD.

Investigators considered these responses promising and an assessment of the full treatment plan and durability of response are awaited.

The study was sponsored by Pharmacyclics. 

©ASCO/Scott Morgan 2018

CHICAGO—A chemotherapy-free combination of lenalidomide plus rituximab shows similar efficacy and a different safety profile to chemotherapy plus rituximab (R-chemo) followed by rituximab maintenance in patients with previously untreated follicular lymphoma (FL).

According to investigators, the multicenter, international phase 3 RELEVANCE trial is the first to evaluate the chemo-free combination against the standard of care, R-chemo with rituximab maintenance.

“These results show that lenalidomide plus rituximab, a novel immunomodulatory approach, is a potential first-line option for patients with FL requiring treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Dr Fowler presented the results of the study at the 2018 ASCO Annual Meeting (abstract 7500).

The current standard of care in previously untreated symptomatic FL is immunochemotherapy induction followed by rituximab maintenance.

The immunomodulatory agent lenalidomide has complementary mechanisms with rituximab. Phase 2 studies of combined immunotherapy with lenalidomide and rituximab demonstrated 3-year progression-free survival (PFS) of 79%-81% in previously untreated FL, Dr Fowler said.

Phase 3 RELEVANCE trial (NCT01650701)

Investigators evaluated 1030 previously untreated grade 1-3a FL patients who required therapy.

Patients in the lenalidomide-rituximab group (n=513) received lenalidomide doses of 20 mg per day on days 2 to 22 and 28 for 6 to 12 cycles. Responders continued on therapy at 10 mg per day for a total of 18 cycles.

The rituximab dose was 375 mg/m² weekly in cycle 1 and day 1 in cycles 2 to 6 and continued in responders for 12 additional cycles.

Patients in the R-chemo arm (n=517) received the investigator’s choice of standard rituximab-CHOP, rituximab-bendamustine, or rituximab-CVP, followed by 12 cycles of rituximab.

Most patients (72%) in the R-chemo arm received R-CHOP.

Baseline characteristics were similar in both groups, Dr Fowler said.

Co-primary endpoints were complete remission/complete remission unconfirmed (CR/Cru) at 120 weeks and PFS.

Results

At a median follow-up of 37.9 months, the superiority for lenalidomide and rituximab over rituximab-chemotherapy was not established.

For the lenalidomide-rituximab patients, the CR/Cru was 48% and 3-year PFS was 77% as compared to 53% and 78%, respectively, for rituximab-chemotherapy patients, as assessed by an independent review committee.

Overall survival was 94% in both groups.

Safety

“Important differences in safety profiles were observed between the arms,” Dr Fowler said.

Rituximab-chemotherapy patients had more frequent neutropenia, febrile neutropenia, growth factor usage, nausea, vomiting, neuropathy, and alopecia.

Lenalidomide and rituximab showed more cutaneous reactions, tumor flare, and diarrhea.

Toxicity profiles differed, with higher grade 4 neutropenia (31% vs 8%) and febrile neutropenia (7% vs 2%) with rituximab-chemotherapy compared with lenalidomide-rituximab, respectively.

More patients experienced grade 3/4 cutaneous events (7% vs 1%) with lenalidomide-rituximab.

Second primary malignancies were slightly higher with rituximab-chemotherapy (10%) than with lenalidomide-rituximab (7%). Grade 5 adverse events were 1% in both groups.

About 70% of patients completed treatment in both groups.

“Lenalidomide and rituximab was not superior to rituximab-chemotherapy based on mature CR/Cru at 120 weeks and interim PFS,” Dr Fowler said. “Both treatments showed similar efficacy results. Treatment effects on PFS were consistent across pre-specified subgroups.”

Dr Fowler presented data as of May 31, 2017. Continued follow-up on PFS and OS is ongoing.

The study is sponsored by Celgene Corporation and the Lymphoma Academic Research Organisation (LYSARC). 

©ASCO/Scott Morgan 2018

CHICAGO—A chemotherapy-free combination of lenalidomide plus rituximab shows similar efficacy and a different safety profile to chemotherapy plus rituximab (R-chemo) followed by rituximab maintenance in patients with previously untreated follicular lymphoma (FL).

According to investigators, the multicenter, international phase 3 RELEVANCE trial is the first to evaluate the chemo-free combination against the standard of care, R-chemo with rituximab maintenance.

“These results show that lenalidomide plus rituximab, a novel immunomodulatory approach, is a potential first-line option for patients with FL requiring treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Dr Fowler presented the results of the study at the 2018 ASCO Annual Meeting (abstract 7500).

The current standard of care in previously untreated symptomatic FL is immunochemotherapy induction followed by rituximab maintenance.

The immunomodulatory agent lenalidomide has complementary mechanisms with rituximab. Phase 2 studies of combined immunotherapy with lenalidomide and rituximab demonstrated 3-year progression-free survival (PFS) of 79%-81% in previously untreated FL, Dr Fowler said.

Phase 3 RELEVANCE trial (NCT01650701)

Investigators evaluated 1030 previously untreated grade 1-3a FL patients who required therapy.

Patients in the lenalidomide-rituximab group (n=513) received lenalidomide doses of 20 mg per day on days 2 to 22 and 28 for 6 to 12 cycles. Responders continued on therapy at 10 mg per day for a total of 18 cycles.

The rituximab dose was 375 mg/m² weekly in cycle 1 and day 1 in cycles 2 to 6 and continued in responders for 12 additional cycles.

Patients in the R-chemo arm (n=517) received the investigator’s choice of standard rituximab-CHOP, rituximab-bendamustine, or rituximab-CVP, followed by 12 cycles of rituximab.

Most patients (72%) in the R-chemo arm received R-CHOP.

Baseline characteristics were similar in both groups, Dr Fowler said.

Co-primary endpoints were complete remission/complete remission unconfirmed (CR/Cru) at 120 weeks and PFS.

Results

At a median follow-up of 37.9 months, the superiority for lenalidomide and rituximab over rituximab-chemotherapy was not established.

For the lenalidomide-rituximab patients, the CR/Cru was 48% and 3-year PFS was 77% as compared to 53% and 78%, respectively, for rituximab-chemotherapy patients, as assessed by an independent review committee.

Overall survival was 94% in both groups.

Safety

“Important differences in safety profiles were observed between the arms,” Dr Fowler said.

Rituximab-chemotherapy patients had more frequent neutropenia, febrile neutropenia, growth factor usage, nausea, vomiting, neuropathy, and alopecia.

Lenalidomide and rituximab showed more cutaneous reactions, tumor flare, and diarrhea.

Toxicity profiles differed, with higher grade 4 neutropenia (31% vs 8%) and febrile neutropenia (7% vs 2%) with rituximab-chemotherapy compared with lenalidomide-rituximab, respectively.

More patients experienced grade 3/4 cutaneous events (7% vs 1%) with lenalidomide-rituximab.

Second primary malignancies were slightly higher with rituximab-chemotherapy (10%) than with lenalidomide-rituximab (7%). Grade 5 adverse events were 1% in both groups.

About 70% of patients completed treatment in both groups.

“Lenalidomide and rituximab was not superior to rituximab-chemotherapy based on mature CR/Cru at 120 weeks and interim PFS,” Dr Fowler said. “Both treatments showed similar efficacy results. Treatment effects on PFS were consistent across pre-specified subgroups.”

Dr Fowler presented data as of May 31, 2017. Continued follow-up on PFS and OS is ongoing.

The study is sponsored by Celgene Corporation and the Lymphoma Academic Research Organisation (LYSARC). 

©ASCO/Scott Morgan 2018

CHICAGO—A chemotherapy-free combination of lenalidomide plus rituximab shows similar efficacy and a different safety profile to chemotherapy plus rituximab (R-chemo) followed by rituximab maintenance in patients with previously untreated follicular lymphoma (FL).

According to investigators, the multicenter, international phase 3 RELEVANCE trial is the first to evaluate the chemo-free combination against the standard of care, R-chemo with rituximab maintenance.

“These results show that lenalidomide plus rituximab, a novel immunomodulatory approach, is a potential first-line option for patients with FL requiring treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Dr Fowler presented the results of the study at the 2018 ASCO Annual Meeting (abstract 7500).

The current standard of care in previously untreated symptomatic FL is immunochemotherapy induction followed by rituximab maintenance.

The immunomodulatory agent lenalidomide has complementary mechanisms with rituximab. Phase 2 studies of combined immunotherapy with lenalidomide and rituximab demonstrated 3-year progression-free survival (PFS) of 79%-81% in previously untreated FL, Dr Fowler said.

Phase 3 RELEVANCE trial (NCT01650701)

Investigators evaluated 1030 previously untreated grade 1-3a FL patients who required therapy.

Patients in the lenalidomide-rituximab group (n=513) received lenalidomide doses of 20 mg per day on days 2 to 22 and 28 for 6 to 12 cycles. Responders continued on therapy at 10 mg per day for a total of 18 cycles.

The rituximab dose was 375 mg/m² weekly in cycle 1 and day 1 in cycles 2 to 6 and continued in responders for 12 additional cycles.

Patients in the R-chemo arm (n=517) received the investigator’s choice of standard rituximab-CHOP, rituximab-bendamustine, or rituximab-CVP, followed by 12 cycles of rituximab.

Most patients (72%) in the R-chemo arm received R-CHOP.

Baseline characteristics were similar in both groups, Dr Fowler said.

Co-primary endpoints were complete remission/complete remission unconfirmed (CR/Cru) at 120 weeks and PFS.

Results

At a median follow-up of 37.9 months, the superiority for lenalidomide and rituximab over rituximab-chemotherapy was not established.

For the lenalidomide-rituximab patients, the CR/Cru was 48% and 3-year PFS was 77% as compared to 53% and 78%, respectively, for rituximab-chemotherapy patients, as assessed by an independent review committee.

Overall survival was 94% in both groups.

Safety

“Important differences in safety profiles were observed between the arms,” Dr Fowler said.

Rituximab-chemotherapy patients had more frequent neutropenia, febrile neutropenia, growth factor usage, nausea, vomiting, neuropathy, and alopecia.

Lenalidomide and rituximab showed more cutaneous reactions, tumor flare, and diarrhea.

Toxicity profiles differed, with higher grade 4 neutropenia (31% vs 8%) and febrile neutropenia (7% vs 2%) with rituximab-chemotherapy compared with lenalidomide-rituximab, respectively.

More patients experienced grade 3/4 cutaneous events (7% vs 1%) with lenalidomide-rituximab.

Second primary malignancies were slightly higher with rituximab-chemotherapy (10%) than with lenalidomide-rituximab (7%). Grade 5 adverse events were 1% in both groups.

About 70% of patients completed treatment in both groups.

“Lenalidomide and rituximab was not superior to rituximab-chemotherapy based on mature CR/Cru at 120 weeks and interim PFS,” Dr Fowler said. “Both treatments showed similar efficacy results. Treatment effects on PFS were consistent across pre-specified subgroups.”

Dr Fowler presented data as of May 31, 2017. Continued follow-up on PFS and OS is ongoing.

The study is sponsored by Celgene Corporation and the Lymphoma Academic Research Organisation (LYSARC). 

Photo courtesy of Abbvie

The US Food and Drug Administration (FDA) has approved venetoclax tablets (Venclexta ®) in combination with rituximab to treat patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received 1 prior therapy.

The combination is approved for patients with or without deletion of 17p (del 17p).

The FDA based its approval on the phase 3 MURANO trial, in which venetoclax in combination with rituximab (VEN+R) significantly improved progression-free survival (PFS) in relapsed or refractory CLL patients compared to the chemoimmunotherapy regimen of bendamustine plus rituximab(B+R).

This approval, according to the drug’s developers, makes venetoclax plus rituximab the first oral-based, chemotherapy-free combination with a fixed treatment duration for CLL.

The FDA has also converted venetoclax's accelerated approval to a full approval. The drug was previously granted accelerated approval as a single agent for the treatment of people with CLL with 17p deletion.

Venetoclax is being developed by AbbVie and Roche and jointly commercialized by AbbVie and Genentech in the US and by AbbVie outside the US.

Phase 3 MURANO trial (NCT02005471)

The multicenter, open-label trial randomized 389 patients to VEN+R (194 patients) or B+R (195 patients). Median age of the patients was 65 years (range, 22 – 85).

Patients in the VEN+R arm completed a 5-week ramp-up of venetoclax followed by venetoclax 400 mg once daily for 24 months measured from the rituximab start date.

Tumor lysis syndrome (TLS), caused by a rapid reduction in tumor volume, is an identified risk with venetoclax treatment. The dose ramp-up was intended to mitigate this risk.

Rituximab was initiated after venetoclax ramp-up and given for 6 cycles (375 mg/m² intravenously on cycle 1 day 1 and 500 mg/m² intravenously on day 1 of cycles 2-6, with a 28-day cycle length).

Patients in the B+R arm received 6 cycles of B+R (bendamustine 70 mg/m² on days 1 and 2 of each 28-day cycle and rituximab at the above described dose and schedule).

Efficacy was based on PFS as assessed by an independent review committee.

After a median follow-up of 23 months, the median PFS was not reached in the VEN+R arm and was 18.1 months in the B+R arm (P<0.0001).

The overall response rate was 92% for patients treated with VEN+R compared to 72% for those treated with B+R.

Safety

The most common adverse events (AEs) in the VEN+R arms that occurred in 20% or more patients were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), cough (22%), and nausea (21%).

Grade 3 or 4 neutropenia developed in 64% of patients, and grade 4 neutropenia in 31%.

Serious adverse events (SAEs) developed in 46% of patients and serious infections in 21%, consisting most frequently of pneumonia (9%).

The incidence of TLS was 3%, occurring in 6 of  194 patients.

In the VEN+R arm, discontinuations due to any AEs occurred in 16% of patients, dose reductions in 15%, and dose interruptions in 71%.

Neutropenia led to dose interruptions in 46% of patients and discontinuations in 3%. Thrombocytopenia led to discontinuations in 3% of patients.

Fatal AEs that occurred in the absence of disease progression and within 30 days of the last VEN+R treatment and/or 90 days of the last rituximab infusion were reported in 2% (4/194) of patients.

In the B+R arm, AEs led to treatment discontinuations in 10% of patients, dose reductions in 15%, and dose interruptions in 40 %.

Investigators previously reported data from the phase 3 MURANO study as a late-breaking abstract at the 2017 ASH Annual Meeting and published the findings in NEJM.

John Seymour, MBBS, PhD, lead investigator of the MURANO study, said in the corporate release, the approval "validates the results seen in the phase 3 trial, including the significant improvement in progression-free survival over a standard of care comparator arm."

"Progression-free survival is considered a gold standard for demonstrating clinical benefit in oncology," he added.

Full prescribing information for venetoclax is available here. 

Photo courtesy of Abbvie

The US Food and Drug Administration (FDA) has approved venetoclax tablets (Venclexta ®) in combination with rituximab to treat patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received 1 prior therapy.

The combination is approved for patients with or without deletion of 17p (del 17p).

The FDA based its approval on the phase 3 MURANO trial, in which venetoclax in combination with rituximab (VEN+R) significantly improved progression-free survival (PFS) in relapsed or refractory CLL patients compared to the chemoimmunotherapy regimen of bendamustine plus rituximab(B+R).

This approval, according to the drug’s developers, makes venetoclax plus rituximab the first oral-based, chemotherapy-free combination with a fixed treatment duration for CLL.

The FDA has also converted venetoclax's accelerated approval to a full approval. The drug was previously granted accelerated approval as a single agent for the treatment of people with CLL with 17p deletion.

Venetoclax is being developed by AbbVie and Roche and jointly commercialized by AbbVie and Genentech in the US and by AbbVie outside the US.

Phase 3 MURANO trial (NCT02005471)

The multicenter, open-label trial randomized 389 patients to VEN+R (194 patients) or B+R (195 patients). Median age of the patients was 65 years (range, 22 – 85).

Patients in the VEN+R arm completed a 5-week ramp-up of venetoclax followed by venetoclax 400 mg once daily for 24 months measured from the rituximab start date.

Tumor lysis syndrome (TLS), caused by a rapid reduction in tumor volume, is an identified risk with venetoclax treatment. The dose ramp-up was intended to mitigate this risk.

Rituximab was initiated after venetoclax ramp-up and given for 6 cycles (375 mg/m² intravenously on cycle 1 day 1 and 500 mg/m² intravenously on day 1 of cycles 2-6, with a 28-day cycle length).

Patients in the B+R arm received 6 cycles of B+R (bendamustine 70 mg/m² on days 1 and 2 of each 28-day cycle and rituximab at the above described dose and schedule).

Efficacy was based on PFS as assessed by an independent review committee.

After a median follow-up of 23 months, the median PFS was not reached in the VEN+R arm and was 18.1 months in the B+R arm (P<0.0001).

The overall response rate was 92% for patients treated with VEN+R compared to 72% for those treated with B+R.

Safety

The most common adverse events (AEs) in the VEN+R arms that occurred in 20% or more patients were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), cough (22%), and nausea (21%).

Grade 3 or 4 neutropenia developed in 64% of patients, and grade 4 neutropenia in 31%.

Serious adverse events (SAEs) developed in 46% of patients and serious infections in 21%, consisting most frequently of pneumonia (9%).

The incidence of TLS was 3%, occurring in 6 of  194 patients.

In the VEN+R arm, discontinuations due to any AEs occurred in 16% of patients, dose reductions in 15%, and dose interruptions in 71%.

Neutropenia led to dose interruptions in 46% of patients and discontinuations in 3%. Thrombocytopenia led to discontinuations in 3% of patients.

Fatal AEs that occurred in the absence of disease progression and within 30 days of the last VEN+R treatment and/or 90 days of the last rituximab infusion were reported in 2% (4/194) of patients.

In the B+R arm, AEs led to treatment discontinuations in 10% of patients, dose reductions in 15%, and dose interruptions in 40 %.

Investigators previously reported data from the phase 3 MURANO study as a late-breaking abstract at the 2017 ASH Annual Meeting and published the findings in NEJM.

John Seymour, MBBS, PhD, lead investigator of the MURANO study, said in the corporate release, the approval "validates the results seen in the phase 3 trial, including the significant improvement in progression-free survival over a standard of care comparator arm."

"Progression-free survival is considered a gold standard for demonstrating clinical benefit in oncology," he added.

Full prescribing information for venetoclax is available here. 

Photo courtesy of Abbvie

The US Food and Drug Administration (FDA) has approved venetoclax tablets (Venclexta ®) in combination with rituximab to treat patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received 1 prior therapy.

The combination is approved for patients with or without deletion of 17p (del 17p).

The FDA based its approval on the phase 3 MURANO trial, in which venetoclax in combination with rituximab (VEN+R) significantly improved progression-free survival (PFS) in relapsed or refractory CLL patients compared to the chemoimmunotherapy regimen of bendamustine plus rituximab(B+R).

This approval, according to the drug’s developers, makes venetoclax plus rituximab the first oral-based, chemotherapy-free combination with a fixed treatment duration for CLL.

The FDA has also converted venetoclax's accelerated approval to a full approval. The drug was previously granted accelerated approval as a single agent for the treatment of people with CLL with 17p deletion.

Venetoclax is being developed by AbbVie and Roche and jointly commercialized by AbbVie and Genentech in the US and by AbbVie outside the US.

Phase 3 MURANO trial (NCT02005471)

The multicenter, open-label trial randomized 389 patients to VEN+R (194 patients) or B+R (195 patients). Median age of the patients was 65 years (range, 22 – 85).

Patients in the VEN+R arm completed a 5-week ramp-up of venetoclax followed by venetoclax 400 mg once daily for 24 months measured from the rituximab start date.

Tumor lysis syndrome (TLS), caused by a rapid reduction in tumor volume, is an identified risk with venetoclax treatment. The dose ramp-up was intended to mitigate this risk.

Rituximab was initiated after venetoclax ramp-up and given for 6 cycles (375 mg/m² intravenously on cycle 1 day 1 and 500 mg/m² intravenously on day 1 of cycles 2-6, with a 28-day cycle length).

Patients in the B+R arm received 6 cycles of B+R (bendamustine 70 mg/m² on days 1 and 2 of each 28-day cycle and rituximab at the above described dose and schedule).

Efficacy was based on PFS as assessed by an independent review committee.

After a median follow-up of 23 months, the median PFS was not reached in the VEN+R arm and was 18.1 months in the B+R arm (P<0.0001).

The overall response rate was 92% for patients treated with VEN+R compared to 72% for those treated with B+R.

Safety

The most common adverse events (AEs) in the VEN+R arms that occurred in 20% or more patients were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), cough (22%), and nausea (21%).

Grade 3 or 4 neutropenia developed in 64% of patients, and grade 4 neutropenia in 31%.

Serious adverse events (SAEs) developed in 46% of patients and serious infections in 21%, consisting most frequently of pneumonia (9%).

The incidence of TLS was 3%, occurring in 6 of  194 patients.

In the VEN+R arm, discontinuations due to any AEs occurred in 16% of patients, dose reductions in 15%, and dose interruptions in 71%.

Neutropenia led to dose interruptions in 46% of patients and discontinuations in 3%. Thrombocytopenia led to discontinuations in 3% of patients.

Fatal AEs that occurred in the absence of disease progression and within 30 days of the last VEN+R treatment and/or 90 days of the last rituximab infusion were reported in 2% (4/194) of patients.

In the B+R arm, AEs led to treatment discontinuations in 10% of patients, dose reductions in 15%, and dose interruptions in 40 %.

Investigators previously reported data from the phase 3 MURANO study as a late-breaking abstract at the 2017 ASH Annual Meeting and published the findings in NEJM.

John Seymour, MBBS, PhD, lead investigator of the MURANO study, said in the corporate release, the approval "validates the results seen in the phase 3 trial, including the significant improvement in progression-free survival over a standard of care comparator arm."

"Progression-free survival is considered a gold standard for demonstrating clinical benefit in oncology," he added.

Full prescribing information for venetoclax is available here. 

Attendees at ASCO 2018 ©ASCO/Zach Boyden-Holmes 2018

CHICAGO—Polatuzumab vedotin, when added to bendamustine (B) and rituximab (R), significantly improved response and survival rates in a cohort of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a phase 2 study.

By contrast, there were no such improvements in a cohort of follicular lymphoma (FL) patients, at least in short-term follow-up, investigator Laurie Helen Sehn, MD, of the BC Cancer Agency in Vancouver, Canada, said at the 2018 ASCO Annual Meeting.

However, the improvement in overall survival in DLBCL patients is “remarkable,” Dr Sehn affirmed in an oral presentation (abstract 7507).

“Based on these encouraging results, polatuzumab vedotin has received breakthrough therapy designation and priority medicines designation by the FDA and EMA for patients with relapsed or refractory DLBCL,” she said.

Polatuzumab-BR study (NCT02257567)

The study by Dr Sehn and colleagues included a cohort of 80 DLBCL patients randomized to BR or polatuzumab-BR for 6 planned 21-day cycles.

Investigators randomized another cohort of 80 FL patients to BR or polatuzumab-BR for 6 planned 28-day cycles.

The primary endpoint was complete response (CR) assessed by fluorodeoxyglucose positron emission tomography (FDG-PET) at 6 to 8 weeks after the end of treatment.

DLBCL patients

A total of 40% of polatuzumab-BR-treated DLBCL patients achieved CR at the end of treatment, versus 15% of BR-treated patients (P=0.012).

That CR improvement translated into a significantly higher progression-free survival (PFS) (6.7 months for polatuzumab-BR vs 2.0 months for BR, P<0.0001) and overall survival (11.8 months versus 4.7 months, P=0.0008), according to Dr Sehn.

The FDG-PET CR rates were higher in the polatuzumab-BR arm regardless of the number of prior lines of treatment for DLBCL, and regardless of relapsed versus refractory status, Dr. Sehn added.

FL patients

By contrast, in the FL cohort, the FDG-PET CR rate was high for both arms, at 69% for polatuzumab-BR and 63% for BR.

And there was no significant difference in progression-free survival (P=0.58) with “relatively short-term follow-up,” she said.

Adverse events

The most common grades 3 – 5 adverse events for both DLBCL and FL patients were higher in the polatuzumab-BR arm than the BR arm and included cytopenias, febrile neutropenia, and infections.

Serious AEs were also higher in the polatuzumab-BR arm and included febrile neutropenia for both FL and DLBCL patients and infection for FL patients.

Five percent of FL patients and 18% of DLBCL had a grade 5 event.

Commentary

Whether polatuzumab vedotin will change treatment paradigms for DLBCL patients may be answered by the ongoing POLARIX study, according to Alison Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, NY.

The randomized phase 3 POLARIX study (abstract TPS7589) is comparing polatuzumab plus R-CHP to R-CHOP in patients with previously untreated DLBCL.

“Certainly, there are patients who do very well with R-CHOP chemotherapy alone, and so we need to learn whether this is necessary for all patients, or only the high-risk patients,” Dr Moskowitz said in a talk at ASCO commenting on the results of the polatuzumab-BR study.

Hoffman-LaRoche is the sponsor of the study. 

Attendees at ASCO 2018 ©ASCO/Zach Boyden-Holmes 2018

CHICAGO—Polatuzumab vedotin, when added to bendamustine (B) and rituximab (R), significantly improved response and survival rates in a cohort of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a phase 2 study.

By contrast, there were no such improvements in a cohort of follicular lymphoma (FL) patients, at least in short-term follow-up, investigator Laurie Helen Sehn, MD, of the BC Cancer Agency in Vancouver, Canada, said at the 2018 ASCO Annual Meeting.

However, the improvement in overall survival in DLBCL patients is “remarkable,” Dr Sehn affirmed in an oral presentation (abstract 7507).

“Based on these encouraging results, polatuzumab vedotin has received breakthrough therapy designation and priority medicines designation by the FDA and EMA for patients with relapsed or refractory DLBCL,” she said.

Polatuzumab-BR study (NCT02257567)

The study by Dr Sehn and colleagues included a cohort of 80 DLBCL patients randomized to BR or polatuzumab-BR for 6 planned 21-day cycles.

Investigators randomized another cohort of 80 FL patients to BR or polatuzumab-BR for 6 planned 28-day cycles.

The primary endpoint was complete response (CR) assessed by fluorodeoxyglucose positron emission tomography (FDG-PET) at 6 to 8 weeks after the end of treatment.

DLBCL patients

A total of 40% of polatuzumab-BR-treated DLBCL patients achieved CR at the end of treatment, versus 15% of BR-treated patients (P=0.012).

That CR improvement translated into a significantly higher progression-free survival (PFS) (6.7 months for polatuzumab-BR vs 2.0 months for BR, P<0.0001) and overall survival (11.8 months versus 4.7 months, P=0.0008), according to Dr Sehn.

The FDG-PET CR rates were higher in the polatuzumab-BR arm regardless of the number of prior lines of treatment for DLBCL, and regardless of relapsed versus refractory status, Dr. Sehn added.

FL patients

By contrast, in the FL cohort, the FDG-PET CR rate was high for both arms, at 69% for polatuzumab-BR and 63% for BR.

And there was no significant difference in progression-free survival (P=0.58) with “relatively short-term follow-up,” she said.

Adverse events

The most common grades 3 – 5 adverse events for both DLBCL and FL patients were higher in the polatuzumab-BR arm than the BR arm and included cytopenias, febrile neutropenia, and infections.

Serious AEs were also higher in the polatuzumab-BR arm and included febrile neutropenia for both FL and DLBCL patients and infection for FL patients.

Five percent of FL patients and 18% of DLBCL had a grade 5 event.

Commentary

Whether polatuzumab vedotin will change treatment paradigms for DLBCL patients may be answered by the ongoing POLARIX study, according to Alison Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, NY.

The randomized phase 3 POLARIX study (abstract TPS7589) is comparing polatuzumab plus R-CHP to R-CHOP in patients with previously untreated DLBCL.

“Certainly, there are patients who do very well with R-CHOP chemotherapy alone, and so we need to learn whether this is necessary for all patients, or only the high-risk patients,” Dr Moskowitz said in a talk at ASCO commenting on the results of the polatuzumab-BR study.

Hoffman-LaRoche is the sponsor of the study. 

Attendees at ASCO 2018 ©ASCO/Zach Boyden-Holmes 2018

CHICAGO—Polatuzumab vedotin, when added to bendamustine (B) and rituximab (R), significantly improved response and survival rates in a cohort of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a phase 2 study.

By contrast, there were no such improvements in a cohort of follicular lymphoma (FL) patients, at least in short-term follow-up, investigator Laurie Helen Sehn, MD, of the BC Cancer Agency in Vancouver, Canada, said at the 2018 ASCO Annual Meeting.

However, the improvement in overall survival in DLBCL patients is “remarkable,” Dr Sehn affirmed in an oral presentation (abstract 7507).

“Based on these encouraging results, polatuzumab vedotin has received breakthrough therapy designation and priority medicines designation by the FDA and EMA for patients with relapsed or refractory DLBCL,” she said.

Polatuzumab-BR study (NCT02257567)

The study by Dr Sehn and colleagues included a cohort of 80 DLBCL patients randomized to BR or polatuzumab-BR for 6 planned 21-day cycles.

Investigators randomized another cohort of 80 FL patients to BR or polatuzumab-BR for 6 planned 28-day cycles.

The primary endpoint was complete response (CR) assessed by fluorodeoxyglucose positron emission tomography (FDG-PET) at 6 to 8 weeks after the end of treatment.

DLBCL patients

A total of 40% of polatuzumab-BR-treated DLBCL patients achieved CR at the end of treatment, versus 15% of BR-treated patients (P=0.012).

That CR improvement translated into a significantly higher progression-free survival (PFS) (6.7 months for polatuzumab-BR vs 2.0 months for BR, P<0.0001) and overall survival (11.8 months versus 4.7 months, P=0.0008), according to Dr Sehn.

The FDG-PET CR rates were higher in the polatuzumab-BR arm regardless of the number of prior lines of treatment for DLBCL, and regardless of relapsed versus refractory status, Dr. Sehn added.

FL patients

By contrast, in the FL cohort, the FDG-PET CR rate was high for both arms, at 69% for polatuzumab-BR and 63% for BR.

And there was no significant difference in progression-free survival (P=0.58) with “relatively short-term follow-up,” she said.

Adverse events

The most common grades 3 – 5 adverse events for both DLBCL and FL patients were higher in the polatuzumab-BR arm than the BR arm and included cytopenias, febrile neutropenia, and infections.

Serious AEs were also higher in the polatuzumab-BR arm and included febrile neutropenia for both FL and DLBCL patients and infection for FL patients.

Five percent of FL patients and 18% of DLBCL had a grade 5 event.

Commentary

Whether polatuzumab vedotin will change treatment paradigms for DLBCL patients may be answered by the ongoing POLARIX study, according to Alison Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, NY.

The randomized phase 3 POLARIX study (abstract TPS7589) is comparing polatuzumab plus R-CHP to R-CHOP in patients with previously untreated DLBCL.

“Certainly, there are patients who do very well with R-CHOP chemotherapy alone, and so we need to learn whether this is necessary for all patients, or only the high-risk patients,” Dr Moskowitz said in a talk at ASCO commenting on the results of the polatuzumab-BR study.

Hoffman-LaRoche is the sponsor of the study. 

CHICAGO – Lenalidomide plus rituximab (R²) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.

RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.

Response and progression-free survival (PFS) results were similar for patients who received R² followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.

“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.

But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.

R² had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R² can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.

The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.

SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.

CHICAGO – Lenalidomide plus rituximab (R²) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.

RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.

Response and progression-free survival (PFS) results were similar for patients who received R² followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.

“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.

But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.

R² had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R² can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.

The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.

SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.

CHICAGO – Lenalidomide plus rituximab (R²) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.

RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.

Response and progression-free survival (PFS) results were similar for patients who received R² followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.

“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.

But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.

R² had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R² can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.

The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.

SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.

CHICAGO – A first-in-class antibody targeting the macrophage checkpoint CD47 is a promising novel immunotherapy in non-Hodgkin lymphoma, according to Ranjana H. Advani, MD, of Stanford (Calif.) Cancer Institute.

Treatment with Hu5F9-G4 (5F9), an antibody designed to overcome the “don’t eat me” signal associated with CD47, produced “encouraging” antitumor activity in a phase 1b study of 22 patients, Dr. Advani said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

“5F9 was well tolerated in combination with rituximab, with no maximum tolerated dose achieved,” said Dr. Advani, noting that there were complete remissions in 43% of the refractory follicular lymphoma patients and 33% of refractory diffuse large B-cell lymphoma patients in the phase 1b/2 study.

The antibody has an on-target anemia effect that occurs upon administration, but that was mitigated considerably by a priming and maintenance dosing approach, she added.

The study has demonstrated “excellent” response rates in a highly refractory patient population, said Caron A. Jacobson, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston. “Targeting CD47 ... really helps to shift the balance from ‘don’t eat me’ to ‘eat me,’ ” Dr. Jacobson said at the meeting.

“Importantly, we saw very little toxicity in the study, with very few grade 4 adverse events and no immune-related adverse events,” she added.

Most adverse events were grade 1 or 2, with the most common being the expected on-target anemia associated with 5F9. Using an initial priming dose of 5F9 results in a “temporary and mild decline” in hemoglobin due to clearance of aged red blood cells, Dr. Advani said.

SOURCE: Advani RH et al. ASCO 2018, abstract 7504.

CHICAGO – A first-in-class antibody targeting the macrophage checkpoint CD47 is a promising novel immunotherapy in non-Hodgkin lymphoma, according to Ranjana H. Advani, MD, of Stanford (Calif.) Cancer Institute.

Treatment with Hu5F9-G4 (5F9), an antibody designed to overcome the “don’t eat me” signal associated with CD47, produced “encouraging” antitumor activity in a phase 1b study of 22 patients, Dr. Advani said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

“5F9 was well tolerated in combination with rituximab, with no maximum tolerated dose achieved,” said Dr. Advani, noting that there were complete remissions in 43% of the refractory follicular lymphoma patients and 33% of refractory diffuse large B-cell lymphoma patients in the phase 1b/2 study.

The antibody has an on-target anemia effect that occurs upon administration, but that was mitigated considerably by a priming and maintenance dosing approach, she added.

The study has demonstrated “excellent” response rates in a highly refractory patient population, said Caron A. Jacobson, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston. “Targeting CD47 ... really helps to shift the balance from ‘don’t eat me’ to ‘eat me,’ ” Dr. Jacobson said at the meeting.

“Importantly, we saw very little toxicity in the study, with very few grade 4 adverse events and no immune-related adverse events,” she added.

Most adverse events were grade 1 or 2, with the most common being the expected on-target anemia associated with 5F9. Using an initial priming dose of 5F9 results in a “temporary and mild decline” in hemoglobin due to clearance of aged red blood cells, Dr. Advani said.

SOURCE: Advani RH et al. ASCO 2018, abstract 7504.

CHICAGO – A first-in-class antibody targeting the macrophage checkpoint CD47 is a promising novel immunotherapy in non-Hodgkin lymphoma, according to Ranjana H. Advani, MD, of Stanford (Calif.) Cancer Institute.

Treatment with Hu5F9-G4 (5F9), an antibody designed to overcome the “don’t eat me” signal associated with CD47, produced “encouraging” antitumor activity in a phase 1b study of 22 patients, Dr. Advani said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

“5F9 was well tolerated in combination with rituximab, with no maximum tolerated dose achieved,” said Dr. Advani, noting that there were complete remissions in 43% of the refractory follicular lymphoma patients and 33% of refractory diffuse large B-cell lymphoma patients in the phase 1b/2 study.

The antibody has an on-target anemia effect that occurs upon administration, but that was mitigated considerably by a priming and maintenance dosing approach, she added.

The study has demonstrated “excellent” response rates in a highly refractory patient population, said Caron A. Jacobson, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston. “Targeting CD47 ... really helps to shift the balance from ‘don’t eat me’ to ‘eat me,’ ” Dr. Jacobson said at the meeting.

“Importantly, we saw very little toxicity in the study, with very few grade 4 adverse events and no immune-related adverse events,” she added.

Most adverse events were grade 1 or 2, with the most common being the expected on-target anemia associated with 5F9. Using an initial priming dose of 5F9 results in a “temporary and mild decline” in hemoglobin due to clearance of aged red blood cells, Dr. Advani said.

SOURCE: Advani RH et al. ASCO 2018, abstract 7504.

©ASCO/Rodney White 2018

CHICAGO—Acalabrutinib monotherapy was highly effective in Waldenström’s macroglobulinemia (WM) in a phase 2 study, investigator Roger Owen, MD, reported at the 2018 ASCO Annual Meeting.

The BTK inhibitor was effective in both treatment-naïve and relapsed/refractory patients, with overall response rates for both groups in excess of 90%, and “amazing” major response rates—partial response or better—of approximately 80%, Dr Owen said.

Dr Owen, of the St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust in Leeds, UK, reported the findings as abstract 7501.*

Durations of response were excellent, according to Dr Owen, who also reported 2-year progression-free survival of 90% in treatment-naïve patients and 82% in relapsed/refractory patients.

The safety profile was favorable, with most adverse events of low grade, and a very limited number of dropouts due to adverse events, according to the investigator.

“I think this study clearly demonstrates the highly effective nature of acalabrutinib in Waldenström’s macroglobulinemia,” Dr Owen stated.

 Acalabrutinib is a selective BTK inhibitor with minimal off-target activity, he said. The BTK inhibitor ibrutinib also has demonstrated activity in Waldenström’s, but has been associated with toxicities such as atrial fibrillation and bleeding, he noted.

In this phase 2 acalabrutinib study (NCT02180724), which included 14 treatment-naïve and 92 relapsed/refractory patients, atrial fibrillation occurred in 5 patients. However, 4 of those cases were grade 1-2, and only one was grade 3, according to Dr Owen.

Investigators observed grade 3 hypertension in 3 relapsed/refractory patients.

Bleeding events occurred in more than half of patients, though only 3 of those events were grade 3, and no patient discontinued treatment due to a bleeding episode.

These efficacy results are “impressive,” and the fact that very few cardiac events were seen is important, said Bruce D. Cheson, MD, of Georgetown University Medical Center in Washington, DC.

Dr Cheson commented on the acalabrutinib results in his presentation during ASCO on non-chemotherapy treatments for lymphoid malignancies.

 “One can construct a non-chemo algorithm now for Waldenström’s, for patients who are MYD88 mutated, which is more than 90% of patients,” he said. “Right now ibrutinib, and perhaps in the future acalabrutinib, can be the initial therapy with or without rituximab based on the results of ongoing trials.”

However, single non-chemotherapy agents will not be sufficient to achieve cure of lymphoid malignancies, Dr Cheson added.

“We need to carefully develop rational combinations, identifying biomarkers for response, for resistance, for toxicity,” he said.

The study was sponsored by Acerta Pharma BV. 

*Data presented at the meeting differ from the abstract.

©ASCO/Rodney White 2018

CHICAGO—Acalabrutinib monotherapy was highly effective in Waldenström’s macroglobulinemia (WM) in a phase 2 study, investigator Roger Owen, MD, reported at the 2018 ASCO Annual Meeting.

The BTK inhibitor was effective in both treatment-naïve and relapsed/refractory patients, with overall response rates for both groups in excess of 90%, and “amazing” major response rates—partial response or better—of approximately 80%, Dr Owen said.

Dr Owen, of the St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust in Leeds, UK, reported the findings as abstract 7501.*

Durations of response were excellent, according to Dr Owen, who also reported 2-year progression-free survival of 90% in treatment-naïve patients and 82% in relapsed/refractory patients.

The safety profile was favorable, with most adverse events of low grade, and a very limited number of dropouts due to adverse events, according to the investigator.

“I think this study clearly demonstrates the highly effective nature of acalabrutinib in Waldenström’s macroglobulinemia,” Dr Owen stated.

 Acalabrutinib is a selective BTK inhibitor with minimal off-target activity, he said. The BTK inhibitor ibrutinib also has demonstrated activity in Waldenström’s, but has been associated with toxicities such as atrial fibrillation and bleeding, he noted.

In this phase 2 acalabrutinib study (NCT02180724), which included 14 treatment-naïve and 92 relapsed/refractory patients, atrial fibrillation occurred in 5 patients. However, 4 of those cases were grade 1-2, and only one was grade 3, according to Dr Owen.

Investigators observed grade 3 hypertension in 3 relapsed/refractory patients.

Bleeding events occurred in more than half of patients, though only 3 of those events were grade 3, and no patient discontinued treatment due to a bleeding episode.

These efficacy results are “impressive,” and the fact that very few cardiac events were seen is important, said Bruce D. Cheson, MD, of Georgetown University Medical Center in Washington, DC.

Dr Cheson commented on the acalabrutinib results in his presentation during ASCO on non-chemotherapy treatments for lymphoid malignancies.

 “One can construct a non-chemo algorithm now for Waldenström’s, for patients who are MYD88 mutated, which is more than 90% of patients,” he said. “Right now ibrutinib, and perhaps in the future acalabrutinib, can be the initial therapy with or without rituximab based on the results of ongoing trials.”

However, single non-chemotherapy agents will not be sufficient to achieve cure of lymphoid malignancies, Dr Cheson added.

“We need to carefully develop rational combinations, identifying biomarkers for response, for resistance, for toxicity,” he said.

The study was sponsored by Acerta Pharma BV. 

*Data presented at the meeting differ from the abstract.

©ASCO/Rodney White 2018

CHICAGO—Acalabrutinib monotherapy was highly effective in Waldenström’s macroglobulinemia (WM) in a phase 2 study, investigator Roger Owen, MD, reported at the 2018 ASCO Annual Meeting.

The BTK inhibitor was effective in both treatment-naïve and relapsed/refractory patients, with overall response rates for both groups in excess of 90%, and “amazing” major response rates—partial response or better—of approximately 80%, Dr Owen said.

Dr Owen, of the St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust in Leeds, UK, reported the findings as abstract 7501.*

Durations of response were excellent, according to Dr Owen, who also reported 2-year progression-free survival of 90% in treatment-naïve patients and 82% in relapsed/refractory patients.

The safety profile was favorable, with most adverse events of low grade, and a very limited number of dropouts due to adverse events, according to the investigator.

“I think this study clearly demonstrates the highly effective nature of acalabrutinib in Waldenström’s macroglobulinemia,” Dr Owen stated.

 Acalabrutinib is a selective BTK inhibitor with minimal off-target activity, he said. The BTK inhibitor ibrutinib also has demonstrated activity in Waldenström’s, but has been associated with toxicities such as atrial fibrillation and bleeding, he noted.

In this phase 2 acalabrutinib study (NCT02180724), which included 14 treatment-naïve and 92 relapsed/refractory patients, atrial fibrillation occurred in 5 patients. However, 4 of those cases were grade 1-2, and only one was grade 3, according to Dr Owen.

Investigators observed grade 3 hypertension in 3 relapsed/refractory patients.

Bleeding events occurred in more than half of patients, though only 3 of those events were grade 3, and no patient discontinued treatment due to a bleeding episode.

These efficacy results are “impressive,” and the fact that very few cardiac events were seen is important, said Bruce D. Cheson, MD, of Georgetown University Medical Center in Washington, DC.

Dr Cheson commented on the acalabrutinib results in his presentation during ASCO on non-chemotherapy treatments for lymphoid malignancies.

 “One can construct a non-chemo algorithm now for Waldenström’s, for patients who are MYD88 mutated, which is more than 90% of patients,” he said. “Right now ibrutinib, and perhaps in the future acalabrutinib, can be the initial therapy with or without rituximab based on the results of ongoing trials.”

However, single non-chemotherapy agents will not be sufficient to achieve cure of lymphoid malignancies, Dr Cheson added.

“We need to carefully develop rational combinations, identifying biomarkers for response, for resistance, for toxicity,” he said.

The study was sponsored by Acerta Pharma BV. 

*Data presented at the meeting differ from the abstract.

Adding lenalidomide to bendamustine-rituximab is not enough to offset the effects of TP53 mutations in mantle cell lymphoma (MCL), new findings suggest.

“TP53 mutated MCL remains a major challenge, and our results underline the importance of molecular profiling, including TP53 status, in future trials exploring novel agents,” wrote Christian Winther Eskelund, MD, of Rigshospitalet in Copenhagen, and his colleagues. The findings were published in Haematologica.

The researchers noted that the results will need validation in a larger cohort of patients.

They performed an analysis of 50 MCL patients who enrolled in the Nordic MCL4 trial between 2009 and 2013. Patients were either over age 65 years or were younger but unfit for autologous stem cell transplantation. Despite the addition of lenalidomide to the chemoimmunotherapy regimen, patients with TP53 mutations had worse overall and progression-free survival and were significantly quicker to experience relapse.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

[email protected]

SOURCE: Eskelund CW et al. Haematologica. 2018 May 24. doi: 10.3324/haematol.2018.194399.

Adding lenalidomide to bendamustine-rituximab is not enough to offset the effects of TP53 mutations in mantle cell lymphoma (MCL), new findings suggest.

“TP53 mutated MCL remains a major challenge, and our results underline the importance of molecular profiling, including TP53 status, in future trials exploring novel agents,” wrote Christian Winther Eskelund, MD, of Rigshospitalet in Copenhagen, and his colleagues. The findings were published in Haematologica.

The researchers noted that the results will need validation in a larger cohort of patients.

They performed an analysis of 50 MCL patients who enrolled in the Nordic MCL4 trial between 2009 and 2013. Patients were either over age 65 years or were younger but unfit for autologous stem cell transplantation. Despite the addition of lenalidomide to the chemoimmunotherapy regimen, patients with TP53 mutations had worse overall and progression-free survival and were significantly quicker to experience relapse.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

[email protected]

SOURCE: Eskelund CW et al. Haematologica. 2018 May 24. doi: 10.3324/haematol.2018.194399.

Adding lenalidomide to bendamustine-rituximab is not enough to offset the effects of TP53 mutations in mantle cell lymphoma (MCL), new findings suggest.

“TP53 mutated MCL remains a major challenge, and our results underline the importance of molecular profiling, including TP53 status, in future trials exploring novel agents,” wrote Christian Winther Eskelund, MD, of Rigshospitalet in Copenhagen, and his colleagues. The findings were published in Haematologica.

The researchers noted that the results will need validation in a larger cohort of patients.

They performed an analysis of 50 MCL patients who enrolled in the Nordic MCL4 trial between 2009 and 2013. Patients were either over age 65 years or were younger but unfit for autologous stem cell transplantation. Despite the addition of lenalidomide to the chemoimmunotherapy regimen, patients with TP53 mutations had worse overall and progression-free survival and were significantly quicker to experience relapse.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

[email protected]

SOURCE: Eskelund CW et al. Haematologica. 2018 May 24. doi: 10.3324/haematol.2018.194399.

Photo courtesy of Janssen

The 140 mg capsules of Imbruvica® (ibrutinib) will remain on the market, according to Pharmacyclics LLC.

Pharmacyclics (an AbbVie company) and Janssen had planned to discontinue the capsules after introducing a single-tablet formulation of Imbruvica earlier this year.

However, the companies received negative feedback about the discontinuation and decided to keep the 140 mg capsules on the market.

In February, the US Food and Drug Administration (FDA) approved a single-tablet formulation of Imbruvica that is available in 4 doses—140 mg, 280 mg, 420 mg, and 560 mg.

Pharmacyclics and Janssen introduced this formulation to enable a once-a-day dosing regimen. The companies said the goal with the new formulation was to improve adherence because some patients had to take 3 or 4 pills every day to get the recommended dose of Imbruvica.

After introducing the new formulation, Pharmacyclics and Janssen planned to discontinue the 140 mg capsules.

Critics spoke out against this change in an article published in The Cancer Letter. They noted that discontinuing the old formulation would mean price increases for some patients. That’s because the single-tablet formulation of Imbruvica has the same price regardless of dose—$400 per tablet.

Patients on lower doses of Imbruvica would experience an increase in cost if they switched from the capsules to the tablet formulation. In fact, costs could triple for patients on the 140 mg dose.

Pharmacyclics argued that most patients on Imbruvica—those taking the 420 mg and 560 mg doses—would see no increase in out-of-pocket costs when transitioning to the single-tablet formulation.  And patients on the 560 mg dose would likely see a decrease in their out-of-pocket costs.

However, critics pointed to results of a recent pilot study, which indicated that the recommended dose of Imbruvica for patients with chronic lymphocytic leukemia (CLL)—420 mg—may be too high. The results suggested that CLL patients could receive lower doses of Imbruvica without a reduction in efficacy.

Therefore, keeping the 140 mg capsules on the market could mean lower costs for some CLL patients.

In addition to voicing concerns about costs, the critics pointed out that discontinuing the 140 mg capsules of Imbruvica would make it more difficult to adjust patients’ doses when needed.

Pharmacyclics said its YOU&i™ Dose Exchange Program can aid healthcare professionals in adjusting doses before patients have finished their current pack of Imbruvica. Patients would receive a “rapid shipment” of their new dose at no additional cost.

But the critics said this program “creates a barrier to optimal prescribing for some patients” and urged the FDA to review the safety of the program.

Roughly a month after the critics made this recommendation in The Cancer Letter article, Pharmacyclics announced that the 140 mg capsules of Imbruvica would remain on the market.

Photo courtesy of Janssen

The 140 mg capsules of Imbruvica® (ibrutinib) will remain on the market, according to Pharmacyclics LLC.

Pharmacyclics (an AbbVie company) and Janssen had planned to discontinue the capsules after introducing a single-tablet formulation of Imbruvica earlier this year.

However, the companies received negative feedback about the discontinuation and decided to keep the 140 mg capsules on the market.

In February, the US Food and Drug Administration (FDA) approved a single-tablet formulation of Imbruvica that is available in 4 doses—140 mg, 280 mg, 420 mg, and 560 mg.

Pharmacyclics and Janssen introduced this formulation to enable a once-a-day dosing regimen. The companies said the goal with the new formulation was to improve adherence because some patients had to take 3 or 4 pills every day to get the recommended dose of Imbruvica.

After introducing the new formulation, Pharmacyclics and Janssen planned to discontinue the 140 mg capsules.

Critics spoke out against this change in an article published in The Cancer Letter. They noted that discontinuing the old formulation would mean price increases for some patients. That’s because the single-tablet formulation of Imbruvica has the same price regardless of dose—$400 per tablet.

Patients on lower doses of Imbruvica would experience an increase in cost if they switched from the capsules to the tablet formulation. In fact, costs could triple for patients on the 140 mg dose.

Pharmacyclics argued that most patients on Imbruvica—those taking the 420 mg and 560 mg doses—would see no increase in out-of-pocket costs when transitioning to the single-tablet formulation.  And patients on the 560 mg dose would likely see a decrease in their out-of-pocket costs.

However, critics pointed to results of a recent pilot study, which indicated that the recommended dose of Imbruvica for patients with chronic lymphocytic leukemia (CLL)—420 mg—may be too high. The results suggested that CLL patients could receive lower doses of Imbruvica without a reduction in efficacy.

Therefore, keeping the 140 mg capsules on the market could mean lower costs for some CLL patients.

In addition to voicing concerns about costs, the critics pointed out that discontinuing the 140 mg capsules of Imbruvica would make it more difficult to adjust patients’ doses when needed.

Pharmacyclics said its YOU&i™ Dose Exchange Program can aid healthcare professionals in adjusting doses before patients have finished their current pack of Imbruvica. Patients would receive a “rapid shipment” of their new dose at no additional cost.

But the critics said this program “creates a barrier to optimal prescribing for some patients” and urged the FDA to review the safety of the program.

Roughly a month after the critics made this recommendation in The Cancer Letter article, Pharmacyclics announced that the 140 mg capsules of Imbruvica would remain on the market.

Photo courtesy of Janssen

The 140 mg capsules of Imbruvica® (ibrutinib) will remain on the market, according to Pharmacyclics LLC.

Pharmacyclics (an AbbVie company) and Janssen had planned to discontinue the capsules after introducing a single-tablet formulation of Imbruvica earlier this year.

However, the companies received negative feedback about the discontinuation and decided to keep the 140 mg capsules on the market.

In February, the US Food and Drug Administration (FDA) approved a single-tablet formulation of Imbruvica that is available in 4 doses—140 mg, 280 mg, 420 mg, and 560 mg.

Pharmacyclics and Janssen introduced this formulation to enable a once-a-day dosing regimen. The companies said the goal with the new formulation was to improve adherence because some patients had to take 3 or 4 pills every day to get the recommended dose of Imbruvica.

After introducing the new formulation, Pharmacyclics and Janssen planned to discontinue the 140 mg capsules.

Critics spoke out against this change in an article published in The Cancer Letter. They noted that discontinuing the old formulation would mean price increases for some patients. That’s because the single-tablet formulation of Imbruvica has the same price regardless of dose—$400 per tablet.

Patients on lower doses of Imbruvica would experience an increase in cost if they switched from the capsules to the tablet formulation. In fact, costs could triple for patients on the 140 mg dose.

Pharmacyclics argued that most patients on Imbruvica—those taking the 420 mg and 560 mg doses—would see no increase in out-of-pocket costs when transitioning to the single-tablet formulation.  And patients on the 560 mg dose would likely see a decrease in their out-of-pocket costs.

However, critics pointed to results of a recent pilot study, which indicated that the recommended dose of Imbruvica for patients with chronic lymphocytic leukemia (CLL)—420 mg—may be too high. The results suggested that CLL patients could receive lower doses of Imbruvica without a reduction in efficacy.

Therefore, keeping the 140 mg capsules on the market could mean lower costs for some CLL patients.

In addition to voicing concerns about costs, the critics pointed out that discontinuing the 140 mg capsules of Imbruvica would make it more difficult to adjust patients’ doses when needed.

Pharmacyclics said its YOU&i™ Dose Exchange Program can aid healthcare professionals in adjusting doses before patients have finished their current pack of Imbruvica. Patients would receive a “rapid shipment” of their new dose at no additional cost.

But the critics said this program “creates a barrier to optimal prescribing for some patients” and urged the FDA to review the safety of the program.

Roughly a month after the critics made this recommendation in The Cancer Letter article, Pharmacyclics announced that the 140 mg capsules of Imbruvica would remain on the market.

PITTSBURGH – The incidence of many pediatric cancers are on the rise, and the increase is occurring in nearly all demographic groups studied, according to the latest data from the U.S. Centers for Disease Control and Prevention.

Pediatric cancers that increased significantly in incidence from 2001 through 2014, compared with previous time periods, include thyroid carcinoma, hepatic tumors, lymphomas, renal tumors, and brain tumors. Other cancer types remained unchanged, except malignant melanoma, which saw a significant decline in incidence over the same period, reported David A. Siegel, MD, of the Epidemic Intelligence Service at the CDC in Atlanta.

Neil Osterweil/MDedge News

SOURCE: Siegel DA et al. ASPHO 2018, Abstract 605.

PITTSBURGH – The incidence of many pediatric cancers are on the rise, and the increase is occurring in nearly all demographic groups studied, according to the latest data from the U.S. Centers for Disease Control and Prevention.

Pediatric cancers that increased significantly in incidence from 2001 through 2014, compared with previous time periods, include thyroid carcinoma, hepatic tumors, lymphomas, renal tumors, and brain tumors. Other cancer types remained unchanged, except malignant melanoma, which saw a significant decline in incidence over the same period, reported David A. Siegel, MD, of the Epidemic Intelligence Service at the CDC in Atlanta.

Neil Osterweil/MDedge News

SOURCE: Siegel DA et al. ASPHO 2018, Abstract 605.

PITTSBURGH – The incidence of many pediatric cancers are on the rise, and the increase is occurring in nearly all demographic groups studied, according to the latest data from the U.S. Centers for Disease Control and Prevention.

Pediatric cancers that increased significantly in incidence from 2001 through 2014, compared with previous time periods, include thyroid carcinoma, hepatic tumors, lymphomas, renal tumors, and brain tumors. Other cancer types remained unchanged, except malignant melanoma, which saw a significant decline in incidence over the same period, reported David A. Siegel, MD, of the Epidemic Intelligence Service at the CDC in Atlanta.

Neil Osterweil/MDedge News

SOURCE: Siegel DA et al. ASPHO 2018, Abstract 605.