Table 1.
Clinical trials studying monoclonal antibodies as immune therapy in MDS and AML.
| Study | Trial Identification | Mechanism | Study Population | Study Status | Results | MRD Status | Adverse Effects | Ref |
|---|---|---|---|---|---|---|---|---|
| Phase 1 non-randomized, open label, magrolimab and azacitidine in MDS/AML | NCT03248479 | Anti-CD47 | R/R AML or unfit treatment naïve AML or high risk MDS | Recruiting | High-risk MDS: 30/39 (91%) ORR with 42% CR, 24% marrow CR. Treatment-naïve AML: 22/34 (65%) ORR, 15 (44%) had CR. 15/21 TP53 mutants (71%) ORR, 10/21 (48%) had CR. |
High-risk MDS: 22% patients with CR or CRi or marrow CR were MRD negative Treatment-naïve AML: N/A |
Anemia, fatigue neutropenia, thrombocytopenia, infusion reaction, increased serum bilirubin, nausea | [66] |
| Phase 1 dose escalation trial, open label, single arm, magrolimab in hematologic malignancies | NCT02678338 | Anti-CD47 | R/R AML or high risk MDS | Completed | N/A | N/A | Decline in hemoglobin, increase in transfusion requirements, RBC agglutination with hemolysis. 9/19 (47%) with positive antibody screen | [69] |
| Phase 1 dose escalation trial, open label, CC-90002 in AML and high risk MDS | NCT02641002 | Anti-CD47 | R/R AML or high risk MDS | Terminated | Only 2/24 patients had stable disease, no ORR noted. No improvement in RBC transfusion requirements | N/A | Disseminated intravascular coagulation in 4 patients, diarrhea, thrombocytopenia, febrile neutropenia, anemia, increased AST/ALT, cough | [70] |
| Phase 1 dose escalation and expansion trial, open label, non randomized, TTI-621 in patients with hematologic malignancies and selected solid tumors | NCT02663518 | Binds CD47 | Relapsed or refractory hematologic malignancies, selected solid tumors | Recruiting | N/A | N/A | N/A | N/A |
| Phase 1/ 2 study, single arm, open label, ALX148 with venetoclax and azacitidine | NCT04755244 | Fusion protein that blocks CD47-SIRPalpha pathway | R/R AML or unfit treatment naïve AML | Recruiting | N/A | N/A | N/A | N/A |
| Phase 1, dose escalation trial, single arm, open label, ipilimumab or nivolumab in relapsed hematologic malignancies after allogeneic HSCT | NCT01822509 | Anti-CTLA4 monoclonal antibody | Variety of R/R hematologic malignancies | Active, not recruiting | MDS/AML specific results: CR in 4 extramedullary AML and 1 secondary AML patient out of 12 AML patients | N/A | Immune-mediated side effects in 6/28 patients (21%), causing 1 death, GVHD in 14% patients | [71] |
| Phase 2, non-randomized, open label, nivolumab and azacitidine with/without ipilimumab | NCT02397720 | Anti-PD-1 monoclonal antibody | R/R AML, unfit treatment naïve AML | Recruiting | Nivolumab and azacitidine (n = 70): ORR 33% including 22% CR/CRi, 1 PR, 7 with hematologic improvement. ORR 58% in HMA naïve, 22% in HMA pre-treated patients. Nivolumab, azacitidine and ipilimumab (n = 36%): 19% with CR/Cri, 3% with PR, 14% with durable SD. |
N/A | Grade 3 or 4 immune-mediated side effects in 11% patients Grade 3 or 4 immune-mediated toxicities in 19% patients |
[72] |
| Phase 2, single arm, open label, PD-1 inhibition (nivolumab) in AML at high risk of relapse | NCT02532231 | Anti-PD-1 monoclonal antibody | AML in remission with high risk of relapse | Recruiting | 6 month RFS 57.1%, median RFS 8.48 months | 7/9 (78%) with MRD positive stayed MRD positive and progressed. 2/9 cleared MRD. 1/6 with MRD negative status experienced recurrence | Grade 3 or 4 immune mediated toxicities were seen in 27% patients | [73] |
| Phase 1, non-randomized, open label, pembrolizumab and decitabine in newly diagnosed or R/R AML or MDS | NCT03969446 | Anti-PD-1 monoclonal antibody | R/R AML, MDS | Recruiting | N/A | N/A | N/A | N/A |
| Phase 2, randomized, azacitidine and venetoclax with or without pembrolizumab in unfit AML patients | NCT04284787 | Anti-PD-1 monoclonal antibody | Unfit patients with AML | Recruiting | N/A | N/A | N/A | N/A |
| Phase 2, randomized, intensive chemotherapy with or without pembrolizumab in fit AML patients | NCT04214249 | Anti-PD-1 monoclonal antibody | Fit patients with AML | Recruiting | N/A | N/A | N/A | N/A |
| Phase 1b, single arm, pembrolizumab for graft vs leukemia effect in acute leukemia patients with relapse post allo-HSCT | NCT03286114 | Anti-PD-1 monoclonal antibody | AML, ALL, or MDS in relapse after allo-HSCT | Recruiting | N/A | N/A | N/A | N/A |
| Phase 1b study, single arm, open label, pembrolizumab and entinostat in MDS after HMA failure | NCT02936752 | Anti-PD-1 monoclonal antibody | MDS regardless of risk category or oligoblastic AML after HMA failure | Active, not recruiting | N/A | N/A | N/A | N/A |
| Phase 1, non-randomized, sabatolimab with HMAs in AML and high risk MDS | NCT03066648 | Anti-TIM-3 monoclonal antibody | AML and high risk MDS | Active, not recruiting | AML (n = 34): ORR 41.2%, 12 month PFS was 44% High-risk MDS (n = 35): ORR 62.9%, 12 month PFS 58.1% |
N/A | Thrombocytopenia, neutropenia, anemia, pneumonia, 7 immune mediate adverse events | [74] |
Abbreviations: R/R, relapsed/refractory; ORR, objective response rate; CR, complete response; CRi, incomplete count recovery; MRD, minimal residual disease; HSCT, hematopoietic stem cell transplantation; ALL, acute lymphoblastic leukemia; HMA, hypomethylating agent; PFS, progression-free survival.