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Ipilimumab plus Decitabine for Patients with MDS or AML in Post-Transplant or Transplant Naïve Settings

Design and Aims

This study was a phase 1 clinical trial investigating the combination of ipilimumab (IPI), a CTLA-4 checkpoint inhibitor, and decitabine (DEC), a hypomethylating agent, for treating relapsed/refractory (R/R) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The goal was to determine whether DEC could enhance the immune response to IPI without causing excessive immune toxicity. This study provides important insights into the use of immune checkpoint inhibitors with hypomethylating agents in treating high-risk MDS/AML and highlights the need for further research on optimizing immune-based therapies in these settings.

Population Information

Post-HSCT arm: 25 patients (23 AML, 2 MDS; all relapsed/refractory).

Transplant-naïve arm: 23 patients (15 AML, 8 MDS; 20 relapsed/refractory, 3 untreated).

Data available through dbGaP

Deidentified individual participant data, Multiplex immunofluorescence staining, Olink, RNA-Seq and Whole Exome Sequencing

Principal Findings

Safety & Tolerability: The maximum tolerated dose (MTD) for IPI was determined to be 10 mg/kg, though higher doses were associated with increased immune-related adverse events (irAEs).

Efficacy: The overall response rate (ORR) was higher in transplant-naïve patients (52%) compared to post-HSCT patients (20%).

Responses were more frequent at higher IPI doses (10 mg/kg). Some patients achieved durable remission (>1 year), often linked to irAE development.

Toxicity: The most common grade ≥3 treatment-emergent adverse events included neutropenia (32%-48%), thrombocytopenia (28%-48%), and febrile neutropenia (36%-61%). irAEs were observed in 44%-48% of patients, with GVHD occurring only in the post-HSCT group.

Survival Outcomes: Median overall survival and progression-free survival did not significantly differ between the two arms. However, in transplant-naïve patients, 1-year survival was higher in those who developed irAEs (72.7%) versus those who did not (33.3%).