Table 2.
Efficacy data of immune checkpoint inhibition in AML.
| Agent | Pathway | Study design | Trial regimen | Study population | Response state | Overall survival | Comments |
|---|---|---|---|---|---|---|---|
| Pidilizumab | PD-1 | Phase I | Single arm monotherapy | N = 8 | Minimal response in 1 AML | NR | Limited efficacy as a single agent on AML, safe and tolerable dose as 0.2–6 mg/kg for advanced hematologic malignancies. |
| Nivolumab | PD-1 | Phase II | Nivolumab+azacytidine in R/R AML | N = 70 | ORR = 33% (CR/CRi = 15, PR = 1, HI = 7) | 6.3m | Encouraging response rate and overall survival especially in salvage 1 (mOS = 10.6 months) and HMA naïve group (ORR = 52%) |
| Nivolumab | PD-1 | Nivolumab+azacytidine in frontline elderly AML | N = 10 | ORR = 60% (CR/CRp = 5, PR = 1) | NR | This trial is still enrolling | |
| Nivolumab | PD-1 | Phase II | Nivolumab, azacytidine, and ipilimumab on salvage 1–2 R/R AML | N = 14 | ORR = 43% (CR/Cri/CRp) | NR | Projected 1 year os is encouraging at 58%. This trial is still enrolling. |
| Nivolumab | PD-1 | Phase II | Nivolumab plus “3+7” standard therapy in AML | N = 42 | ORR = 77% (CR = 28, Cri = 6) | 18.5m | Addition to (I+A) induction is safe and feasible. Post-transplant severe GVHD is not significantly increased and is manageable. |
| Nivolumab | PD-1 | PhaseI/Ib | Single arm in relapsed AML after allo-SCT | N = 11 | PR in one AML patients | NR | Severe GVHD and irAEs occurred early and efficacy is modest. |
| Pembrolizumab | PD-1 | Phase II | Pembrolizumab after HiDAC in R/R AML | N = 26 | ORR = 42% (CR/CRi = 9, PR = 1, MLFS = 1) | 10.5m | Pembrolizumab is well-tolerated in this setting. Response rate is encouraging without additive toxicities after HSCT. |
| Pembrolizumab | PD-1 | PhaseI/II | Pembrolizumab followed by decitabine | N = 10 | ORR = 20% | 7 months | This first proof of principle study demonstrates the feasibility of the combination of pembrolizumab and decitabine in relapsed/refractory adult AML patients. |
| Pembrolizumab | PD-1 | Pembrolizumab for relapsed AML after allo-SCT | N = 8 | No patients showed response | NR | Treatment with pem in the post-alloSCT disease relapse setting is feasible, but can induce early and severe irAEs, for AML patients this regimen is less effective. | |
| Ipilimumab | CTLA-4 | PhaseI/Ib | Ipilimumab for R/R AML after allo-SCT | N = 12 | ORR = 42% | With median follow up of 15 months, 12 month OS was 49% | CTLA-4 blockade was a feasible approach for the treatment of patients with relapsed hematologic cancer after transplantation. Complete remissions with some durability were observed, especially in extramedullary AML. |
NR, not reported; ORR, over all response rate; OS, overall survival; CR, complete remission; CRi, complete remission with incomplete hematologic recovery; CRp, CR with incomplete platelet recovery; PR, partial response; HI, hematologic improvement; MLFS, morphological leukemia-free state; HMA, hypomethylating agents; HiDAC, high-dose cytarabine.