Results from clinical trials of PD-1 blockade in B-cell lymphoma
| Lymphoma . | Antibody, dose . | Phase; no. of patients . | ORR (%), CR (%) . | PFS; OS; duration of response . | Rates of all AEs (%), grade 3-4 AEs (%) . | Reference . |
|---|---|---|---|---|---|---|
| PD-1 blockade in HL | ||||||
| R/R cHL | Nivolumab, 3 mg/kg every 2 wk | Phase 1; 23 | 87, 17 | PFS: 86% at 24 wk; OS: 91% at 1 y and 83% at 1.5 y; 35% of responders maintained a response for more than 1.5 y | 78, 22 | 20 |
| R/R cHL that progressed after BV | Pembrolizumab, 10 mg/kg every 2 wk | Phase 1b; 32 | 65, 16 | PFS: 46% at 52 wk; 70% of responses lasted longer than 24 wk | 97, 16 | 21 |
| R/R cHL that failed to respond to AHSCT and BV | Nivolumab, 3 mg/kg every 2 wk | Phase 2; 80 | 66.3, 9 (68, 13 according to ICML 2017 update) | At 6 mo, PFS: 76.9%; OS: 98.7%; at 12 mo, median PFS: 10.0 mo; per ICML 2017 update, with a median follow-up of 23 mo, the median duration of response was 16 mo | 99, 41 | 22 |
| R/R cHL, progressed after ASCT and/or BV | Pembrolizumab, 200 mg once every 3 wk, (median no. of treatment cycles: 13) | Phase 2; 210 | 69, 22.4 | At 6 mo, PFS: 72.4%; OS: 99.5%; 75.6% of patients had a response for ≥6 mo | Treatment-related AEs: 63% (according to ICML 2017); immune-mediated AEs: 28.6; infusion-related reactions: 6.4 | 23 |
| PD-1 blockade in B-NHL | ||||||
| R/R NHL and MM | Nivolumab, 1-3 mg/kg every 2 wk | Phase 1b; FL, 10; DLBCL, 11; other B-NHL, 10; T-NHL, 23; MM, 27 | FL, 40, 10; DLBCL, 36, 18; other B-NHL, 0, 0; T-NHL, 17, 0; MM, 4, 4* | Duration of response: 6.0-81.6 wk | All AEs: 63 (for B-NHL: 71, 26) | 107 |
| R/R PMBCL | Pembrolizumab, 10 mg/kg every 2 wk or 200 mg every 3 wk for up to 2 y | Phase 1b; 18 | 41, 11.8 | With a median follow-up of 11.3 mo, median duration of response and OS were not reached; in 2 of the 7 patients who responded, the duration of response was 20.5+ and 22.4+ months | 61, 11.8 | 109 |
| R/R CLL with RT and relapsed CLL | Pembrolizumab, 200 mg every 3 wk for up to 2 y | Phase 2; 25 (transformed DLBCL, 9; relapsed CLL, 16) | RT (transformed DLBCL), 44, 11; relapsed CLL, 0, 0 | Median OS: 10.7 mo for R/R CLL with RT after a median follow-up time of 11 mo, not reached among patients with prior ibrutinib therapy | 100, 60 | 76 |
| R/R PCNSL and PTL | Nivolumab, 3 mg/kg intravenously every 2 wk (in 1 patient with rituximab-refractory PCNSL, rituximab was continued for 3 doses after beginning treatment with nivolumab) | R/R PCNSL, 4; PTL with CNS relapse, 1 | 100, 80 | 3 patients remained free of progression at 13+ to 17+ months | 60, 20 | 110 |
| Abstracts in chronological order | ||||||
| R/R hematologic malignancies | Nivolumab, 3 mg/kg + ipilimumab, 1 mg/kg every 3 wk for 4 doses followed by nivolumab monotherapy, 3 mg/kg every 2 wk | Phase 1; HL, 31; FL, 5; DLBCL, 10; PMBCL, 1; T-NHL, 11; MM, 7 | HL, 74, 19; B-NHL, 20, 0; T-NHL, 9, 0; MM, 0, 0 | With a median follow-up of 11.4 mo, median PFS and OS in: HL: not reached; in B-NHL: PFS 1.5 mo, OS 2.9 mo; inT-NHL: PFS 2.0 mo, OS13.2 mo; in MM: PFS 2.2 mo, OS 7.6 mo | Grade ≥ 3: 29; 5 patients (8) discontinued owing to drug-related AEs | 108 |
| R/R CLL/RT | Nivolumab, 3 mg/kg + ibrutinib, 420 mg once daily | Phase 2; R/R CLL, 4; RT, 4; PR CLL after ibrutinib, 3 | R/R CLL, 75, 0; RT, 50, 25; PR CLL, 0, 0 | All immune-related AEs: R/R CLL with RT: 0; PR CLL: 33 | 111 | |
| Relapsed FL | Rituximab + pembrolizumab, 200 mg every 3 wk for up to 16 cycles | Phase 2; 30 | 80, 60 in 15 patients at the interim analysis | With a median follow-up of 7 mo, median PFS, OS, and duration of response were not reached | 37, 22 in 27 patients who had initiated therapy | 112 |
| R/R HL | Nivolumab, 3 mg/kg + BV, 1.2-1.8 mg/kg every 3 wk for 16 cycles | Phase 1; 19 | 89, 50 in 18 evaluated patients | PFS at 6 mo: 91% | Grade 3-5: ∼26 | 113 |
| R/R HL | BV + nivolumab | Phase 1/2; 62 | 85, 64 | 72, 7 | 114 | |
| R/R PMBCL | Pembrolizumab, 200 mg intravenously every 3 wk | Phase 2; 33 | 35, 13 | 58, 18 | 115 | |
| Pidilizumab trials | ||||||
| Advanced stage NHL, HL, CLL, or MM | Pidilizumab, 0.2-6 mg/kg for one cycle | Phase 1; FL, 1; DLBCL, 2; CLL, 3; HL, 1 | Only the FL patient had a CR; ORR, CR for B-NHL: 14, 14 | Responding patients: remained alive at 60 wk | All AEs: 61 | 104 |
| DLBCL after AHSCT (excluding patients with progression and active autoimmune disease) | Pidilizumab, 1.5 mg/kg every 42 d for 3 cycles 30-90 d after transplantation | Phase 2; 66 (including 4 PMBCL and 13 transformed indolent B-NHL) | ORR, 51 (35 for 35 patients who had measurable disease after AHSCT) | At 16 mo, PFS: 72%; OS: 85% | 96, 32 | 105 |
| Relapsed FL | Pidilizumab, 3 mg/kg every 4 wk for 4-12 infusions + rituximab, 375 mg/m2 17 d after the first infusion of pidilizumab | Phase 2; 32 | 66, 52 | Median PFS: 18.8 mo | 94, 0 | 106 |
| Lymphoma . | Antibody, dose . | Phase; no. of patients . | ORR (%), CR (%) . | PFS; OS; duration of response . | Rates of all AEs (%), grade 3-4 AEs (%) . | Reference . |
|---|---|---|---|---|---|---|
| PD-1 blockade in HL | ||||||
| R/R cHL | Nivolumab, 3 mg/kg every 2 wk | Phase 1; 23 | 87, 17 | PFS: 86% at 24 wk; OS: 91% at 1 y and 83% at 1.5 y; 35% of responders maintained a response for more than 1.5 y | 78, 22 | 20 |
| R/R cHL that progressed after BV | Pembrolizumab, 10 mg/kg every 2 wk | Phase 1b; 32 | 65, 16 | PFS: 46% at 52 wk; 70% of responses lasted longer than 24 wk | 97, 16 | 21 |
| R/R cHL that failed to respond to AHSCT and BV | Nivolumab, 3 mg/kg every 2 wk | Phase 2; 80 | 66.3, 9 (68, 13 according to ICML 2017 update) | At 6 mo, PFS: 76.9%; OS: 98.7%; at 12 mo, median PFS: 10.0 mo; per ICML 2017 update, with a median follow-up of 23 mo, the median duration of response was 16 mo | 99, 41 | 22 |
| R/R cHL, progressed after ASCT and/or BV | Pembrolizumab, 200 mg once every 3 wk, (median no. of treatment cycles: 13) | Phase 2; 210 | 69, 22.4 | At 6 mo, PFS: 72.4%; OS: 99.5%; 75.6% of patients had a response for ≥6 mo | Treatment-related AEs: 63% (according to ICML 2017); immune-mediated AEs: 28.6; infusion-related reactions: 6.4 | 23 |
| PD-1 blockade in B-NHL | ||||||
| R/R NHL and MM | Nivolumab, 1-3 mg/kg every 2 wk | Phase 1b; FL, 10; DLBCL, 11; other B-NHL, 10; T-NHL, 23; MM, 27 | FL, 40, 10; DLBCL, 36, 18; other B-NHL, 0, 0; T-NHL, 17, 0; MM, 4, 4* | Duration of response: 6.0-81.6 wk | All AEs: 63 (for B-NHL: 71, 26) | 107 |
| R/R PMBCL | Pembrolizumab, 10 mg/kg every 2 wk or 200 mg every 3 wk for up to 2 y | Phase 1b; 18 | 41, 11.8 | With a median follow-up of 11.3 mo, median duration of response and OS were not reached; in 2 of the 7 patients who responded, the duration of response was 20.5+ and 22.4+ months | 61, 11.8 | 109 |
| R/R CLL with RT and relapsed CLL | Pembrolizumab, 200 mg every 3 wk for up to 2 y | Phase 2; 25 (transformed DLBCL, 9; relapsed CLL, 16) | RT (transformed DLBCL), 44, 11; relapsed CLL, 0, 0 | Median OS: 10.7 mo for R/R CLL with RT after a median follow-up time of 11 mo, not reached among patients with prior ibrutinib therapy | 100, 60 | 76 |
| R/R PCNSL and PTL | Nivolumab, 3 mg/kg intravenously every 2 wk (in 1 patient with rituximab-refractory PCNSL, rituximab was continued for 3 doses after beginning treatment with nivolumab) | R/R PCNSL, 4; PTL with CNS relapse, 1 | 100, 80 | 3 patients remained free of progression at 13+ to 17+ months | 60, 20 | 110 |
| Abstracts in chronological order | ||||||
| R/R hematologic malignancies | Nivolumab, 3 mg/kg + ipilimumab, 1 mg/kg every 3 wk for 4 doses followed by nivolumab monotherapy, 3 mg/kg every 2 wk | Phase 1; HL, 31; FL, 5; DLBCL, 10; PMBCL, 1; T-NHL, 11; MM, 7 | HL, 74, 19; B-NHL, 20, 0; T-NHL, 9, 0; MM, 0, 0 | With a median follow-up of 11.4 mo, median PFS and OS in: HL: not reached; in B-NHL: PFS 1.5 mo, OS 2.9 mo; inT-NHL: PFS 2.0 mo, OS13.2 mo; in MM: PFS 2.2 mo, OS 7.6 mo | Grade ≥ 3: 29; 5 patients (8) discontinued owing to drug-related AEs | 108 |
| R/R CLL/RT | Nivolumab, 3 mg/kg + ibrutinib, 420 mg once daily | Phase 2; R/R CLL, 4; RT, 4; PR CLL after ibrutinib, 3 | R/R CLL, 75, 0; RT, 50, 25; PR CLL, 0, 0 | All immune-related AEs: R/R CLL with RT: 0; PR CLL: 33 | 111 | |
| Relapsed FL | Rituximab + pembrolizumab, 200 mg every 3 wk for up to 16 cycles | Phase 2; 30 | 80, 60 in 15 patients at the interim analysis | With a median follow-up of 7 mo, median PFS, OS, and duration of response were not reached | 37, 22 in 27 patients who had initiated therapy | 112 |
| R/R HL | Nivolumab, 3 mg/kg + BV, 1.2-1.8 mg/kg every 3 wk for 16 cycles | Phase 1; 19 | 89, 50 in 18 evaluated patients | PFS at 6 mo: 91% | Grade 3-5: ∼26 | 113 |
| R/R HL | BV + nivolumab | Phase 1/2; 62 | 85, 64 | 72, 7 | 114 | |
| R/R PMBCL | Pembrolizumab, 200 mg intravenously every 3 wk | Phase 2; 33 | 35, 13 | 58, 18 | 115 | |
| Pidilizumab trials | ||||||
| Advanced stage NHL, HL, CLL, or MM | Pidilizumab, 0.2-6 mg/kg for one cycle | Phase 1; FL, 1; DLBCL, 2; CLL, 3; HL, 1 | Only the FL patient had a CR; ORR, CR for B-NHL: 14, 14 | Responding patients: remained alive at 60 wk | All AEs: 61 | 104 |
| DLBCL after AHSCT (excluding patients with progression and active autoimmune disease) | Pidilizumab, 1.5 mg/kg every 42 d for 3 cycles 30-90 d after transplantation | Phase 2; 66 (including 4 PMBCL and 13 transformed indolent B-NHL) | ORR, 51 (35 for 35 patients who had measurable disease after AHSCT) | At 16 mo, PFS: 72%; OS: 85% | 96, 32 | 105 |
| Relapsed FL | Pidilizumab, 3 mg/kg every 4 wk for 4-12 infusions + rituximab, 375 mg/m2 17 d after the first infusion of pidilizumab | Phase 2; 32 | 66, 52 | Median PFS: 18.8 mo | 94, 0 | 106 |
Auto-HSCT, autologous hematopoietic stem cell transplantation; AE, adverse effect; CNS, central nervous system; CR, complete remission; ICML, International Conference on Malignant Lymphoma; MM, multiple myeloma; PR, partial remission.
Nivolumab therapy after radiotherapy.