Selected studies of checkpoint inhibitors in lymphoma
| Checkpoint inhibitor . | Target . | Study phase . | Patient population . | Outcome(s) . |
|---|---|---|---|---|
| Nivolumab | PD-1 | II24 | R/R HL after ASCT failure | Nivolumab monotherapy |
| ORR of 69%, CR rate of 40% CRs | ||||
| Median DoR of 16.6 mo | ||||
| Median PFS of 14.7 mo | ||||
| Grade 3-4 drug-related AEs: lipase increases (5%), neutropenia (3%), ALT increases (3%) | ||||
| I/II27 | R/R HL | Nivolumab with BV | ||
| ORR of 82%, CR rate of 61% | ||||
| AEs: 98%, mostly grades 1-2, IRRs in 44% | ||||
| I/II26 | R/R HL | Nivolumab with BV | ||
| AEs: grade 3 or higher TRAEs in 16%, grade 5 in 1.5% | ||||
| ORR of 89%, CR rate of 61% | ||||
| Median PFS not reached, with median follow-up of 2.4 y | ||||
| Pembrolizumab | PD-1 | II23 | R/R HL | Pembrolizumab monotherapy |
| ORR of 69%, CR rate of 22.4% | ||||
| Response lasting 6 mo or longer in 75.6% | ||||
| TRAEs: hypothyroidism (12.4%), pyrexia (10.5%) | ||||
| AEs: immune-mediated AEs and IRRs in 28.6% | ||||
| III25 | R/R HL | Median PFS: 13.2 (pembrolizumab) vs 8.3 mo (BV) | ||
| ORR: 65.6% vs 54.2% | ||||
| CR rate: 24.5% vs 24.2% | ||||
| Median time to response: 2.8 vs 2.8 mo | ||||
| Median DoR: 20.7 vs 13.8 mo | ||||
| Grade 3-5 TRAEs: 19.6% vs 25% | ||||
| II29 | R/R PMBCL | Pembrolizumab monotherapy | ||
| ORR of 45%, CR rate of 13% | ||||
| Median DoR not reached with median follow-up of 12.5 mo | ||||
| Grade 3-4 TRAEs: 23% | ||||
| II31 | R/R MF and SS | Pembrolizumab monotherapy | ||
| ORR of 38% | ||||
| Median DoR not reached, with median follow-up of 58 wk | ||||
| Immune-related AEs leading to treatment discontinuation in 4 patients | ||||
| Nivolumab + BV +/− ipilimumab | PD-1, CD30, CTLA-4 | I/II26 | R/R HL | Ipilimumab with BV |
| AEs: grade 3 or higher TRAEs in 43%, no grade 5 | ||||
| ORR of 76%, CR rate of 57% | ||||
| Median PFS 1.2 y, with median follow-up of 2.6 y | ||||
| I/II26 | R/R HL | Ipilimumab with nivolumab and BV | ||
| AEs: grade 3 or higher TRAEs in 50%, grade 5 in 1.5% | ||||
| ORR of 82%, CR rate of 73% | ||||
| Median PFS not reached, with median follow-up of 1.7 y |
| Checkpoint inhibitor . | Target . | Study phase . | Patient population . | Outcome(s) . |
|---|---|---|---|---|
| Nivolumab | PD-1 | II24 | R/R HL after ASCT failure | Nivolumab monotherapy |
| ORR of 69%, CR rate of 40% CRs | ||||
| Median DoR of 16.6 mo | ||||
| Median PFS of 14.7 mo | ||||
| Grade 3-4 drug-related AEs: lipase increases (5%), neutropenia (3%), ALT increases (3%) | ||||
| I/II27 | R/R HL | Nivolumab with BV | ||
| ORR of 82%, CR rate of 61% | ||||
| AEs: 98%, mostly grades 1-2, IRRs in 44% | ||||
| I/II26 | R/R HL | Nivolumab with BV | ||
| AEs: grade 3 or higher TRAEs in 16%, grade 5 in 1.5% | ||||
| ORR of 89%, CR rate of 61% | ||||
| Median PFS not reached, with median follow-up of 2.4 y | ||||
| Pembrolizumab | PD-1 | II23 | R/R HL | Pembrolizumab monotherapy |
| ORR of 69%, CR rate of 22.4% | ||||
| Response lasting 6 mo or longer in 75.6% | ||||
| TRAEs: hypothyroidism (12.4%), pyrexia (10.5%) | ||||
| AEs: immune-mediated AEs and IRRs in 28.6% | ||||
| III25 | R/R HL | Median PFS: 13.2 (pembrolizumab) vs 8.3 mo (BV) | ||
| ORR: 65.6% vs 54.2% | ||||
| CR rate: 24.5% vs 24.2% | ||||
| Median time to response: 2.8 vs 2.8 mo | ||||
| Median DoR: 20.7 vs 13.8 mo | ||||
| Grade 3-5 TRAEs: 19.6% vs 25% | ||||
| II29 | R/R PMBCL | Pembrolizumab monotherapy | ||
| ORR of 45%, CR rate of 13% | ||||
| Median DoR not reached with median follow-up of 12.5 mo | ||||
| Grade 3-4 TRAEs: 23% | ||||
| II31 | R/R MF and SS | Pembrolizumab monotherapy | ||
| ORR of 38% | ||||
| Median DoR not reached, with median follow-up of 58 wk | ||||
| Immune-related AEs leading to treatment discontinuation in 4 patients | ||||
| Nivolumab + BV +/− ipilimumab | PD-1, CD30, CTLA-4 | I/II26 | R/R HL | Ipilimumab with BV |
| AEs: grade 3 or higher TRAEs in 43%, no grade 5 | ||||
| ORR of 76%, CR rate of 57% | ||||
| Median PFS 1.2 y, with median follow-up of 2.6 y | ||||
| I/II26 | R/R HL | Ipilimumab with nivolumab and BV | ||
| AEs: grade 3 or higher TRAEs in 50%, grade 5 in 1.5% | ||||
| ORR of 82%, CR rate of 73% | ||||
| Median PFS not reached, with median follow-up of 1.7 y |
AEs, adverse events; ALT, alanine aminotransferase; ASCT, autologous stem cell transplantation; BV, brentuximab vedotin; CR, complete response; CRS, cytokine release syndrome; CTLA-4, cytotoxic T-lymphocyte-associated protein-4; DoR, duration of response; IRR, infusion-related reaction; MF, mycosis fungoides; NHL, non-Hodgkin lymphoma; ORR, overall response rate; PFS, progression-free survival; PMBCL, primary mediastinal large B-cell lymphoma; R/R, relapsed or refractory; SS, Sézary syndrome; TRAEs, treatment-related adverse events.