Aggressive Lymphomas

Poster session at the 23rd Congress of the European Hematology Association

STOCKHOLM—The dual SYK/JAK inhibitor cerdulatinib has demonstrated efficacy in a phase 2 trial of patients with heavily pretreated B- and T-cell non-Hodgkin lymphomas (NHLs).

There were a few deaths due to sepsis or septic shock that were considered related to cerdulatinib, but investigators have taken steps to prevent additional deaths.

Cerdulatinib produced responses in patients with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), follicular lymphoma (FL), and other NHLs.

The 5 deaths due to sepsis or septic shock (3 concomitant with pneumonia) occurred early on in the trial, and dose reductions, monitoring, and antibiotic prophylaxis appeared to be effective in preventing additional deaths.

Results from this trial were presented in a poster (abstract PF437) at the 23rd Congress of the European Hematology Association (EHA).

The research was sponsored by Portola Pharmaceuticals, Inc.

The trial enrolled 114 patients. They had FL (grade 1-3A; n=39), PTCL (n=25), CTCL (n=5), CLL/SLL (n=28), other indolent NHLs (Waldenstrom’s macroglobulinemia and marginal zone lymphoma; n=12), or aggressive NHL (defined as diffuse large B-cell lymphoma [DLBCL], grade 3B FL, mantle cell lymphoma, and transformed NHL with relapsed disease; n=5).

The patients’ median age was 68 (range, 34-93), and 59% were male. The median number of prior treatment regimens was 3 (range, 1-13), and 37% of patients had refractory disease.

Patients received cerdulatinib at 25, 30, or 35 mg twice daily (BID). A total of 101 patients were evaluable as of May 4, 2018.

Response

The objective response rate (ORR) was 47% in the entire population. Thirteen patients achieved a complete response (CR), and 34 had a partial response (PR). Thirty-four patients remained on cerdulatinib at the data cut-off.

The ORR was 46% in the FL patients, with 3 patients achieving a CR and 13 achieving a PR. Thirteen FL patients remained on cerdulatinib.

In the CLL/SLL patients, the ORR was 61%. Two patients had a CR, and 15 had a PR. Four CLL/SLL patients remained on cerdulatinib.

In PTCL, the ORR was 35%. All 7 responders had a CR. Eleven PTCL patients remained on cerdulatinib.

Only 1 CTCL patient was evaluable, but this patient achieved a CR and remained on cerdulatinib.

The ORR was 42% for patients with other indolent NHLs, with 5 PRs and no CRs. Only 1 patient in this group remained on cerdulatinib.

For aggressive NHL, the ORR was 20%, with 1 PR and no CRs. None of the patients in this group stayed on cerdulatinib.

“Cerdulatinib continues to demonstrate promising results across a wide range of B- and T-cell malignancies, including early indications of the potential for durable responses,” said study investigator Paul Hamlin, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.

“The new signals in relapsed/refractory PTCL and CTCL are particularly compelling when you consider the limited treatment options for patients that fail frontline therapy.”

Safety

Grade 3 or higher adverse events included lipase increase (18%), neutropenia (17%), pneumonia/lung infection (11%), diarrhea (8%), fatigue (6%), amylase increase (5%), sepsis/septic shock (4%), hypertension (4%), anemia (4%), thrombocytopenia (4%), and hypophosphatemia (4%).

The 5 deaths due to sepsis or septic shock (3 of which were concomitant with pneumonia) were considered related to cerdulatinib. Three of the deaths occurred in patients with CLL, 1 in a DLBCL patient, and 1 in an FL patient.

“One of the things we have seen [with CLL patients] is the background infection rate is quite a bit higher,” said John T. Curnutte, MD, PhD, interim co-president and head of research and development at Portola Pharmaceuticals.

“You see this with multiple other agents, so we were not particularly surprised to see [sepsis/septic shock in CLL].”

Dr Curnutte noted that grade 5 sepsis/septic shock tended to occur in patients who were pre-colonized and/or had high plasma levels of cerdulatinib.

So, to prevent these adverse events, the starting dose of cerdulatinib was lowered, investigators began monitoring patients’ plasma levels, and all patients began receiving antibiotic prophylaxis. (Previously, only CLL patients had received this prophylaxis.)

The investigators found that lowering the starting dose from 35 mg BID to 30 mg or even 25 mg BID reduced plasma levels.

“At the 35 mg dose, 1 out of every 4 patients showed accumulation of the drug,” Dr Curnutte said. “In general, the use of the 30 mg BID or step-down 25 mg BID did not result in accumulation of drug.”

Dr Curnutte also noted that enrollment of CLL/SLL patients is complete, and investigators would be “very careful” if the study were to be re-opened to these patients.

For now, Portola is focused on completing enrollment in other patient groups on this phase 2 trial. The company is also hoping to conduct a phase 3 trial of cerdulatinib in PTCL that could begin as early as the end of this year.

Poster session at the 23rd Congress of the European Hematology Association

STOCKHOLM—The dual SYK/JAK inhibitor cerdulatinib has demonstrated efficacy in a phase 2 trial of patients with heavily pretreated B- and T-cell non-Hodgkin lymphomas (NHLs).

There were a few deaths due to sepsis or septic shock that were considered related to cerdulatinib, but investigators have taken steps to prevent additional deaths.

Cerdulatinib produced responses in patients with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), follicular lymphoma (FL), and other NHLs.

The 5 deaths due to sepsis or septic shock (3 concomitant with pneumonia) occurred early on in the trial, and dose reductions, monitoring, and antibiotic prophylaxis appeared to be effective in preventing additional deaths.

Results from this trial were presented in a poster (abstract PF437) at the 23rd Congress of the European Hematology Association (EHA).

The research was sponsored by Portola Pharmaceuticals, Inc.

The trial enrolled 114 patients. They had FL (grade 1-3A; n=39), PTCL (n=25), CTCL (n=5), CLL/SLL (n=28), other indolent NHLs (Waldenstrom’s macroglobulinemia and marginal zone lymphoma; n=12), or aggressive NHL (defined as diffuse large B-cell lymphoma [DLBCL], grade 3B FL, mantle cell lymphoma, and transformed NHL with relapsed disease; n=5).

The patients’ median age was 68 (range, 34-93), and 59% were male. The median number of prior treatment regimens was 3 (range, 1-13), and 37% of patients had refractory disease.

Patients received cerdulatinib at 25, 30, or 35 mg twice daily (BID). A total of 101 patients were evaluable as of May 4, 2018.

Response

The objective response rate (ORR) was 47% in the entire population. Thirteen patients achieved a complete response (CR), and 34 had a partial response (PR). Thirty-four patients remained on cerdulatinib at the data cut-off.

The ORR was 46% in the FL patients, with 3 patients achieving a CR and 13 achieving a PR. Thirteen FL patients remained on cerdulatinib.

In the CLL/SLL patients, the ORR was 61%. Two patients had a CR, and 15 had a PR. Four CLL/SLL patients remained on cerdulatinib.

In PTCL, the ORR was 35%. All 7 responders had a CR. Eleven PTCL patients remained on cerdulatinib.

Only 1 CTCL patient was evaluable, but this patient achieved a CR and remained on cerdulatinib.

The ORR was 42% for patients with other indolent NHLs, with 5 PRs and no CRs. Only 1 patient in this group remained on cerdulatinib.

For aggressive NHL, the ORR was 20%, with 1 PR and no CRs. None of the patients in this group stayed on cerdulatinib.

“Cerdulatinib continues to demonstrate promising results across a wide range of B- and T-cell malignancies, including early indications of the potential for durable responses,” said study investigator Paul Hamlin, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.

“The new signals in relapsed/refractory PTCL and CTCL are particularly compelling when you consider the limited treatment options for patients that fail frontline therapy.”

Safety

Grade 3 or higher adverse events included lipase increase (18%), neutropenia (17%), pneumonia/lung infection (11%), diarrhea (8%), fatigue (6%), amylase increase (5%), sepsis/septic shock (4%), hypertension (4%), anemia (4%), thrombocytopenia (4%), and hypophosphatemia (4%).

The 5 deaths due to sepsis or septic shock (3 of which were concomitant with pneumonia) were considered related to cerdulatinib. Three of the deaths occurred in patients with CLL, 1 in a DLBCL patient, and 1 in an FL patient.

“One of the things we have seen [with CLL patients] is the background infection rate is quite a bit higher,” said John T. Curnutte, MD, PhD, interim co-president and head of research and development at Portola Pharmaceuticals.

“You see this with multiple other agents, so we were not particularly surprised to see [sepsis/septic shock in CLL].”

Dr Curnutte noted that grade 5 sepsis/septic shock tended to occur in patients who were pre-colonized and/or had high plasma levels of cerdulatinib.

So, to prevent these adverse events, the starting dose of cerdulatinib was lowered, investigators began monitoring patients’ plasma levels, and all patients began receiving antibiotic prophylaxis. (Previously, only CLL patients had received this prophylaxis.)

The investigators found that lowering the starting dose from 35 mg BID to 30 mg or even 25 mg BID reduced plasma levels.

“At the 35 mg dose, 1 out of every 4 patients showed accumulation of the drug,” Dr Curnutte said. “In general, the use of the 30 mg BID or step-down 25 mg BID did not result in accumulation of drug.”

Dr Curnutte also noted that enrollment of CLL/SLL patients is complete, and investigators would be “very careful” if the study were to be re-opened to these patients.

For now, Portola is focused on completing enrollment in other patient groups on this phase 2 trial. The company is also hoping to conduct a phase 3 trial of cerdulatinib in PTCL that could begin as early as the end of this year.

Poster session at the 23rd Congress of the European Hematology Association

STOCKHOLM—The dual SYK/JAK inhibitor cerdulatinib has demonstrated efficacy in a phase 2 trial of patients with heavily pretreated B- and T-cell non-Hodgkin lymphomas (NHLs).

There were a few deaths due to sepsis or septic shock that were considered related to cerdulatinib, but investigators have taken steps to prevent additional deaths.

Cerdulatinib produced responses in patients with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), follicular lymphoma (FL), and other NHLs.

The 5 deaths due to sepsis or septic shock (3 concomitant with pneumonia) occurred early on in the trial, and dose reductions, monitoring, and antibiotic prophylaxis appeared to be effective in preventing additional deaths.

Results from this trial were presented in a poster (abstract PF437) at the 23rd Congress of the European Hematology Association (EHA).

The research was sponsored by Portola Pharmaceuticals, Inc.

The trial enrolled 114 patients. They had FL (grade 1-3A; n=39), PTCL (n=25), CTCL (n=5), CLL/SLL (n=28), other indolent NHLs (Waldenstrom’s macroglobulinemia and marginal zone lymphoma; n=12), or aggressive NHL (defined as diffuse large B-cell lymphoma [DLBCL], grade 3B FL, mantle cell lymphoma, and transformed NHL with relapsed disease; n=5).

The patients’ median age was 68 (range, 34-93), and 59% were male. The median number of prior treatment regimens was 3 (range, 1-13), and 37% of patients had refractory disease.

Patients received cerdulatinib at 25, 30, or 35 mg twice daily (BID). A total of 101 patients were evaluable as of May 4, 2018.

Response

The objective response rate (ORR) was 47% in the entire population. Thirteen patients achieved a complete response (CR), and 34 had a partial response (PR). Thirty-four patients remained on cerdulatinib at the data cut-off.

The ORR was 46% in the FL patients, with 3 patients achieving a CR and 13 achieving a PR. Thirteen FL patients remained on cerdulatinib.

In the CLL/SLL patients, the ORR was 61%. Two patients had a CR, and 15 had a PR. Four CLL/SLL patients remained on cerdulatinib.

In PTCL, the ORR was 35%. All 7 responders had a CR. Eleven PTCL patients remained on cerdulatinib.

Only 1 CTCL patient was evaluable, but this patient achieved a CR and remained on cerdulatinib.

The ORR was 42% for patients with other indolent NHLs, with 5 PRs and no CRs. Only 1 patient in this group remained on cerdulatinib.

For aggressive NHL, the ORR was 20%, with 1 PR and no CRs. None of the patients in this group stayed on cerdulatinib.

“Cerdulatinib continues to demonstrate promising results across a wide range of B- and T-cell malignancies, including early indications of the potential for durable responses,” said study investigator Paul Hamlin, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.

“The new signals in relapsed/refractory PTCL and CTCL are particularly compelling when you consider the limited treatment options for patients that fail frontline therapy.”

Safety

Grade 3 or higher adverse events included lipase increase (18%), neutropenia (17%), pneumonia/lung infection (11%), diarrhea (8%), fatigue (6%), amylase increase (5%), sepsis/septic shock (4%), hypertension (4%), anemia (4%), thrombocytopenia (4%), and hypophosphatemia (4%).

The 5 deaths due to sepsis or septic shock (3 of which were concomitant with pneumonia) were considered related to cerdulatinib. Three of the deaths occurred in patients with CLL, 1 in a DLBCL patient, and 1 in an FL patient.

“One of the things we have seen [with CLL patients] is the background infection rate is quite a bit higher,” said John T. Curnutte, MD, PhD, interim co-president and head of research and development at Portola Pharmaceuticals.

“You see this with multiple other agents, so we were not particularly surprised to see [sepsis/septic shock in CLL].”

Dr Curnutte noted that grade 5 sepsis/septic shock tended to occur in patients who were pre-colonized and/or had high plasma levels of cerdulatinib.

So, to prevent these adverse events, the starting dose of cerdulatinib was lowered, investigators began monitoring patients’ plasma levels, and all patients began receiving antibiotic prophylaxis. (Previously, only CLL patients had received this prophylaxis.)

The investigators found that lowering the starting dose from 35 mg BID to 30 mg or even 25 mg BID reduced plasma levels.

“At the 35 mg dose, 1 out of every 4 patients showed accumulation of the drug,” Dr Curnutte said. “In general, the use of the 30 mg BID or step-down 25 mg BID did not result in accumulation of drug.”

Dr Curnutte also noted that enrollment of CLL/SLL patients is complete, and investigators would be “very careful” if the study were to be re-opened to these patients.

For now, Portola is focused on completing enrollment in other patient groups on this phase 2 trial. The company is also hoping to conduct a phase 3 trial of cerdulatinib in PTCL that could begin as early as the end of this year.

Valentin Goede, MD

STOCKHOLM—Obinutuzumab plus chlorambucil (G-Clb) is a “valid and beneficial” frontline treatment option for “unfit” patients with chronic lymphocytic leukemia (CLL), according to a speaker at the 23rd Congress of the European Hematology Association (EHA).

Final results from the CLL11 study have revealed additional benefits of G-Clb over rituximab plus chlorambucil (R-Clb) in patients with previously untreated CLL and comorbidities.

Prior results from this study showed that G-Clb produced higher response rates and prolonged progression-fee survival (PFS) compared to R-Clb.

Now, with a median follow-up of 5 years, researchers have found that G-Clb prolongs overall survival (OS) and time to next treatment (TTNT) as well.

Valentin Goede, MD, of the University Hospital Cologne in Germany, presented these results during the Presidential Symposium of the EHA Congress (abstract S151).

The study was sponsored by Hoffmann-La Roche.

CLL11 enrolled patients with previously untreated CLL and coexisting medical conditions. They were randomized to receive six 28-day cycles of Clb alone, G-Clb, or R-Clb.

In stage 1, researchers compared G-Clb (n=238) to Clb alone (n=118) and R-Clb (n=233) to Clb alone (n=118). In stage 2, they compared G-Clb (n=333) and R-Clb (n=330).

“The treatment arms were well-balanced, not just with regard to patient [characteristics] but also with disease characteristics,” Dr Goede said.

Overall, the median age was 73 (range, 39-90), the median Cumulative Illness Rating Scale score was 8, and the median creatinine clearance was 62 mL/min.

Efficacy: G-Clb vs Clb

The median observation time for G-Clb vs Clb was 62.5 months.

The median PFS was 31.1 months in the G-Clb arm and 11.1 months in the Clb arm. The 5-year PFS rates were 25% and 2%, respectively. The hazard ratio (HR) was 0.21 (P<0.0001).

The median OS was not reached in the G-Clb arm and was 66.7 months in the Clb arm. The 5-year OS rates were 66% and 53%, respectively. The HR was 0.68 (P=0.0196).

Thirty-nine percent of the G-Clb arm died, as did 49% of the Clb arm. The main causes of death were adverse events (AEs) and disease progression.

Efficacy: G-Clb vs R-Clb

The median observation time for G-Clb vs R-Clb was 59.4 months.

The median PFS was 28.9 months in the G-Clb arm and 15.7 months in the R-Clb arm. The 5-year PFS rates were 23% and 9%, respectively. The HR was 0.49 (P<0.0001).

“The median PFS was nearly doubled, from approximately 15 months in the rituximab arm to almost 30 months in the obinutuzumab arm,” Dr Goede said. “And this translated into a clinically meaningful prolongation of time to next treatment.”

The median TTNT was 56.4 months in the G-Clb arm and 34.9 months in the R-Clb arm. At 5 years, TTNT rates were 49% and 32%, respectively. The HR was 0.58 (P<0.0001).

“In the rituximab arm, the median time to next treatment was a little greater than 2.5 years, and, in the obinutuzumab arm, it was almost 5 years,” Dr Goede said. “From a clinical perspective, I would consider treatment-free intervals of that duration as highly relevant and beneficial in an elderly population.”

The median OS was not reached in the G-Clb arm and was 73.1 months in the R-Clb arm. The 5-year OS rates were 66% and 57%, respectively. The HR was 0.76 (P=0.0245).

“This difference is clinically meaningful, and it is also remarkable in the context of the long follow-up, given the fact that approximately half of the patients have received at least 1 salvage treatment in the meantime,” Dr Goede said.

In all, 37% of the G-Clb arm died, as did 45% of the R-Clb arm. Again, the main causes of death were AEs and disease progression.

Safety

Dr Goede said no new safety signals or late-onset toxicities were detected.

“Adverse events of any grade, but particularly grade 3-5 and serious adverse events, were more frequent in the obinutuzumab arm compared to the other 2 arms,” he noted. “[This] was mainly driven by more infusion reactions and some greater hematological toxicity.”

“Importantly, the rate of fatal adverse events, during treatment but also during follow-up, was not higher in the obinutuzumab arm. And the most common fatal adverse events were second malignancies.”

G-Clb vs Clb

Ninety-five percent of patients in the G-Clb arm and 83% of those in the Clb arm had at least 1 AE. The rates of grade 3-5 AEs were 74% and 51%, respectively. The rates of serious AEs were 47% and 39%, respectively. The rates of fatal AEs were 8% and 11%, respectively.

Seventeen percent of patients in the G-Clb arm and 11% of those in the Clb arm had late-onset neutropenia. The rates of prolonged neutropenia were 3% and 9%, respectively.

Fourteen percent of patients in the G-Clb arm and 7% of those in the Clb arm had second malignancies (starting 6 months after treatment initiation). The most common of these were squamous cell carcinoma (2% vs 0%) and basal cell carcinoma (2% vs <1%).

G-Clb vs R-Clb

Ninety-four percent of patients in the G-Clb arm and 90% of those in the R-Clb arm had at least 1 AE. The rates of grade 3-5 AEs were 72% and 60%, respectively. The rates of serious AEs were 45% and 39%, respectively. The rates of fatal AEs were 7% and 10%, respectively.

Fifteen percent of patients in the G-Clb arm and 12% of those in the R-Clb arm had late-onset neutropenia. The rates of prolonged neutropenia were 2% and 4%, respectively.

Eleven percent of patients in the G-Clb arm and 10% of those in the Clb arm had second malignancies. Squamous cell carcinoma occurred in 2% of patients in both arms. Basal cell carcinoma occurred in 2% of G-Clb recipients and 1% of R-Clb recipients.

Valentin Goede, MD

STOCKHOLM—Obinutuzumab plus chlorambucil (G-Clb) is a “valid and beneficial” frontline treatment option for “unfit” patients with chronic lymphocytic leukemia (CLL), according to a speaker at the 23rd Congress of the European Hematology Association (EHA).

Final results from the CLL11 study have revealed additional benefits of G-Clb over rituximab plus chlorambucil (R-Clb) in patients with previously untreated CLL and comorbidities.

Prior results from this study showed that G-Clb produced higher response rates and prolonged progression-fee survival (PFS) compared to R-Clb.

Now, with a median follow-up of 5 years, researchers have found that G-Clb prolongs overall survival (OS) and time to next treatment (TTNT) as well.

Valentin Goede, MD, of the University Hospital Cologne in Germany, presented these results during the Presidential Symposium of the EHA Congress (abstract S151).

The study was sponsored by Hoffmann-La Roche.

CLL11 enrolled patients with previously untreated CLL and coexisting medical conditions. They were randomized to receive six 28-day cycles of Clb alone, G-Clb, or R-Clb.

In stage 1, researchers compared G-Clb (n=238) to Clb alone (n=118) and R-Clb (n=233) to Clb alone (n=118). In stage 2, they compared G-Clb (n=333) and R-Clb (n=330).

“The treatment arms were well-balanced, not just with regard to patient [characteristics] but also with disease characteristics,” Dr Goede said.

Overall, the median age was 73 (range, 39-90), the median Cumulative Illness Rating Scale score was 8, and the median creatinine clearance was 62 mL/min.

Efficacy: G-Clb vs Clb

The median observation time for G-Clb vs Clb was 62.5 months.

The median PFS was 31.1 months in the G-Clb arm and 11.1 months in the Clb arm. The 5-year PFS rates were 25% and 2%, respectively. The hazard ratio (HR) was 0.21 (P<0.0001).

The median OS was not reached in the G-Clb arm and was 66.7 months in the Clb arm. The 5-year OS rates were 66% and 53%, respectively. The HR was 0.68 (P=0.0196).

Thirty-nine percent of the G-Clb arm died, as did 49% of the Clb arm. The main causes of death were adverse events (AEs) and disease progression.

Efficacy: G-Clb vs R-Clb

The median observation time for G-Clb vs R-Clb was 59.4 months.

The median PFS was 28.9 months in the G-Clb arm and 15.7 months in the R-Clb arm. The 5-year PFS rates were 23% and 9%, respectively. The HR was 0.49 (P<0.0001).

“The median PFS was nearly doubled, from approximately 15 months in the rituximab arm to almost 30 months in the obinutuzumab arm,” Dr Goede said. “And this translated into a clinically meaningful prolongation of time to next treatment.”

The median TTNT was 56.4 months in the G-Clb arm and 34.9 months in the R-Clb arm. At 5 years, TTNT rates were 49% and 32%, respectively. The HR was 0.58 (P<0.0001).

“In the rituximab arm, the median time to next treatment was a little greater than 2.5 years, and, in the obinutuzumab arm, it was almost 5 years,” Dr Goede said. “From a clinical perspective, I would consider treatment-free intervals of that duration as highly relevant and beneficial in an elderly population.”

The median OS was not reached in the G-Clb arm and was 73.1 months in the R-Clb arm. The 5-year OS rates were 66% and 57%, respectively. The HR was 0.76 (P=0.0245).

“This difference is clinically meaningful, and it is also remarkable in the context of the long follow-up, given the fact that approximately half of the patients have received at least 1 salvage treatment in the meantime,” Dr Goede said.

In all, 37% of the G-Clb arm died, as did 45% of the R-Clb arm. Again, the main causes of death were AEs and disease progression.

Safety

Dr Goede said no new safety signals or late-onset toxicities were detected.

“Adverse events of any grade, but particularly grade 3-5 and serious adverse events, were more frequent in the obinutuzumab arm compared to the other 2 arms,” he noted. “[This] was mainly driven by more infusion reactions and some greater hematological toxicity.”

“Importantly, the rate of fatal adverse events, during treatment but also during follow-up, was not higher in the obinutuzumab arm. And the most common fatal adverse events were second malignancies.”

G-Clb vs Clb

Ninety-five percent of patients in the G-Clb arm and 83% of those in the Clb arm had at least 1 AE. The rates of grade 3-5 AEs were 74% and 51%, respectively. The rates of serious AEs were 47% and 39%, respectively. The rates of fatal AEs were 8% and 11%, respectively.

Seventeen percent of patients in the G-Clb arm and 11% of those in the Clb arm had late-onset neutropenia. The rates of prolonged neutropenia were 3% and 9%, respectively.

Fourteen percent of patients in the G-Clb arm and 7% of those in the Clb arm had second malignancies (starting 6 months after treatment initiation). The most common of these were squamous cell carcinoma (2% vs 0%) and basal cell carcinoma (2% vs <1%).

G-Clb vs R-Clb

Ninety-four percent of patients in the G-Clb arm and 90% of those in the R-Clb arm had at least 1 AE. The rates of grade 3-5 AEs were 72% and 60%, respectively. The rates of serious AEs were 45% and 39%, respectively. The rates of fatal AEs were 7% and 10%, respectively.

Fifteen percent of patients in the G-Clb arm and 12% of those in the R-Clb arm had late-onset neutropenia. The rates of prolonged neutropenia were 2% and 4%, respectively.

Eleven percent of patients in the G-Clb arm and 10% of those in the Clb arm had second malignancies. Squamous cell carcinoma occurred in 2% of patients in both arms. Basal cell carcinoma occurred in 2% of G-Clb recipients and 1% of R-Clb recipients.

Valentin Goede, MD

STOCKHOLM—Obinutuzumab plus chlorambucil (G-Clb) is a “valid and beneficial” frontline treatment option for “unfit” patients with chronic lymphocytic leukemia (CLL), according to a speaker at the 23rd Congress of the European Hematology Association (EHA).

Final results from the CLL11 study have revealed additional benefits of G-Clb over rituximab plus chlorambucil (R-Clb) in patients with previously untreated CLL and comorbidities.

Prior results from this study showed that G-Clb produced higher response rates and prolonged progression-fee survival (PFS) compared to R-Clb.

Now, with a median follow-up of 5 years, researchers have found that G-Clb prolongs overall survival (OS) and time to next treatment (TTNT) as well.

Valentin Goede, MD, of the University Hospital Cologne in Germany, presented these results during the Presidential Symposium of the EHA Congress (abstract S151).

The study was sponsored by Hoffmann-La Roche.

CLL11 enrolled patients with previously untreated CLL and coexisting medical conditions. They were randomized to receive six 28-day cycles of Clb alone, G-Clb, or R-Clb.

In stage 1, researchers compared G-Clb (n=238) to Clb alone (n=118) and R-Clb (n=233) to Clb alone (n=118). In stage 2, they compared G-Clb (n=333) and R-Clb (n=330).

“The treatment arms were well-balanced, not just with regard to patient [characteristics] but also with disease characteristics,” Dr Goede said.

Overall, the median age was 73 (range, 39-90), the median Cumulative Illness Rating Scale score was 8, and the median creatinine clearance was 62 mL/min.

Efficacy: G-Clb vs Clb

The median observation time for G-Clb vs Clb was 62.5 months.

The median PFS was 31.1 months in the G-Clb arm and 11.1 months in the Clb arm. The 5-year PFS rates were 25% and 2%, respectively. The hazard ratio (HR) was 0.21 (P<0.0001).

The median OS was not reached in the G-Clb arm and was 66.7 months in the Clb arm. The 5-year OS rates were 66% and 53%, respectively. The HR was 0.68 (P=0.0196).

Thirty-nine percent of the G-Clb arm died, as did 49% of the Clb arm. The main causes of death were adverse events (AEs) and disease progression.

Efficacy: G-Clb vs R-Clb

The median observation time for G-Clb vs R-Clb was 59.4 months.

The median PFS was 28.9 months in the G-Clb arm and 15.7 months in the R-Clb arm. The 5-year PFS rates were 23% and 9%, respectively. The HR was 0.49 (P<0.0001).

“The median PFS was nearly doubled, from approximately 15 months in the rituximab arm to almost 30 months in the obinutuzumab arm,” Dr Goede said. “And this translated into a clinically meaningful prolongation of time to next treatment.”

The median TTNT was 56.4 months in the G-Clb arm and 34.9 months in the R-Clb arm. At 5 years, TTNT rates were 49% and 32%, respectively. The HR was 0.58 (P<0.0001).

“In the rituximab arm, the median time to next treatment was a little greater than 2.5 years, and, in the obinutuzumab arm, it was almost 5 years,” Dr Goede said. “From a clinical perspective, I would consider treatment-free intervals of that duration as highly relevant and beneficial in an elderly population.”

The median OS was not reached in the G-Clb arm and was 73.1 months in the R-Clb arm. The 5-year OS rates were 66% and 57%, respectively. The HR was 0.76 (P=0.0245).

“This difference is clinically meaningful, and it is also remarkable in the context of the long follow-up, given the fact that approximately half of the patients have received at least 1 salvage treatment in the meantime,” Dr Goede said.

In all, 37% of the G-Clb arm died, as did 45% of the R-Clb arm. Again, the main causes of death were AEs and disease progression.

Safety

Dr Goede said no new safety signals or late-onset toxicities were detected.

“Adverse events of any grade, but particularly grade 3-5 and serious adverse events, were more frequent in the obinutuzumab arm compared to the other 2 arms,” he noted. “[This] was mainly driven by more infusion reactions and some greater hematological toxicity.”

“Importantly, the rate of fatal adverse events, during treatment but also during follow-up, was not higher in the obinutuzumab arm. And the most common fatal adverse events were second malignancies.”

G-Clb vs Clb

Ninety-five percent of patients in the G-Clb arm and 83% of those in the Clb arm had at least 1 AE. The rates of grade 3-5 AEs were 74% and 51%, respectively. The rates of serious AEs were 47% and 39%, respectively. The rates of fatal AEs were 8% and 11%, respectively.

Seventeen percent of patients in the G-Clb arm and 11% of those in the Clb arm had late-onset neutropenia. The rates of prolonged neutropenia were 3% and 9%, respectively.

Fourteen percent of patients in the G-Clb arm and 7% of those in the Clb arm had second malignancies (starting 6 months after treatment initiation). The most common of these were squamous cell carcinoma (2% vs 0%) and basal cell carcinoma (2% vs <1%).

G-Clb vs R-Clb

Ninety-four percent of patients in the G-Clb arm and 90% of those in the R-Clb arm had at least 1 AE. The rates of grade 3-5 AEs were 72% and 60%, respectively. The rates of serious AEs were 45% and 39%, respectively. The rates of fatal AEs were 7% and 10%, respectively.

Fifteen percent of patients in the G-Clb arm and 12% of those in the R-Clb arm had late-onset neutropenia. The rates of prolonged neutropenia were 2% and 4%, respectively.

Eleven percent of patients in the G-Clb arm and 10% of those in the Clb arm had second malignancies. Squamous cell carcinoma occurred in 2% of patients in both arms. Basal cell carcinoma occurred in 2% of G-Clb recipients and 1% of R-Clb recipients.

Image from NIAID

The US Food and Drug Administrated (FDA) placed a clinical hold on the phase 1 trial of the Sleeping Beauty (SB)-generated CAR T-cell therapy in relapsed or refractory leukemia and lymphoma patients.

The Sleeping Beauty platform was designed to very rapidly manufacture CD19-specific CAR T cells at the point of care.

All SB-CAR T-cell processing is planned to take place within 2 days at the healthcare facility, thus eliminating shipping cells from hospitals to production sites and back again.

The FDA is requesting more chemistry, manufacturing, and control (CMC) information before allowing the trial to proceed.

The Sleeping Beauty technology, a non-viral transposon/transposase system, has the potential to reduce the costs and complexity associated with recombinant viral vector-based immunotherapy, according to developers.

Ziopharm Oncology, Precigen, Inc, a wholly owned subsidiary of Intrexon Corporation, and the University of Texas MD Anderson Cancer Center, are developing the Sleeping Beauty CAR T cell therapy.

“We know what is needed to address the hold issues and are looking forward to responding to the agency in a timely manner,” said Laurence Cooper, MD, PhD, chief executive officer of Ziopharm, in a corporate release.

“We are undertaking cutting-edge science and are on the verge of a paradigm shift based on our approach to very rapidly manufacture CD19-specific T cells within 2 days using our non-viral approach to CAR-T therapy based on the Sleeping Beauty platform.”

The phase 1 trial in question is a third-generation trial in which the CAR T cells are designed to co-express CD19-specific CAR, membrane-bound interleukin 15, and a safety switch.

The findings from earlier generation phase 1 trials have been previously reported in The Journal of Clinical Investigation. 

Image from NIAID

The US Food and Drug Administrated (FDA) placed a clinical hold on the phase 1 trial of the Sleeping Beauty (SB)-generated CAR T-cell therapy in relapsed or refractory leukemia and lymphoma patients.

The Sleeping Beauty platform was designed to very rapidly manufacture CD19-specific CAR T cells at the point of care.

All SB-CAR T-cell processing is planned to take place within 2 days at the healthcare facility, thus eliminating shipping cells from hospitals to production sites and back again.

The FDA is requesting more chemistry, manufacturing, and control (CMC) information before allowing the trial to proceed.

The Sleeping Beauty technology, a non-viral transposon/transposase system, has the potential to reduce the costs and complexity associated with recombinant viral vector-based immunotherapy, according to developers.

Ziopharm Oncology, Precigen, Inc, a wholly owned subsidiary of Intrexon Corporation, and the University of Texas MD Anderson Cancer Center, are developing the Sleeping Beauty CAR T cell therapy.

“We know what is needed to address the hold issues and are looking forward to responding to the agency in a timely manner,” said Laurence Cooper, MD, PhD, chief executive officer of Ziopharm, in a corporate release.

“We are undertaking cutting-edge science and are on the verge of a paradigm shift based on our approach to very rapidly manufacture CD19-specific T cells within 2 days using our non-viral approach to CAR-T therapy based on the Sleeping Beauty platform.”

The phase 1 trial in question is a third-generation trial in which the CAR T cells are designed to co-express CD19-specific CAR, membrane-bound interleukin 15, and a safety switch.

The findings from earlier generation phase 1 trials have been previously reported in The Journal of Clinical Investigation. 

Image from NIAID

The US Food and Drug Administrated (FDA) placed a clinical hold on the phase 1 trial of the Sleeping Beauty (SB)-generated CAR T-cell therapy in relapsed or refractory leukemia and lymphoma patients.

The Sleeping Beauty platform was designed to very rapidly manufacture CD19-specific CAR T cells at the point of care.

All SB-CAR T-cell processing is planned to take place within 2 days at the healthcare facility, thus eliminating shipping cells from hospitals to production sites and back again.

The FDA is requesting more chemistry, manufacturing, and control (CMC) information before allowing the trial to proceed.

The Sleeping Beauty technology, a non-viral transposon/transposase system, has the potential to reduce the costs and complexity associated with recombinant viral vector-based immunotherapy, according to developers.

Ziopharm Oncology, Precigen, Inc, a wholly owned subsidiary of Intrexon Corporation, and the University of Texas MD Anderson Cancer Center, are developing the Sleeping Beauty CAR T cell therapy.

“We know what is needed to address the hold issues and are looking forward to responding to the agency in a timely manner,” said Laurence Cooper, MD, PhD, chief executive officer of Ziopharm, in a corporate release.

“We are undertaking cutting-edge science and are on the verge of a paradigm shift based on our approach to very rapidly manufacture CD19-specific T cells within 2 days using our non-viral approach to CAR-T therapy based on the Sleeping Beauty platform.”

The phase 1 trial in question is a third-generation trial in which the CAR T cells are designed to co-express CD19-specific CAR, membrane-bound interleukin 15, and a safety switch.

The findings from earlier generation phase 1 trials have been previously reported in The Journal of Clinical Investigation. 

©ASCO/Scott Morgan 2018

CHICAGO—Minimal residual disease (MRD) kinetics confirms the high, durable MRD-negativity with venetoclax plus rituximab in relapsed/refractory chronic lymphocytic leukemia (CLL), according to a further examination of the phase 3 MURANO study.

Undetectable MRD-negativity is associated with extended progression-free survival (PFS) and overall survival in patients receiving chemoimmunotherapy for CLL.

“Attainment of MRD-negativity in relapsed/refractory CLL is also a desired trial endpoint due to the subjectivity of complete response definition regarding pathologic lymph node size,” said Peter Hillmen, MD, of St James’s University Hospital, Leeds, United Kingdom, at the 2018 ASCO Annual Meeting.

Dr Hillmen reported new data on MRD response in cytogenetic and molecular risk groups, MRD sustainability and kinetics, and MRD conversion in the MURANO trial (abstract 7508).

MURANO trial (NCT02005471)

In the trial, venetoclax-rituximab showed superior PFS and peripheral blood and bone marrow MRD-negativity as compared to bendamustine plus rituximab (BR) in relapsed/refractory CLL patients.

Patients were randomized to venetoclax-rituximab for 6 months, followed by single-agent venetoclax for up to 1.5 years, or BR for 6 months. Peripheral blood samples were serially collected and bone marrow was collected at the end of combination treatment or at best response.

MRD findings

The new results show higher concordance in MRD-negativity between bone marrow and peripheral blood in venetoclax-rituximab (45 of 50 patients, 90%) vs BR (3 of 10 patients, 30%) in paired samples.

Focusing on peripheral blood MRD, Dr Hillmen said the best MRD-negativity rates were higher with venetoclax-rituximab (84%) than BR (23%). These results were independent of high-risk factors—such as del 17p, IGVH unmutated, and mutated TP53—only for venetoclax-rituximab treated patients.

“The superior peripheral blood MRD response with venetoclax-rituximab was consistent across subgroups at the end of completion of treatment,” Dr Hillmen said. “Most patients who achieved peripheral blood MRD-negativity on venetoclax-rituximab remained MRD-negative and were progression-free.”

Among 121 of 194 (62%) patients on venetoclax-rituximab who achieved MRD-negativity at the end of combination therapy, 100 (83%) patients maintained MRD-negativity and were progression-free at a median follow-up of 13.8 months. Two patients developed progressive disease and 2 patients died (unrelated to CLL).

Two patients developed Richter’s disease (with one MRD-positive directly before therapy) and 15 (12%) patients converted to confirmed MRD-positive at a median MRD-positive follow-up of 5.6 months.

“High peripheral blood MRD-negativity at the end of combination treatment and concordance with bone marrow MRD with venetoclax-rituximab,” Dr Hillmen said, “confirms the value of peripheral blood MRD for evaluation of treatment benefit in relapsed/refractory CLL patients. The high rate of peripheral blood MRD-negativity at end of combination treatment with venetoclax-rituximab was attained regardless of risk features.”

Some conversion to MRD-positivity occurred only in a small proportion of patients. Most cases were of intermediate level and remained progression-free, he said.

“MRD kinetics indicate that peripheral blood MRD-negativity with venetoclax-rituximab occurs early and is maintained over time with current follow-up,” Dr Hillmen added. The MRD data now provide a framework for designing response adaptive therapy.

The US Food and Drug Administration recently approved venetoclax-rituximab for CLL or small lymphocytic lymphoma for patients with or without del 17p.

Venetoclax is being developed by Genentech and Abbvie. 

©ASCO/Scott Morgan 2018

CHICAGO—Minimal residual disease (MRD) kinetics confirms the high, durable MRD-negativity with venetoclax plus rituximab in relapsed/refractory chronic lymphocytic leukemia (CLL), according to a further examination of the phase 3 MURANO study.

Undetectable MRD-negativity is associated with extended progression-free survival (PFS) and overall survival in patients receiving chemoimmunotherapy for CLL.

“Attainment of MRD-negativity in relapsed/refractory CLL is also a desired trial endpoint due to the subjectivity of complete response definition regarding pathologic lymph node size,” said Peter Hillmen, MD, of St James’s University Hospital, Leeds, United Kingdom, at the 2018 ASCO Annual Meeting.

Dr Hillmen reported new data on MRD response in cytogenetic and molecular risk groups, MRD sustainability and kinetics, and MRD conversion in the MURANO trial (abstract 7508).

MURANO trial (NCT02005471)

In the trial, venetoclax-rituximab showed superior PFS and peripheral blood and bone marrow MRD-negativity as compared to bendamustine plus rituximab (BR) in relapsed/refractory CLL patients.

Patients were randomized to venetoclax-rituximab for 6 months, followed by single-agent venetoclax for up to 1.5 years, or BR for 6 months. Peripheral blood samples were serially collected and bone marrow was collected at the end of combination treatment or at best response.

MRD findings

The new results show higher concordance in MRD-negativity between bone marrow and peripheral blood in venetoclax-rituximab (45 of 50 patients, 90%) vs BR (3 of 10 patients, 30%) in paired samples.

Focusing on peripheral blood MRD, Dr Hillmen said the best MRD-negativity rates were higher with venetoclax-rituximab (84%) than BR (23%). These results were independent of high-risk factors—such as del 17p, IGVH unmutated, and mutated TP53—only for venetoclax-rituximab treated patients.

“The superior peripheral blood MRD response with venetoclax-rituximab was consistent across subgroups at the end of completion of treatment,” Dr Hillmen said. “Most patients who achieved peripheral blood MRD-negativity on venetoclax-rituximab remained MRD-negative and were progression-free.”

Among 121 of 194 (62%) patients on venetoclax-rituximab who achieved MRD-negativity at the end of combination therapy, 100 (83%) patients maintained MRD-negativity and were progression-free at a median follow-up of 13.8 months. Two patients developed progressive disease and 2 patients died (unrelated to CLL).

Two patients developed Richter’s disease (with one MRD-positive directly before therapy) and 15 (12%) patients converted to confirmed MRD-positive at a median MRD-positive follow-up of 5.6 months.

“High peripheral blood MRD-negativity at the end of combination treatment and concordance with bone marrow MRD with venetoclax-rituximab,” Dr Hillmen said, “confirms the value of peripheral blood MRD for evaluation of treatment benefit in relapsed/refractory CLL patients. The high rate of peripheral blood MRD-negativity at end of combination treatment with venetoclax-rituximab was attained regardless of risk features.”

Some conversion to MRD-positivity occurred only in a small proportion of patients. Most cases were of intermediate level and remained progression-free, he said.

“MRD kinetics indicate that peripheral blood MRD-negativity with venetoclax-rituximab occurs early and is maintained over time with current follow-up,” Dr Hillmen added. The MRD data now provide a framework for designing response adaptive therapy.

The US Food and Drug Administration recently approved venetoclax-rituximab for CLL or small lymphocytic lymphoma for patients with or without del 17p.

Venetoclax is being developed by Genentech and Abbvie. 

©ASCO/Scott Morgan 2018

CHICAGO—Minimal residual disease (MRD) kinetics confirms the high, durable MRD-negativity with venetoclax plus rituximab in relapsed/refractory chronic lymphocytic leukemia (CLL), according to a further examination of the phase 3 MURANO study.

Undetectable MRD-negativity is associated with extended progression-free survival (PFS) and overall survival in patients receiving chemoimmunotherapy for CLL.

“Attainment of MRD-negativity in relapsed/refractory CLL is also a desired trial endpoint due to the subjectivity of complete response definition regarding pathologic lymph node size,” said Peter Hillmen, MD, of St James’s University Hospital, Leeds, United Kingdom, at the 2018 ASCO Annual Meeting.

Dr Hillmen reported new data on MRD response in cytogenetic and molecular risk groups, MRD sustainability and kinetics, and MRD conversion in the MURANO trial (abstract 7508).

MURANO trial (NCT02005471)

In the trial, venetoclax-rituximab showed superior PFS and peripheral blood and bone marrow MRD-negativity as compared to bendamustine plus rituximab (BR) in relapsed/refractory CLL patients.

Patients were randomized to venetoclax-rituximab for 6 months, followed by single-agent venetoclax for up to 1.5 years, or BR for 6 months. Peripheral blood samples were serially collected and bone marrow was collected at the end of combination treatment or at best response.

MRD findings

The new results show higher concordance in MRD-negativity between bone marrow and peripheral blood in venetoclax-rituximab (45 of 50 patients, 90%) vs BR (3 of 10 patients, 30%) in paired samples.

Focusing on peripheral blood MRD, Dr Hillmen said the best MRD-negativity rates were higher with venetoclax-rituximab (84%) than BR (23%). These results were independent of high-risk factors—such as del 17p, IGVH unmutated, and mutated TP53—only for venetoclax-rituximab treated patients.

“The superior peripheral blood MRD response with venetoclax-rituximab was consistent across subgroups at the end of completion of treatment,” Dr Hillmen said. “Most patients who achieved peripheral blood MRD-negativity on venetoclax-rituximab remained MRD-negative and were progression-free.”

Among 121 of 194 (62%) patients on venetoclax-rituximab who achieved MRD-negativity at the end of combination therapy, 100 (83%) patients maintained MRD-negativity and were progression-free at a median follow-up of 13.8 months. Two patients developed progressive disease and 2 patients died (unrelated to CLL).

Two patients developed Richter’s disease (with one MRD-positive directly before therapy) and 15 (12%) patients converted to confirmed MRD-positive at a median MRD-positive follow-up of 5.6 months.

“High peripheral blood MRD-negativity at the end of combination treatment and concordance with bone marrow MRD with venetoclax-rituximab,” Dr Hillmen said, “confirms the value of peripheral blood MRD for evaluation of treatment benefit in relapsed/refractory CLL patients. The high rate of peripheral blood MRD-negativity at end of combination treatment with venetoclax-rituximab was attained regardless of risk features.”

Some conversion to MRD-positivity occurred only in a small proportion of patients. Most cases were of intermediate level and remained progression-free, he said.

“MRD kinetics indicate that peripheral blood MRD-negativity with venetoclax-rituximab occurs early and is maintained over time with current follow-up,” Dr Hillmen added. The MRD data now provide a framework for designing response adaptive therapy.

The US Food and Drug Administration recently approved venetoclax-rituximab for CLL or small lymphocytic lymphoma for patients with or without del 17p.

Venetoclax is being developed by Genentech and Abbvie. 

STOCKHOLM, SWEDEN – Adding an experimental antibody-drug conjugate to bendamustine and rituximab more than doubled overall survival over bendamustine/rituximab alone in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), investigators reported.

Among 80 transplant-ineligible patients with relapsed or refractory DLBCL in a phase 2 trial, the combination of the antibody-drug conjugate (ADC) polatuzumab vedotin plus bendamustine/rituximab (BR) was associated with a 40% complete response rate, compared with 15% for BR alone.

More importantly, the ADC was associated with 6.7 months median progression-free survival (PFS) versus 2 months for BR, and 11.8 months median overall survival (OS), versus 4.7 months for BR alone, reported Laurie Sehn, MD, from BC Cancer in Vancouver, British Columbia, Canada.

“This randomized phase 2 trial really is, so far, the only head-to-head comparison of a novel targeted agent against a standard therapy in this patient population that’s ineligible for transplant, and it demonstrated that the combination polatuzumab vedotin with BR significantly improved the response rates and progression-free survival, as well as overall survival,” she said at the annual congress of the European Hematology Association.

However, in a separate cohort of patients with follicular lymphoma in the same trial, there was no difference in either PFS or OS during follow-up to date, Dr. Sehn reported.

SOURCE: Sehn LH et al. EHA Congress, Abstract S802.

STOCKHOLM, SWEDEN – Adding an experimental antibody-drug conjugate to bendamustine and rituximab more than doubled overall survival over bendamustine/rituximab alone in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), investigators reported.

Among 80 transplant-ineligible patients with relapsed or refractory DLBCL in a phase 2 trial, the combination of the antibody-drug conjugate (ADC) polatuzumab vedotin plus bendamustine/rituximab (BR) was associated with a 40% complete response rate, compared with 15% for BR alone.

More importantly, the ADC was associated with 6.7 months median progression-free survival (PFS) versus 2 months for BR, and 11.8 months median overall survival (OS), versus 4.7 months for BR alone, reported Laurie Sehn, MD, from BC Cancer in Vancouver, British Columbia, Canada.

“This randomized phase 2 trial really is, so far, the only head-to-head comparison of a novel targeted agent against a standard therapy in this patient population that’s ineligible for transplant, and it demonstrated that the combination polatuzumab vedotin with BR significantly improved the response rates and progression-free survival, as well as overall survival,” she said at the annual congress of the European Hematology Association.

However, in a separate cohort of patients with follicular lymphoma in the same trial, there was no difference in either PFS or OS during follow-up to date, Dr. Sehn reported.

SOURCE: Sehn LH et al. EHA Congress, Abstract S802.

STOCKHOLM, SWEDEN – Adding an experimental antibody-drug conjugate to bendamustine and rituximab more than doubled overall survival over bendamustine/rituximab alone in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), investigators reported.

Among 80 transplant-ineligible patients with relapsed or refractory DLBCL in a phase 2 trial, the combination of the antibody-drug conjugate (ADC) polatuzumab vedotin plus bendamustine/rituximab (BR) was associated with a 40% complete response rate, compared with 15% for BR alone.

More importantly, the ADC was associated with 6.7 months median progression-free survival (PFS) versus 2 months for BR, and 11.8 months median overall survival (OS), versus 4.7 months for BR alone, reported Laurie Sehn, MD, from BC Cancer in Vancouver, British Columbia, Canada.

“This randomized phase 2 trial really is, so far, the only head-to-head comparison of a novel targeted agent against a standard therapy in this patient population that’s ineligible for transplant, and it demonstrated that the combination polatuzumab vedotin with BR significantly improved the response rates and progression-free survival, as well as overall survival,” she said at the annual congress of the European Hematology Association.

However, in a separate cohort of patients with follicular lymphoma in the same trial, there was no difference in either PFS or OS during follow-up to date, Dr. Sehn reported.

SOURCE: Sehn LH et al. EHA Congress, Abstract S802.

follicular lymphoma

Autologous and allogeneic hematopoietic stem cell transplantation (HCT) both offer excellent long-term survival in follicular lymphoma (FL) patients who experience early treatment failure, an analysis of a large transplant registry suggests.

Five-year survival rates exceeded 70% for patients who received autologous or matched sibling donor (MSD) transplants, according to the analysis of the Center for International Blood and Marrow Transplant Research (CIBMTR) database. The database included 440 patients who underwent a procedure between 2002 and 2014.

“Until better risk-stratification tools are available for FL, auto-HCT and MSD allo-HCT should be considered as effective treatment options with excellent long-term survival for high-risk patients as defined by early treatment failure,” Sonali M. Smith, MD, of the University of Chicago, and co-investigators wrote in the journal Cancer.

Early treatment failure in FL is associated with worse overall survival. In the National LymphoCare Study (NLCS), patients who received upfront R-CHOP therapy and progressed within 24 months had a 5-year overall survival of 50%, versus 90% for patients without early progression.

By contrast, survival figures in the present study are “provocatively higher” than those in the NLCS, in which only 8 out of 110 patients underwent HCT, Dr Smith and co-authors said.

Dr Smith’s study showed that with a median follow-up of 69 to 73 months, adjusted probability of 5-year overall survival was 70% for autologous and 73% for MSD HCT, versus 49% for matched unrelated donor HCT (P=0.0008).

Ryan C. Lynch, MD, and Ajay K. Gopal, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, said that the finding “convincingly demonstrates” the benefit of transplant in the setting of early treatment failure.

“Select patients (particularly younger patients) with chemoresponsive disease who understand the risk-benefit ratio in comparison with currently approved and experimental therapies still remain good candidates for autologous HCT,” Drs Lynch and Gopal said in an editorial.

“For older patients or patients with comorbidities, we would continue to recommend clinical trials or treatment with an approved PI3K inhibitor,” they added.

The study by Dr Smith and colleagues is not the first to show a benefit of HCT in this clinical scenario. In a recent NLCS/CIBMTR analysis of FL patients, 5-year overall survival was 73% for those undergoing autologous HCT done within a year of early treatment failure, versus 60% for those who did not (P=0.05).

The two studies “collectively suggest that transplantation should be considered in this high-risk group of patients with early relapse,” Dr Smith and co-authors wrote. 

follicular lymphoma

Autologous and allogeneic hematopoietic stem cell transplantation (HCT) both offer excellent long-term survival in follicular lymphoma (FL) patients who experience early treatment failure, an analysis of a large transplant registry suggests.

Five-year survival rates exceeded 70% for patients who received autologous or matched sibling donor (MSD) transplants, according to the analysis of the Center for International Blood and Marrow Transplant Research (CIBMTR) database. The database included 440 patients who underwent a procedure between 2002 and 2014.

“Until better risk-stratification tools are available for FL, auto-HCT and MSD allo-HCT should be considered as effective treatment options with excellent long-term survival for high-risk patients as defined by early treatment failure,” Sonali M. Smith, MD, of the University of Chicago, and co-investigators wrote in the journal Cancer.

Early treatment failure in FL is associated with worse overall survival. In the National LymphoCare Study (NLCS), patients who received upfront R-CHOP therapy and progressed within 24 months had a 5-year overall survival of 50%, versus 90% for patients without early progression.

By contrast, survival figures in the present study are “provocatively higher” than those in the NLCS, in which only 8 out of 110 patients underwent HCT, Dr Smith and co-authors said.

Dr Smith’s study showed that with a median follow-up of 69 to 73 months, adjusted probability of 5-year overall survival was 70% for autologous and 73% for MSD HCT, versus 49% for matched unrelated donor HCT (P=0.0008).

Ryan C. Lynch, MD, and Ajay K. Gopal, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, said that the finding “convincingly demonstrates” the benefit of transplant in the setting of early treatment failure.

“Select patients (particularly younger patients) with chemoresponsive disease who understand the risk-benefit ratio in comparison with currently approved and experimental therapies still remain good candidates for autologous HCT,” Drs Lynch and Gopal said in an editorial.

“For older patients or patients with comorbidities, we would continue to recommend clinical trials or treatment with an approved PI3K inhibitor,” they added.

The study by Dr Smith and colleagues is not the first to show a benefit of HCT in this clinical scenario. In a recent NLCS/CIBMTR analysis of FL patients, 5-year overall survival was 73% for those undergoing autologous HCT done within a year of early treatment failure, versus 60% for those who did not (P=0.05).

The two studies “collectively suggest that transplantation should be considered in this high-risk group of patients with early relapse,” Dr Smith and co-authors wrote. 

follicular lymphoma

Autologous and allogeneic hematopoietic stem cell transplantation (HCT) both offer excellent long-term survival in follicular lymphoma (FL) patients who experience early treatment failure, an analysis of a large transplant registry suggests.

Five-year survival rates exceeded 70% for patients who received autologous or matched sibling donor (MSD) transplants, according to the analysis of the Center for International Blood and Marrow Transplant Research (CIBMTR) database. The database included 440 patients who underwent a procedure between 2002 and 2014.

“Until better risk-stratification tools are available for FL, auto-HCT and MSD allo-HCT should be considered as effective treatment options with excellent long-term survival for high-risk patients as defined by early treatment failure,” Sonali M. Smith, MD, of the University of Chicago, and co-investigators wrote in the journal Cancer.

Early treatment failure in FL is associated with worse overall survival. In the National LymphoCare Study (NLCS), patients who received upfront R-CHOP therapy and progressed within 24 months had a 5-year overall survival of 50%, versus 90% for patients without early progression.

By contrast, survival figures in the present study are “provocatively higher” than those in the NLCS, in which only 8 out of 110 patients underwent HCT, Dr Smith and co-authors said.

Dr Smith’s study showed that with a median follow-up of 69 to 73 months, adjusted probability of 5-year overall survival was 70% for autologous and 73% for MSD HCT, versus 49% for matched unrelated donor HCT (P=0.0008).

Ryan C. Lynch, MD, and Ajay K. Gopal, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, said that the finding “convincingly demonstrates” the benefit of transplant in the setting of early treatment failure.

“Select patients (particularly younger patients) with chemoresponsive disease who understand the risk-benefit ratio in comparison with currently approved and experimental therapies still remain good candidates for autologous HCT,” Drs Lynch and Gopal said in an editorial.

“For older patients or patients with comorbidities, we would continue to recommend clinical trials or treatment with an approved PI3K inhibitor,” they added.

The study by Dr Smith and colleagues is not the first to show a benefit of HCT in this clinical scenario. In a recent NLCS/CIBMTR analysis of FL patients, 5-year overall survival was 73% for those undergoing autologous HCT done within a year of early treatment failure, versus 60% for those who did not (P=0.05).

The two studies “collectively suggest that transplantation should be considered in this high-risk group of patients with early relapse,” Dr Smith and co-authors wrote. 

Micrograph showing Hodgkin lymphoma

CHICAGO—Interim PET scans can identify a subset of Hodgkin lymphoma (HL) patients with a better outcome suitable for de-escalation treatment after upfront BEACOPP without impairing disease control, according to final results of the AHL2011-LYSA study.

BEACOPP, compared to ABVD, improves progression-free survival (PFS) but not overall survival (OS) and is associated with a higher risk of myelodysplasia, acute leukemia, and infertility.

Investigators evaluated whether some patients might be able to reduce treatment intensity without compromising the effectiveness of their therapy.

Olivier Casasnovas, MD, of CHU Le Bocage Service d'Hématologie Clinique, Dijon, France,  presented the final analysis at the 2018 ASCO Annual Meeting (abstract 7503).

AHL2011-LYSA study (NCT01358747)

The randomized phase 3 study compared an early PET-driven treatment de-escalation to a non-PET-monitored strategy in patients with advanced-stage HL.

The study included 823 previously untreated patients, median age 30 years (range 16 – 60), with stage III, IV, or high-risk IIB HL.

The PET-driven strategy consisted of 2 BEACOPP* cycles (PET2), followed by 4 cycles of ABVD** for PET2-negative patients, and 4 cycles of BEACOPP for PET2-positive patients.

The experimental PET-driven strategy (410 patients) was randomly compared to a standard treatment delivering 6 cycles of BEACOPP (413 patients). PFS was the primary endpoint with a hypothesis of non-inferiority of the PET-driven arm compared to the standard arm.

Patients characteristics were well balanced between the arms, Dr Casasnovas said. PET2-positivity rate was similar in both arms (experimental 13%, standard 12%).

Based on PET2 results, 346 (84%) patients received 4 cycles of ABVD and 51 (12%) patients received 4 additional cycles of BEACOPP in the experimental arm.

Results

With a median follow-up of 50 months, the 5-year PFS was similar in the standard (86.2%) and the PET-driven arms (85.7%). The 5-year PFS for PET 2-negative/PET 4-negative patients was 90.9%, for PET 2-positive/PET4-negative patients was 75.4%, and for PET 4-positive patients was 46.5%.

The 5-year OS was similar in both arms (96.4% experimental, 95.2% standard).

The treatment toxicity was significantly higher in patients receiving 6 cycles of BEACOPP as compared to those who received 2 cycles of BEACOPP plus 4 cycles of ABVD.

Those who received more cycles of BEACOPP had more frequent grade 3 or higher adverse events than those with fewer cycles, including anemia (11% vs 2%), leukopenia (85% vs 74%), thrombocytopenia (44% vs 15%), and sepsis (7% vs 3%), as well as in serious adverse events (45% vs 28%).

“After 4 cycles of chemotherapy, it [PET positivity] identifies a subset of patients with a particularly poor outcome,” Dr Casasnovas said, “encouraging researchers to develop new treatment options in these patients.”

“PET performed after 2 cycles of BEACOPP escalation can be safely used to guide subsequent treatment,” he concluded.

“This approach allows clinicians to reduce the treatment-related immediate toxicity in most patients,” he added, “and provides similar patient outcomes compared to standard BEACOPP escalation treatment.” 

* Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone

**Adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine

Micrograph showing Hodgkin lymphoma

CHICAGO—Interim PET scans can identify a subset of Hodgkin lymphoma (HL) patients with a better outcome suitable for de-escalation treatment after upfront BEACOPP without impairing disease control, according to final results of the AHL2011-LYSA study.

BEACOPP, compared to ABVD, improves progression-free survival (PFS) but not overall survival (OS) and is associated with a higher risk of myelodysplasia, acute leukemia, and infertility.

Investigators evaluated whether some patients might be able to reduce treatment intensity without compromising the effectiveness of their therapy.

Olivier Casasnovas, MD, of CHU Le Bocage Service d'Hématologie Clinique, Dijon, France,  presented the final analysis at the 2018 ASCO Annual Meeting (abstract 7503).

AHL2011-LYSA study (NCT01358747)

The randomized phase 3 study compared an early PET-driven treatment de-escalation to a non-PET-monitored strategy in patients with advanced-stage HL.

The study included 823 previously untreated patients, median age 30 years (range 16 – 60), with stage III, IV, or high-risk IIB HL.

The PET-driven strategy consisted of 2 BEACOPP* cycles (PET2), followed by 4 cycles of ABVD** for PET2-negative patients, and 4 cycles of BEACOPP for PET2-positive patients.

The experimental PET-driven strategy (410 patients) was randomly compared to a standard treatment delivering 6 cycles of BEACOPP (413 patients). PFS was the primary endpoint with a hypothesis of non-inferiority of the PET-driven arm compared to the standard arm.

Patients characteristics were well balanced between the arms, Dr Casasnovas said. PET2-positivity rate was similar in both arms (experimental 13%, standard 12%).

Based on PET2 results, 346 (84%) patients received 4 cycles of ABVD and 51 (12%) patients received 4 additional cycles of BEACOPP in the experimental arm.

Results

With a median follow-up of 50 months, the 5-year PFS was similar in the standard (86.2%) and the PET-driven arms (85.7%). The 5-year PFS for PET 2-negative/PET 4-negative patients was 90.9%, for PET 2-positive/PET4-negative patients was 75.4%, and for PET 4-positive patients was 46.5%.

The 5-year OS was similar in both arms (96.4% experimental, 95.2% standard).

The treatment toxicity was significantly higher in patients receiving 6 cycles of BEACOPP as compared to those who received 2 cycles of BEACOPP plus 4 cycles of ABVD.

Those who received more cycles of BEACOPP had more frequent grade 3 or higher adverse events than those with fewer cycles, including anemia (11% vs 2%), leukopenia (85% vs 74%), thrombocytopenia (44% vs 15%), and sepsis (7% vs 3%), as well as in serious adverse events (45% vs 28%).

“After 4 cycles of chemotherapy, it [PET positivity] identifies a subset of patients with a particularly poor outcome,” Dr Casasnovas said, “encouraging researchers to develop new treatment options in these patients.”

“PET performed after 2 cycles of BEACOPP escalation can be safely used to guide subsequent treatment,” he concluded.

“This approach allows clinicians to reduce the treatment-related immediate toxicity in most patients,” he added, “and provides similar patient outcomes compared to standard BEACOPP escalation treatment.” 

* Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone

**Adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine

Micrograph showing Hodgkin lymphoma

CHICAGO—Interim PET scans can identify a subset of Hodgkin lymphoma (HL) patients with a better outcome suitable for de-escalation treatment after upfront BEACOPP without impairing disease control, according to final results of the AHL2011-LYSA study.

BEACOPP, compared to ABVD, improves progression-free survival (PFS) but not overall survival (OS) and is associated with a higher risk of myelodysplasia, acute leukemia, and infertility.

Investigators evaluated whether some patients might be able to reduce treatment intensity without compromising the effectiveness of their therapy.

Olivier Casasnovas, MD, of CHU Le Bocage Service d'Hématologie Clinique, Dijon, France,  presented the final analysis at the 2018 ASCO Annual Meeting (abstract 7503).

AHL2011-LYSA study (NCT01358747)

The randomized phase 3 study compared an early PET-driven treatment de-escalation to a non-PET-monitored strategy in patients with advanced-stage HL.

The study included 823 previously untreated patients, median age 30 years (range 16 – 60), with stage III, IV, or high-risk IIB HL.

The PET-driven strategy consisted of 2 BEACOPP* cycles (PET2), followed by 4 cycles of ABVD** for PET2-negative patients, and 4 cycles of BEACOPP for PET2-positive patients.

The experimental PET-driven strategy (410 patients) was randomly compared to a standard treatment delivering 6 cycles of BEACOPP (413 patients). PFS was the primary endpoint with a hypothesis of non-inferiority of the PET-driven arm compared to the standard arm.

Patients characteristics were well balanced between the arms, Dr Casasnovas said. PET2-positivity rate was similar in both arms (experimental 13%, standard 12%).

Based on PET2 results, 346 (84%) patients received 4 cycles of ABVD and 51 (12%) patients received 4 additional cycles of BEACOPP in the experimental arm.

Results

With a median follow-up of 50 months, the 5-year PFS was similar in the standard (86.2%) and the PET-driven arms (85.7%). The 5-year PFS for PET 2-negative/PET 4-negative patients was 90.9%, for PET 2-positive/PET4-negative patients was 75.4%, and for PET 4-positive patients was 46.5%.

The 5-year OS was similar in both arms (96.4% experimental, 95.2% standard).

The treatment toxicity was significantly higher in patients receiving 6 cycles of BEACOPP as compared to those who received 2 cycles of BEACOPP plus 4 cycles of ABVD.

Those who received more cycles of BEACOPP had more frequent grade 3 or higher adverse events than those with fewer cycles, including anemia (11% vs 2%), leukopenia (85% vs 74%), thrombocytopenia (44% vs 15%), and sepsis (7% vs 3%), as well as in serious adverse events (45% vs 28%).

“After 4 cycles of chemotherapy, it [PET positivity] identifies a subset of patients with a particularly poor outcome,” Dr Casasnovas said, “encouraging researchers to develop new treatment options in these patients.”

“PET performed after 2 cycles of BEACOPP escalation can be safely used to guide subsequent treatment,” he concluded.

“This approach allows clinicians to reduce the treatment-related immediate toxicity in most patients,” he added, “and provides similar patient outcomes compared to standard BEACOPP escalation treatment.” 

* Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone

**Adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine

Immunohistochemical panels used in the diagnosis of mantle cell lymphoma should include cyclin D1 and SOX11 immunostaining, according to a good practice paper from the British Society of Haematology.

Pamela McKay, MD, of the Beatson West of Scotland Cancer Centre, Glasgow, and her colleagues provided updated recommendations on diagnosis and staging of mantle cell lymphoma (MCL) based on a review of literature from 1980 to 2017. The good practice paper aims to offer best practice advice based on consensus where the evidence is limited. Specifically, the paper incorporates new information on molecular pathology and the use of positron emission tomography/computed tomography (PET/CT) scanning in staging of disease.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The top recommendations related to MCL diagnosis include performing lymph node excision or adequate core biopsy for diagnosis of nodal MCL. For non-nodal presentation, a tissue biopsy or peripheral blood can be used. Additionally, immunohistochemical panels should include cyclin D1 and SOX11 immunostaining.

In cases of atypical morphology, aberrant immunophenotype, equivocal cyclin D1 positivity, or unusual clinical presentation, the authors recommended fluorescence in situ hybridization (FISH) to demonstrate the presence of the t(11;14) translocation. They also recommended recording the Ki67 Proliferation Index at baseline, with an index of greater than 30% being indicative of a poorer outcome.

In terms of staging disease, Dr. McKay and her associates recommended that patients undergo staging with CT of the neck, chest, abdomen, and pelvis. They recommended against routine use of fluorodeoxyglucose PET for MCL staging, but said it could be considered if radical radiotherapy is being proposed for early-stage disease.

For cases with suspicion of central nervous system involvement, lumbar puncture with cytospin and immunophenotyping is recommended.

They recommended that all MCL patients have either their simplified or combined MCL international prognostic index score recorded at baseline.

All the authors made a declaration of interest to the British Society of Haematology and task force chairs, which may be viewed on request.

[email protected]

SOURCE: McKay P et al. Br J Haematol. 2018 Jun 8. doi: 10.1111/bjh.15281.

Immunohistochemical panels used in the diagnosis of mantle cell lymphoma should include cyclin D1 and SOX11 immunostaining, according to a good practice paper from the British Society of Haematology.

Pamela McKay, MD, of the Beatson West of Scotland Cancer Centre, Glasgow, and her colleagues provided updated recommendations on diagnosis and staging of mantle cell lymphoma (MCL) based on a review of literature from 1980 to 2017. The good practice paper aims to offer best practice advice based on consensus where the evidence is limited. Specifically, the paper incorporates new information on molecular pathology and the use of positron emission tomography/computed tomography (PET/CT) scanning in staging of disease.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The top recommendations related to MCL diagnosis include performing lymph node excision or adequate core biopsy for diagnosis of nodal MCL. For non-nodal presentation, a tissue biopsy or peripheral blood can be used. Additionally, immunohistochemical panels should include cyclin D1 and SOX11 immunostaining.

In cases of atypical morphology, aberrant immunophenotype, equivocal cyclin D1 positivity, or unusual clinical presentation, the authors recommended fluorescence in situ hybridization (FISH) to demonstrate the presence of the t(11;14) translocation. They also recommended recording the Ki67 Proliferation Index at baseline, with an index of greater than 30% being indicative of a poorer outcome.

In terms of staging disease, Dr. McKay and her associates recommended that patients undergo staging with CT of the neck, chest, abdomen, and pelvis. They recommended against routine use of fluorodeoxyglucose PET for MCL staging, but said it could be considered if radical radiotherapy is being proposed for early-stage disease.

For cases with suspicion of central nervous system involvement, lumbar puncture with cytospin and immunophenotyping is recommended.

They recommended that all MCL patients have either their simplified or combined MCL international prognostic index score recorded at baseline.

All the authors made a declaration of interest to the British Society of Haematology and task force chairs, which may be viewed on request.

[email protected]

SOURCE: McKay P et al. Br J Haematol. 2018 Jun 8. doi: 10.1111/bjh.15281.

Immunohistochemical panels used in the diagnosis of mantle cell lymphoma should include cyclin D1 and SOX11 immunostaining, according to a good practice paper from the British Society of Haematology.

Pamela McKay, MD, of the Beatson West of Scotland Cancer Centre, Glasgow, and her colleagues provided updated recommendations on diagnosis and staging of mantle cell lymphoma (MCL) based on a review of literature from 1980 to 2017. The good practice paper aims to offer best practice advice based on consensus where the evidence is limited. Specifically, the paper incorporates new information on molecular pathology and the use of positron emission tomography/computed tomography (PET/CT) scanning in staging of disease.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The top recommendations related to MCL diagnosis include performing lymph node excision or adequate core biopsy for diagnosis of nodal MCL. For non-nodal presentation, a tissue biopsy or peripheral blood can be used. Additionally, immunohistochemical panels should include cyclin D1 and SOX11 immunostaining.

In cases of atypical morphology, aberrant immunophenotype, equivocal cyclin D1 positivity, or unusual clinical presentation, the authors recommended fluorescence in situ hybridization (FISH) to demonstrate the presence of the t(11;14) translocation. They also recommended recording the Ki67 Proliferation Index at baseline, with an index of greater than 30% being indicative of a poorer outcome.

In terms of staging disease, Dr. McKay and her associates recommended that patients undergo staging with CT of the neck, chest, abdomen, and pelvis. They recommended against routine use of fluorodeoxyglucose PET for MCL staging, but said it could be considered if radical radiotherapy is being proposed for early-stage disease.

For cases with suspicion of central nervous system involvement, lumbar puncture with cytospin and immunophenotyping is recommended.

They recommended that all MCL patients have either their simplified or combined MCL international prognostic index score recorded at baseline.

All the authors made a declaration of interest to the British Society of Haematology and task force chairs, which may be viewed on request.

[email protected]

SOURCE: McKay P et al. Br J Haematol. 2018 Jun 8. doi: 10.1111/bjh.15281.

The immune checkpoint inhibitor pembrolizumab (Keytruda) has been approved for the treatment of relapsed or refractory primary mediastinal large B-cell lymphoma in adult and pediatric patients.

The Food and Drug Administration based the accelerated approval on results from 53 patients with relapsed or refractory primary mediastinal large B-cell lymphoma in the KEYNOTE-170 trial. In the phase 2 trial, patients received 200 mg of pembrolizumab intravenously for 3 weeks until unacceptable toxicity or documented disease progression occurred. This continued for up to 24 months in patients who did not display progression. The overall response rate to pembrolizumab was 45% (95% CI, 32-60), which included both complete (11%) and partial (34%) responses. The median duration of response was not met within the follow-up period (median, 9.7 months) and the median time to first objective response was 2.8 months.

The recommended dose for pembrolizumab in adults is 200 mg every 3 weeks. It is recommended that pediatric patients receive 2 mg/kg every 3 weeks, with a maximum dose of 200 mg.

The most common adverse reactions to pembrolizumab were musculoskeletal pain, upper respiratory tract infection, pyrexia, fatigue, cough, dyspnea, diarrhea, nausea, arrhythmia, and headache. In total, a quarter of patients with adverse reactions required systemic treatment with a corticosteroid and 26% of patients had serious adverse reactions.

Pembrolizumab was approved via the FDA’s accelerated approval process, which allows for earlier approval of drugs that treat serious medical conditions and fulfill an unmet medical need. The drug was approved based on tumor response rate and durability of response, the FDA noted.

[email protected]

The immune checkpoint inhibitor pembrolizumab (Keytruda) has been approved for the treatment of relapsed or refractory primary mediastinal large B-cell lymphoma in adult and pediatric patients.

The Food and Drug Administration based the accelerated approval on results from 53 patients with relapsed or refractory primary mediastinal large B-cell lymphoma in the KEYNOTE-170 trial. In the phase 2 trial, patients received 200 mg of pembrolizumab intravenously for 3 weeks until unacceptable toxicity or documented disease progression occurred. This continued for up to 24 months in patients who did not display progression. The overall response rate to pembrolizumab was 45% (95% CI, 32-60), which included both complete (11%) and partial (34%) responses. The median duration of response was not met within the follow-up period (median, 9.7 months) and the median time to first objective response was 2.8 months.

The recommended dose for pembrolizumab in adults is 200 mg every 3 weeks. It is recommended that pediatric patients receive 2 mg/kg every 3 weeks, with a maximum dose of 200 mg.

The most common adverse reactions to pembrolizumab were musculoskeletal pain, upper respiratory tract infection, pyrexia, fatigue, cough, dyspnea, diarrhea, nausea, arrhythmia, and headache. In total, a quarter of patients with adverse reactions required systemic treatment with a corticosteroid and 26% of patients had serious adverse reactions.

Pembrolizumab was approved via the FDA’s accelerated approval process, which allows for earlier approval of drugs that treat serious medical conditions and fulfill an unmet medical need. The drug was approved based on tumor response rate and durability of response, the FDA noted.

[email protected]

The immune checkpoint inhibitor pembrolizumab (Keytruda) has been approved for the treatment of relapsed or refractory primary mediastinal large B-cell lymphoma in adult and pediatric patients.

The Food and Drug Administration based the accelerated approval on results from 53 patients with relapsed or refractory primary mediastinal large B-cell lymphoma in the KEYNOTE-170 trial. In the phase 2 trial, patients received 200 mg of pembrolizumab intravenously for 3 weeks until unacceptable toxicity or documented disease progression occurred. This continued for up to 24 months in patients who did not display progression. The overall response rate to pembrolizumab was 45% (95% CI, 32-60), which included both complete (11%) and partial (34%) responses. The median duration of response was not met within the follow-up period (median, 9.7 months) and the median time to first objective response was 2.8 months.

The recommended dose for pembrolizumab in adults is 200 mg every 3 weeks. It is recommended that pediatric patients receive 2 mg/kg every 3 weeks, with a maximum dose of 200 mg.

The most common adverse reactions to pembrolizumab were musculoskeletal pain, upper respiratory tract infection, pyrexia, fatigue, cough, dyspnea, diarrhea, nausea, arrhythmia, and headache. In total, a quarter of patients with adverse reactions required systemic treatment with a corticosteroid and 26% of patients had serious adverse reactions.

Pembrolizumab was approved via the FDA’s accelerated approval process, which allows for earlier approval of drugs that treat serious medical conditions and fulfill an unmet medical need. The drug was approved based on tumor response rate and durability of response, the FDA noted.

[email protected]

Photo courtesy of Merck

The US Food and Drug Administration (FDA) granted accelerated approval to the anti-PD-1 therapy pembrolizumab (Keytruda) for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL).

The indication also includes patients who have relapsed after 2 or more prior lines of therapy.

Pembrolizumab had received priority review for PMBCL late last year and also has orphan drug designation and breakthrough therapy designation for this indication.

The FDA based its approval on data from the KEYNOTE-170 (NCT02576990 ) trial.

Investigators enrolled 53 patients onto the multicenter, open-label, single-arm trial. Patients received pembrolizumab 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression.

Patients whose disease did not progress received the drug for up to 24 months.

Patient characteristics

Patients were a median age of 33 years (range, 20 – 61), 43% were male, 92% white, 43% had an ECOG performance status of 0, and 57% had an ECOG performance status of 1.

Almost half (49%) had relapsed disease, and 36% had primary refractory disease.

About a quarter (26%) had undergone prior autologous hematopoietic stem cell transplant, and 32% had prior radiation therapy.

All patients had received prior rituximab.

Results

At a median follow-up of 9.7 months, the overall response rate was 45% (24 responders), including 11% complete responses and 34% partial responses.

The median duration of response was not reached during the follow-up period and ranged from a median 1.1 to 19.2 months.

Median time to first objective response was 2.8 months (range, 2.1 – 8.5). Accordingly, investigators do not recommend pembrolizumab for PMBCL patients who require urgent cytoreductive therapy.

Safety

The most common adverse events occurring in 10% or more of patients were musculoskeletal pain (30%), upper respiratory tract infection (28%), pyrexia (28%), fatigue (23%), cough (26%), dyspnea (21%), diarrhea (13%), abdominal pain (13%), nausea (11%), arrhythmia (11%), and headache (11%).

Eight percent of patients discontinued treatment, and 15% interrupted treatment due to adverse reactions.

Adverse events requiring systemic corticosteroid therapy occurred in 25% of patients.

Serious adverse events occurred in 26% and included arrhythmia (4 %), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%).

Six (11%) patients died within 30 days of start of treatment.

The recommended pembrolizumab dose for treatment of adults with PMBCL is 200 mg every 3 weeks.  The recommended dose in pediatric patients is 2 mg/kg (up to a maximum of 200 mg) every 3 weeks.

Additional indications for pembrolizumab include melanoma, non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, microsatellite instability-high cancer, gastric cancer, and cervical cancer.

The full prescribing information is available on the FDA website.

Pembrolizumab (Keytruda) is a product of Merck & Co, Inc. 

Photo courtesy of Merck

The US Food and Drug Administration (FDA) granted accelerated approval to the anti-PD-1 therapy pembrolizumab (Keytruda) for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL).

The indication also includes patients who have relapsed after 2 or more prior lines of therapy.

Pembrolizumab had received priority review for PMBCL late last year and also has orphan drug designation and breakthrough therapy designation for this indication.

The FDA based its approval on data from the KEYNOTE-170 (NCT02576990 ) trial.

Investigators enrolled 53 patients onto the multicenter, open-label, single-arm trial. Patients received pembrolizumab 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression.

Patients whose disease did not progress received the drug for up to 24 months.

Patient characteristics

Patients were a median age of 33 years (range, 20 – 61), 43% were male, 92% white, 43% had an ECOG performance status of 0, and 57% had an ECOG performance status of 1.

Almost half (49%) had relapsed disease, and 36% had primary refractory disease.

About a quarter (26%) had undergone prior autologous hematopoietic stem cell transplant, and 32% had prior radiation therapy.

All patients had received prior rituximab.

Results

At a median follow-up of 9.7 months, the overall response rate was 45% (24 responders), including 11% complete responses and 34% partial responses.

The median duration of response was not reached during the follow-up period and ranged from a median 1.1 to 19.2 months.

Median time to first objective response was 2.8 months (range, 2.1 – 8.5). Accordingly, investigators do not recommend pembrolizumab for PMBCL patients who require urgent cytoreductive therapy.

Safety

The most common adverse events occurring in 10% or more of patients were musculoskeletal pain (30%), upper respiratory tract infection (28%), pyrexia (28%), fatigue (23%), cough (26%), dyspnea (21%), diarrhea (13%), abdominal pain (13%), nausea (11%), arrhythmia (11%), and headache (11%).

Eight percent of patients discontinued treatment, and 15% interrupted treatment due to adverse reactions.

Adverse events requiring systemic corticosteroid therapy occurred in 25% of patients.

Serious adverse events occurred in 26% and included arrhythmia (4 %), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%).

Six (11%) patients died within 30 days of start of treatment.

The recommended pembrolizumab dose for treatment of adults with PMBCL is 200 mg every 3 weeks.  The recommended dose in pediatric patients is 2 mg/kg (up to a maximum of 200 mg) every 3 weeks.

Additional indications for pembrolizumab include melanoma, non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, microsatellite instability-high cancer, gastric cancer, and cervical cancer.

The full prescribing information is available on the FDA website.

Pembrolizumab (Keytruda) is a product of Merck & Co, Inc. 

Photo courtesy of Merck

The US Food and Drug Administration (FDA) granted accelerated approval to the anti-PD-1 therapy pembrolizumab (Keytruda) for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL).

The indication also includes patients who have relapsed after 2 or more prior lines of therapy.

Pembrolizumab had received priority review for PMBCL late last year and also has orphan drug designation and breakthrough therapy designation for this indication.

The FDA based its approval on data from the KEYNOTE-170 (NCT02576990 ) trial.

Investigators enrolled 53 patients onto the multicenter, open-label, single-arm trial. Patients received pembrolizumab 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression.

Patients whose disease did not progress received the drug for up to 24 months.

Patient characteristics

Patients were a median age of 33 years (range, 20 – 61), 43% were male, 92% white, 43% had an ECOG performance status of 0, and 57% had an ECOG performance status of 1.

Almost half (49%) had relapsed disease, and 36% had primary refractory disease.

About a quarter (26%) had undergone prior autologous hematopoietic stem cell transplant, and 32% had prior radiation therapy.

All patients had received prior rituximab.

Results

At a median follow-up of 9.7 months, the overall response rate was 45% (24 responders), including 11% complete responses and 34% partial responses.

The median duration of response was not reached during the follow-up period and ranged from a median 1.1 to 19.2 months.

Median time to first objective response was 2.8 months (range, 2.1 – 8.5). Accordingly, investigators do not recommend pembrolizumab for PMBCL patients who require urgent cytoreductive therapy.

Safety

The most common adverse events occurring in 10% or more of patients were musculoskeletal pain (30%), upper respiratory tract infection (28%), pyrexia (28%), fatigue (23%), cough (26%), dyspnea (21%), diarrhea (13%), abdominal pain (13%), nausea (11%), arrhythmia (11%), and headache (11%).

Eight percent of patients discontinued treatment, and 15% interrupted treatment due to adverse reactions.

Adverse events requiring systemic corticosteroid therapy occurred in 25% of patients.

Serious adverse events occurred in 26% and included arrhythmia (4 %), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%).

Six (11%) patients died within 30 days of start of treatment.

The recommended pembrolizumab dose for treatment of adults with PMBCL is 200 mg every 3 weeks.  The recommended dose in pediatric patients is 2 mg/kg (up to a maximum of 200 mg) every 3 weeks.

Additional indications for pembrolizumab include melanoma, non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, microsatellite instability-high cancer, gastric cancer, and cervical cancer.

The full prescribing information is available on the FDA website.

Pembrolizumab (Keytruda) is a product of Merck & Co, Inc.