Encouraging clinical activity of decitabine plus ipilimumab in R/R or secondary MDS/AML

CTLA-4 blockade with ipilimumab monotherapy has modest activity in patients with a haematologic malignancy who relapsed after allogeneic haematopoietic cell transplantation (alloHCT) [1]. An ongoing phase 1 study showed that decitabine plus ipilimumab had an expected safety profile and exhibited encouraging clinical activity in patients with relapsed or refractory (R/R) or secondary myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML) [2].

This study included 2 arms based on transplantation status: with (arm A) and without (arm B) prior HCT. At data cut-off, 32 of 39 enrolled patients received ≥1 dose of decitabine plus ipilimumab (16 patients in both groups) [2]. Ms Jacqueline S. Garcia (Dana-Farber Institute, Massachusetts, USA) presented the results.

In arm A, 4 of 16 evaluable patients achieved response, including 3 with complete response (CR) and 1 with marrow CR; median overall survival was 12.8 months. The most common treatment-emergent grade 3/4 adverse events (AEs) were febrile neutropenia (n=3), aspartate aminotransferase (AST) elevation, lymphocytopenia, neutropenia, thrombocytopenia, and leukopenia (n=2 each). In total, 7 of 16 patients experienced an immune-related AE (2 responders), including 1 patient with late-onset acute graft-versus-host disease (GVHD) grade 3 (colon and liver), 4 patients with chronic GVHD, and 2 patients with grade 2/3 ipilimumab-induced colitis. All immune-related AEs were reversible with steroids, except for the grade-3 acute GVHD, which was complicated by fatal septic shock.

In arm B, objective responses were detected in 8 of 16 evaluable patients with 3 CR, 2 CR with incomplete recovery, and 3 marrow CR; median overall survival was 18.3 months. The most common treatment-emergent grade 3/4 AEs were lymphocytopenia, thrombocytopenia, leukopenia (n=5 each), neutropenia (n=4), anaemia, fatigue, lung infection, and febrile neutropenia (n=3 each). In 6 of 16 patients that had grade ≥2 immune-related AEs, all were reversible with steroids, including grade 3 colitis, grade 3 dermatitis, grade 2 pneumonitis, and grade 3 hypophysitis/grade 2 arthritis, except for a case of grade 2 dermatitis (resolved)/grade 4 immune thrombocytopenia. In this arm, no study treatment-related deaths were observed.

Taken together, immune-related AEs were frequent but mostly controllable and similar to prior observations with ipilimumab. Objective responses were observed, including in patients with history of prior treatment with hypomethylating agents. High clinical activity was observed amongst patients who did not receive alloHCT, suggesting that an alloreactive environment may not be required to benefit from CTLA-4 blockade.

1. Davids MS, et al. N Engl J Med. 2016;375:143-53.
2. Garcia JS, et al. Safety and Efficacy of Decitabine Plus Ipilimumab in Relapsed or Refractory MDS/AML in the Post-BMT or Transplant Naïve Settings. 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 170.

Posted on 18 February 202122 February 2021