CHECKMATE 205: A PHASE 2 STUDY OF NIVOLUMAB IN PATIENTS WITH CLASSICAL HODGKIN LYMPHOMA FOLLOWING AUTOLOGOUS STEM CELL TRANSPLANTATION AND BRENTUXIMAB VEDOTIN
(Abstract release date: 05/19/16)
EHA Library. Younes A. 06/12/16; 135287; S793
Dr. Anas Younes
Contributions
Contributions
Abstract
Abstract: S793
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:00 - 08:15
Location: Hall A2
Background
Classical Hodgkin lymphoma (cHL) is characterized by Hodgkin Reed–Sternberg cells, which contain genetic aberrations at 9p24.1 leading to overexpression of the programmed death receptor-1 (PD-1) ligands PD-L1 and PD-L2. Thus, cHL may be uniquely sensitive to PD-1 blockade. Nivolumab (Nivo) is a fully human IgG4 immune checkpoint inhibitor antibody targeting PD-1 that showed promising results in a phase 1b study (NCT01592370) in patients (pts) with relapsed/refractory cHL (Ansell SM et al. NEJM 2015;372:311–9) who currently have limited treatment options.
Aims
This study, Cohort B of the phase 2 Checkmate 205 study (NCT02181738), evaluated the efficacy and safety of nivo in pts with cHL who had received brentuximab vedotin (BV) after failed autologous stem cell transplantation (ASCT).
Methods
Nivo was given at 3 mg/kg IV every 2 weeks (wk). Response was assessed using 2007 IWG criteria, by both an independent radiologic review committee (IRRC) and investigators (Inv). The primary endpoint was IRRC-assessed objective response rate (ORR). Quality of life was assessed by EQ-5D VAS (0–100 scale) and EORTC QLQ-C30. Written informed consent was obtained for all pts. Results of the primary ORR analysis after approximately 6 months (mo) minimum follow-up are reported.
Results
Among 80 pts enrolled and treated, the main characteristics included median (range) age, 37 years (18–72) and median (range), 4 prior regimens (3–15). 33 pts enrolled from Europe; 47 were from the US or Canada. At data cut-off (October 2015), 51 pts (64%) remained on therapy. Of 29 pts (36%) who discontinued, the most common reason was disease progression (n=13). Only 4 pts discontinued due to an AE. 90% of pts had drug-related AEs, including 25% Grade 3–4 AEs and 1% Grade 5 (multi-organ failure). The most common drug-related AEs were fatigue (25%), infusion reaction (20%), and rash (16%). The most common serious AEs were pyrexia, tumor progression, arrhythmia, infusion reaction, septic meningitis, and pneumonia (≤4% each). Most common immune-mediated AEs were hypothyroidism/thyroiditis (14%), rash (10%), and hypersensitivity (6%). All 6 pts who stopped nivo and received subsequent stem cell transplant were alive at data cut-off. After median (range) follow-up of 8.9 mo (1.9–11.7), IRRC ORR (95% CI) was 66% (54.8%, 76.4%); CR and PR rates were 8.8% (3.6%, 17.2%) and 57.5% (45.9%, 68.5%), respectively. Almost all pts had some degree of tumor regression (Figure). All but one responder had tumor reduction of ≥50% from baseline; the other had response determined by negative FDG-PET scan. In 43 pts who had no response (SD or PD) to BV, nivo treatment resulted in IRRC ORR of 72% (31/43). Median (range) time to response was 2.1 mo (1.6–5.7). Inv ORR (95% CI) was 73% (61.4%, 81.9%); CR and PR rates were 27.5% (18.1%, 38.6%) and 45.0% (33.8%, 56.5%), respectively. At data cut-off, 62% (33/53) of IRRC responders remained in response. IRRC 6-mo PFS was 77%; OS was 99%. Mean EQ-5D VAS score increased over time, from 62 at baseline to 80 at Wk 33, with a clinically meaningful improvement in health state by Wk 9 (>7-point change). EORTC QLQ-C30 findings suggested a trend towards improvement in functional, symptom, and global health scores.
Conclusion
In pts with cHL who progressed following ASCT and BV, nivo is associated with a high response rate, long-lasting responses, and an acceptable safety profile. PFS and OS are encouraging in this heavily pretreated population. Patient reported outcomes suggest improvement in quality of life while on nivo treatment.
Session topic: Relapsed Hodgkin Lymphoma & Primary Mediastinal Large B-Cell Lymphoma (PM-DLBCL)
Keyword(s): Cancer immunotherapy, Hodgkin's lymphoma, Phase II, Tumor immunology
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:00 - 08:15
Location: Hall A2
Background
Classical Hodgkin lymphoma (cHL) is characterized by Hodgkin Reed–Sternberg cells, which contain genetic aberrations at 9p24.1 leading to overexpression of the programmed death receptor-1 (PD-1) ligands PD-L1 and PD-L2. Thus, cHL may be uniquely sensitive to PD-1 blockade. Nivolumab (Nivo) is a fully human IgG4 immune checkpoint inhibitor antibody targeting PD-1 that showed promising results in a phase 1b study (NCT01592370) in patients (pts) with relapsed/refractory cHL (Ansell SM et al. NEJM 2015;372:311–9) who currently have limited treatment options.
Aims
This study, Cohort B of the phase 2 Checkmate 205 study (NCT02181738), evaluated the efficacy and safety of nivo in pts with cHL who had received brentuximab vedotin (BV) after failed autologous stem cell transplantation (ASCT).
Methods
Nivo was given at 3 mg/kg IV every 2 weeks (wk). Response was assessed using 2007 IWG criteria, by both an independent radiologic review committee (IRRC) and investigators (Inv). The primary endpoint was IRRC-assessed objective response rate (ORR). Quality of life was assessed by EQ-5D VAS (0–100 scale) and EORTC QLQ-C30. Written informed consent was obtained for all pts. Results of the primary ORR analysis after approximately 6 months (mo) minimum follow-up are reported.
Results
Among 80 pts enrolled and treated, the main characteristics included median (range) age, 37 years (18–72) and median (range), 4 prior regimens (3–15). 33 pts enrolled from Europe; 47 were from the US or Canada. At data cut-off (October 2015), 51 pts (64%) remained on therapy. Of 29 pts (36%) who discontinued, the most common reason was disease progression (n=13). Only 4 pts discontinued due to an AE. 90% of pts had drug-related AEs, including 25% Grade 3–4 AEs and 1% Grade 5 (multi-organ failure). The most common drug-related AEs were fatigue (25%), infusion reaction (20%), and rash (16%). The most common serious AEs were pyrexia, tumor progression, arrhythmia, infusion reaction, septic meningitis, and pneumonia (≤4% each). Most common immune-mediated AEs were hypothyroidism/thyroiditis (14%), rash (10%), and hypersensitivity (6%). All 6 pts who stopped nivo and received subsequent stem cell transplant were alive at data cut-off. After median (range) follow-up of 8.9 mo (1.9–11.7), IRRC ORR (95% CI) was 66% (54.8%, 76.4%); CR and PR rates were 8.8% (3.6%, 17.2%) and 57.5% (45.9%, 68.5%), respectively. Almost all pts had some degree of tumor regression (Figure). All but one responder had tumor reduction of ≥50% from baseline; the other had response determined by negative FDG-PET scan. In 43 pts who had no response (SD or PD) to BV, nivo treatment resulted in IRRC ORR of 72% (31/43). Median (range) time to response was 2.1 mo (1.6–5.7). Inv ORR (95% CI) was 73% (61.4%, 81.9%); CR and PR rates were 27.5% (18.1%, 38.6%) and 45.0% (33.8%, 56.5%), respectively. At data cut-off, 62% (33/53) of IRRC responders remained in response. IRRC 6-mo PFS was 77%; OS was 99%. Mean EQ-5D VAS score increased over time, from 62 at baseline to 80 at Wk 33, with a clinically meaningful improvement in health state by Wk 9 (>7-point change). EORTC QLQ-C30 findings suggested a trend towards improvement in functional, symptom, and global health scores.
Conclusion
In pts with cHL who progressed following ASCT and BV, nivo is associated with a high response rate, long-lasting responses, and an acceptable safety profile. PFS and OS are encouraging in this heavily pretreated population. Patient reported outcomes suggest improvement in quality of life while on nivo treatment.
Session topic: Relapsed Hodgkin Lymphoma & Primary Mediastinal Large B-Cell Lymphoma (PM-DLBCL)
Keyword(s): Cancer immunotherapy, Hodgkin's lymphoma, Phase II, Tumor immunology
Abstract: S793
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:00 - 08:15
Location: Hall A2
Background
Classical Hodgkin lymphoma (cHL) is characterized by Hodgkin Reed–Sternberg cells, which contain genetic aberrations at 9p24.1 leading to overexpression of the programmed death receptor-1 (PD-1) ligands PD-L1 and PD-L2. Thus, cHL may be uniquely sensitive to PD-1 blockade. Nivolumab (Nivo) is a fully human IgG4 immune checkpoint inhibitor antibody targeting PD-1 that showed promising results in a phase 1b study (NCT01592370) in patients (pts) with relapsed/refractory cHL (Ansell SM et al. NEJM 2015;372:311–9) who currently have limited treatment options.
Aims
This study, Cohort B of the phase 2 Checkmate 205 study (NCT02181738), evaluated the efficacy and safety of nivo in pts with cHL who had received brentuximab vedotin (BV) after failed autologous stem cell transplantation (ASCT).
Methods
Nivo was given at 3 mg/kg IV every 2 weeks (wk). Response was assessed using 2007 IWG criteria, by both an independent radiologic review committee (IRRC) and investigators (Inv). The primary endpoint was IRRC-assessed objective response rate (ORR). Quality of life was assessed by EQ-5D VAS (0–100 scale) and EORTC QLQ-C30. Written informed consent was obtained for all pts. Results of the primary ORR analysis after approximately 6 months (mo) minimum follow-up are reported.
Results
Among 80 pts enrolled and treated, the main characteristics included median (range) age, 37 years (18–72) and median (range), 4 prior regimens (3–15). 33 pts enrolled from Europe; 47 were from the US or Canada. At data cut-off (October 2015), 51 pts (64%) remained on therapy. Of 29 pts (36%) who discontinued, the most common reason was disease progression (n=13). Only 4 pts discontinued due to an AE. 90% of pts had drug-related AEs, including 25% Grade 3–4 AEs and 1% Grade 5 (multi-organ failure). The most common drug-related AEs were fatigue (25%), infusion reaction (20%), and rash (16%). The most common serious AEs were pyrexia, tumor progression, arrhythmia, infusion reaction, septic meningitis, and pneumonia (≤4% each). Most common immune-mediated AEs were hypothyroidism/thyroiditis (14%), rash (10%), and hypersensitivity (6%). All 6 pts who stopped nivo and received subsequent stem cell transplant were alive at data cut-off. After median (range) follow-up of 8.9 mo (1.9–11.7), IRRC ORR (95% CI) was 66% (54.8%, 76.4%); CR and PR rates were 8.8% (3.6%, 17.2%) and 57.5% (45.9%, 68.5%), respectively. Almost all pts had some degree of tumor regression (Figure). All but one responder had tumor reduction of ≥50% from baseline; the other had response determined by negative FDG-PET scan. In 43 pts who had no response (SD or PD) to BV, nivo treatment resulted in IRRC ORR of 72% (31/43). Median (range) time to response was 2.1 mo (1.6–5.7). Inv ORR (95% CI) was 73% (61.4%, 81.9%); CR and PR rates were 27.5% (18.1%, 38.6%) and 45.0% (33.8%, 56.5%), respectively. At data cut-off, 62% (33/53) of IRRC responders remained in response. IRRC 6-mo PFS was 77%; OS was 99%. Mean EQ-5D VAS score increased over time, from 62 at baseline to 80 at Wk 33, with a clinically meaningful improvement in health state by Wk 9 (>7-point change). EORTC QLQ-C30 findings suggested a trend towards improvement in functional, symptom, and global health scores.
Conclusion
In pts with cHL who progressed following ASCT and BV, nivo is associated with a high response rate, long-lasting responses, and an acceptable safety profile. PFS and OS are encouraging in this heavily pretreated population. Patient reported outcomes suggest improvement in quality of life while on nivo treatment.
Session topic: Relapsed Hodgkin Lymphoma & Primary Mediastinal Large B-Cell Lymphoma (PM-DLBCL)
Keyword(s): Cancer immunotherapy, Hodgkin's lymphoma, Phase II, Tumor immunology
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:00 - 08:15
Location: Hall A2
Background
Classical Hodgkin lymphoma (cHL) is characterized by Hodgkin Reed–Sternberg cells, which contain genetic aberrations at 9p24.1 leading to overexpression of the programmed death receptor-1 (PD-1) ligands PD-L1 and PD-L2. Thus, cHL may be uniquely sensitive to PD-1 blockade. Nivolumab (Nivo) is a fully human IgG4 immune checkpoint inhibitor antibody targeting PD-1 that showed promising results in a phase 1b study (NCT01592370) in patients (pts) with relapsed/refractory cHL (Ansell SM et al. NEJM 2015;372:311–9) who currently have limited treatment options.
Aims
This study, Cohort B of the phase 2 Checkmate 205 study (NCT02181738), evaluated the efficacy and safety of nivo in pts with cHL who had received brentuximab vedotin (BV) after failed autologous stem cell transplantation (ASCT).
Methods
Nivo was given at 3 mg/kg IV every 2 weeks (wk). Response was assessed using 2007 IWG criteria, by both an independent radiologic review committee (IRRC) and investigators (Inv). The primary endpoint was IRRC-assessed objective response rate (ORR). Quality of life was assessed by EQ-5D VAS (0–100 scale) and EORTC QLQ-C30. Written informed consent was obtained for all pts. Results of the primary ORR analysis after approximately 6 months (mo) minimum follow-up are reported.
Results
Among 80 pts enrolled and treated, the main characteristics included median (range) age, 37 years (18–72) and median (range), 4 prior regimens (3–15). 33 pts enrolled from Europe; 47 were from the US or Canada. At data cut-off (October 2015), 51 pts (64%) remained on therapy. Of 29 pts (36%) who discontinued, the most common reason was disease progression (n=13). Only 4 pts discontinued due to an AE. 90% of pts had drug-related AEs, including 25% Grade 3–4 AEs and 1% Grade 5 (multi-organ failure). The most common drug-related AEs were fatigue (25%), infusion reaction (20%), and rash (16%). The most common serious AEs were pyrexia, tumor progression, arrhythmia, infusion reaction, septic meningitis, and pneumonia (≤4% each). Most common immune-mediated AEs were hypothyroidism/thyroiditis (14%), rash (10%), and hypersensitivity (6%). All 6 pts who stopped nivo and received subsequent stem cell transplant were alive at data cut-off. After median (range) follow-up of 8.9 mo (1.9–11.7), IRRC ORR (95% CI) was 66% (54.8%, 76.4%); CR and PR rates were 8.8% (3.6%, 17.2%) and 57.5% (45.9%, 68.5%), respectively. Almost all pts had some degree of tumor regression (Figure). All but one responder had tumor reduction of ≥50% from baseline; the other had response determined by negative FDG-PET scan. In 43 pts who had no response (SD or PD) to BV, nivo treatment resulted in IRRC ORR of 72% (31/43). Median (range) time to response was 2.1 mo (1.6–5.7). Inv ORR (95% CI) was 73% (61.4%, 81.9%); CR and PR rates were 27.5% (18.1%, 38.6%) and 45.0% (33.8%, 56.5%), respectively. At data cut-off, 62% (33/53) of IRRC responders remained in response. IRRC 6-mo PFS was 77%; OS was 99%. Mean EQ-5D VAS score increased over time, from 62 at baseline to 80 at Wk 33, with a clinically meaningful improvement in health state by Wk 9 (>7-point change). EORTC QLQ-C30 findings suggested a trend towards improvement in functional, symptom, and global health scores.
Conclusion
In pts with cHL who progressed following ASCT and BV, nivo is associated with a high response rate, long-lasting responses, and an acceptable safety profile. PFS and OS are encouraging in this heavily pretreated population. Patient reported outcomes suggest improvement in quality of life while on nivo treatment.
Session topic: Relapsed Hodgkin Lymphoma & Primary Mediastinal Large B-Cell Lymphoma (PM-DLBCL)
Keyword(s): Cancer immunotherapy, Hodgkin's lymphoma, Phase II, Tumor immunology
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