The Rising Era of Immune Checkpoint Inhibitors in Myelodysplastic Syndromes
Table 2
Ongoing and future monotherapy and combination phase I/II trials with immune check point inhibitors in MDS and interim results.
Trials
Authors
Treatment Arms
Estimated MDS Participants
Inclusion Criteria
Outcomes
Comments
A Phase I Trial of Ipilimumab in Patients with Myelodysplastic Syndromes after Hypomethylating Agent Failure (NCT01757639)
Zeidan et al
Ipilimumab alone
29
HMA failureor HMA refusal IPSS int-1 with excess BM blasts ≥ 5% or transfusion dependency, Int-2 or high risk;
mCR 7%; PSD 31%; OS 294 days and 400 days with maintenance
Phase 1
Stabilization of Myelodysplastic Syndromes (MDS) Following Hypomethylating Agent (HMAs) Failure Using the Immune Checkpoint Inhibitor Ipilimumab: A Phase I Trial
Zeidan et al
Ipilimumab alone
11
Primary or secondary failure of HMAs IPSS int-1 with excess BM blasts ≥ 5% or transfusion dependency, Int-2 or high risk;
SD >6 m 27.3%; SD >16 m 9%; PSD 9%; median OS 368 d; mean OS 352 d; 3 patients underwent alloSCT and remained in CR at 2,12,18 m post SCT
Showed that 3 mg/kg dose is tolerable and can lead to prolonged disease stabilization; alloSCT is feasible post ipilimumab phase 1
A Trial of Pembrolizumab (MK-3475) in Participants With Blood Cancers (MK-3475-013/KEYNOTE-013) (NCT01953692)
Garcia-Manero et al
Pembrolizumab alone
28
HMA failure IPSS int-1,int-2, or high risk
mCR 11%; PR 3%; SD 52%; HI 11%; PD 33%; median OS 23 weeks; 15% alive for >2 years
Phase 1
Nivolumab and Ipilimumab With 5-azacitidine in Patients With Myelodysplastic Syndromes (MDS) (NCT02530463)
Cohorts 1,2,3 in HMAs failure in any IPSS risk; Cohorts 4,5,6 frontline therapy in int-2/high risk MDS
Limited data available Cohort 1: No response noted; Cohort 2: ORR 30% (includes CR in 1, mCR in 2, HI in 2) in int/high-risk MDS, NR 56%, PD 12%; Cohort 4: ORR 80% (CR 6 of 17, mCR+HI in 6 of 17, HI-P in 1), PD 12%, Was too early to evaluate 2 pts
Data from cohorts 1,2,4 was presented at ASH 2016 phase 2
Lirilumab and Nivolumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (NCT02599649)
Cohort 1, 2 could have received prior non-methylating agents. No prior anti-PD-1 or PD-L1 or immune activating drugs. Prior anti-CTLA-4 is allowed as long as the last dose was >101 days ago. Phase 2
An Efficacy and Safety Study of Azacitidine Subcutaneous in Combination With Durvalumab in Previously Untreated Subjects With Higher-Risk Myelodysplastic Syndromes (NCT02775903)
NA
Randomizes participants to either azacitidine alone OR azacitidine + durvalumab
Target MDS participants: 72
Frontline treatment in IPSS-R intermediate >10% blasts or poor or very poor cytogenetics; OR IPSS-R High or very high risk
No data available yet
Enrollment began in June 2016. Phase 2
Entinostat and Pembrolizumab in Treating Patients With Myelodysplastic Syndrome After DNMTi Therapy Failure (NCT02936752)
Zeidan et al
Entinostat + Pembrolizumab
Target MDS participants: 27
DNMTi failure (no CR, PT, HI after at least 4 cycles or progression of disease) regardless of initial IPSS-R
No data available yet
Single arm open label study excludes people who received anti-PD1 or PD-L1 or HDACi or anti-CTLA-4 or other immune activating therapy within the last 3 months
A Study of Atezolizumab Administered Alone or in Combination With Azacitidine in Participants With Myelodysplastic Syndromes (NCT02508870)
R/R HMA: progression at any time on HMA OR no CR or PR or HI after HMA HMA naïve: frontline therapy in IPSS-R int, high or very high
No data available yet
Phase 1
Phase 1 Study to Evaluate MEDI4736 in Subjects With Myelodysplastic Syndrome (NCT02117219)
NA
MEDI4736 (Durvalumab) alone OR MEDI4236 + azacitidine OR MEDI4736 + tremelimumab OR MEDI4736 + azacitidine + tremelimumab
Target MDS participants: 73
R/R to HMAs or couldn’t tolerate HMAs
No data available yet
Phase 1
Study of PDR001 and/or MBG453 in Combination With Decitabine in Patients With AML or High Risk MDS (NCT03066648)
NA
Decitabine + PDR001 (spartalizumab) OR Decitabine + MBG453 OR Decitabine + MBG453 + PDR001
Target MDS participants: 70
HMA Naïve High risk MDS
No data available yet
Prior anti-PD-1/PD-L1 exposure as long as tolerated, or adverse events adequately treated with steroids >7 days of the first dose of study drug are not excluded
HMA: hypomethylating agents; R/R: relapsed/refractory; BM: bone marrow; IPSS-R: revised international prognostic scoring system; MDS: myelodysplastic syndrome; mCR: complete marrow response; PR: partial response; PD: disease progression; HI: hematologic improvement; SD: stable disease; PSD: prolonged stable disease; alloSCT: allogeneic stem cell transplant; HDACi: histone deacetylase inhibitors; NA: not available; PD-1: programmed cell death-1; PD-L1: programmed cell death ligand 1; CTLA-4: cytotoxic T cell associated protein 4; int-1: intermediate 1; int-2: intermediate 2. HMA failure: failing to achieve CR, PR, or HI after at least 4 cycles. HMA failure defined as relapse or progression after any number of cycles or no response after at least 6 HMA cycles. MBG453: T cell immunoglobulin domain and mucin domain 3 (TIM-3) blocker.
