Table 2 Representative clinical trials and outcomes of ICIs for treating hematologic malignancies
From: Immunotherapy in hematologic malignancies: achievements, challenges and future prospects
Drug & Target | Trial | Phase | Monotherapy/combination therapy | Type of disease | Prior lines of treatment | No. of patients | Response | Survival | FDA approval | Refs. |
|---|---|---|---|---|---|---|---|---|---|---|
Ipilimumab, CTLA-4 | NCT00060372 | I | Monotherapy | Pan-cancers, including R/R cHL | Received allo-HSCT | 29 | Only 3 patients demonstrated objective disease responses after ipilimumab alone, 1 patient achieved PR and 2 patients achieved CR | Median OS of all 29 patients was 24.7 months | Yes | |
NCT00089076 | I | Monotherapy | R/R B-NHL | 1–4 chemotherapy regimens | 18 | Only 2 patients had clinical response: 1 patient achieved PR and 1 patient achieved CR | 1 patient with FL had PR lasting 19 months and 1 patient with DLBCL had an ongoing CR ( > 31 months) | Yes | ||
NCT01896999 | I/II | Combination therapy | R/R cHL | ≥1 | 61 | ORR 76% CRR 57% | Median PFS 1.2 years | Yes | ||
Ipilimumab and Nivolumab, CTLA-4 and PD-1 | NCT01592370 | I | Combination therapy | R/R cHL, NHL, and MM | ≥1 or ≥2 | 65 | cHL: ORR 74%, CRR 23% NHL: ORR 19%, CRR 6% MM: ORR 0% | cHL: median PFS was not reached at 17 months all corhorts: median PFS was 1–2 months | Yes | |
Nivolumab, PD-1 | NCT01592370 | I | Monotherapy | R/R cHL | ≥1 without ASCT in 100 days | 23 | ORR 87% CRR 17% | PFS: 86% at 24 weeks; OS: 91% at 1 year | Yes | |
NCT03016871 | II | Comparison of monotherapy and combination therapy | R/R cHL | / | 43 | ORR 93% CRR 91% | PFS 72% at 2 years | Yes | ||
ADVL1412 | I/II | Monotherapy | Pan-cancers, including NHL and HL | ≥1 | HL 10, NHL 10 | HL: ORR 30% NHL: ORR 10% | HL: the median of cycles the patients completed was 4.5; NHL: one patient had response and remained on therapy for 11 cycles. | Yes | ||
/ | / | Monotherapy | R/R PCNSL and PTL with CNS relapse | ≥1 | 5 | ORR 100% CRR 80% | PFS: 60% at 17 months | Yes | ||
CheckMate 436 | I/II | Combination therapy | R/R PMBCL | ≥2 or received ASCT | 30 | ORR 73% CRR 37% | Median PFS and OS were not reached | Yes | ||
NCT02038933 | II | Monotherapy | R/R DLBCL | Experienced failure of ASCT | 121 | Allo-HSCT-failed: ORR 10% at 9 months, ASCT-ineligible: ORR 3% at 6 months | Allo-HSCT-failed: median PFS 1.9 months, median OS 12.2 months; allo-HSCT-ineligible: median PFS 1.4 months, OS 5.8 months | Yes | ||
NCT02329847 | I/II | Combination therapy | R/R FL/DLBCL/CLL and SLL/RT | ≥1 | 144 | CLL/SLL: ORR 61% FL: ORR 33% DLBCL: ORR 36% RT: ORR 65% | CLL/SLL: median duration of response 19.2 months FL: median PFS 9.1 months DLBCL: median PFS 2.6 months RT: median PFS 5.0 months | Yes | ||
Pembrolizumab, PD-1 | KEYNOTE-013 | I | Monotherapy | R/R cHL | Received BV without ASCT | 21 | ORR 65% CRR 16% | PFS 46% at 52 weeks | Yes | |
KEYNOTE-013 | I | Monotherapy | R/R PMBCL | Median 3 | 18 | ORR 41% | Median OS was not reached | Yes | ||
NCT02453594 | II | Monotherapy | R/R cHL | Received BV and/or HSCT | 210 | ORR 69% CRR 22.4% | PFS 72.4%, OS 99.5% at 6 months | Yes | ||
KEYNOTE-204 | III | Monotherapy | R/R cHL | ≥1 without ASCT | 151 | ORR 65.6%, CRR 24.5% | Median PFS was 13.2 months | Yes | ||
NCT02332980 | II | Monotherapy | R/R CLL, RT | ≥1 | 16 | RT: ORR 44% CLL: ORR 0% | RT cohort: median OS 10.7 months | Yes | ||
Pidilizumab (CT-011), PD-1 | NCT00532259 | II | Monotherapy | R/R DLBCL | Received ASCT | 66 | ORR 51% | PFS 72%, OS 85% at 16 months | Yes | |
NCT00904722 | II | Combination therapy | R/R FL | ≥1 | 32 | ORR 62%, CRR 52% | Median PFS was 18.8 months | Yes | ||
CT-011 Trial | I | Monotherapy | Advanced NHL, HL, CLL, MM | / | 7 | B-NHL: ORR 14%, CRR 14% | The survival time ranged from 1.7 to >77 weeks. | Yes | ||
Margrolimab, CD47 | NCT02953509 | I | Combination therapy | DLBCL, FL | ≥2 | 22 | ORR 50%, CR 36% | 91% of response were ongoing at median follow-up. | No | |
Lemzoparlimab, CD47 | NCT03934814 | I | Combination therapy | R/R NHL | ≥2 | 8 | ORR 57%, overall DCR 100% | All responders remained in clinical response at the time of data cutoff. | Yes | |
NCT04202003 | I | Monotherapy | R/R AML and MDS | ≥2 | 5 | 1 patient achieved morphologic leukemia-free state | / | – n– | ||
Evorpacept, SIRPα/CD47 | ASPEN-02 | I/II | Combination therapy | R/R MDS | ≥1 HMA-based regimen | 13 | ORR 60% of 5 ND patients, 40% of 5 R/R patients | / | Yes | |
TG-1081, CD19/CD47 | NCT03804996 | I | Comparison of monotherapy and combination therapy | R/R B-cell lymphoma | ≥1 | 14 | Monotherapy: ORR 21%; Combination with ublituximab: ORR 44%, CRR 6% | 10 patients had durable response at the time of data cutoff. | No |
