Phase 2 study of PD-1 blockade following autologous transplantation for patients with AML ineligible for allogeneic transplant

Allogeneic transplant remains the best post-remission therapy for non-favorable risk acute myeloid leukemia (AML) patients, due to the potent graft-versus-leukemia effect. However, some patients are ineligible due to psychosocial barriers such as lack of appropriate caregiver support, a situation more common in racial/ethnic minorities. We hypothesized that immune checkpoint inhibition following autologous transplant might represent effective post-remission therapy in such patients. We conducted a phase II study of autologous transplantation followed by pembrolizumab (8 cycles starting day +1) in such patients. The primary endpoint was 2-yr LFS. Twenty patients with non-favorable AML in CR1 or beyond were treated, median age 64 years, CR1 80%, and adverse risk AML in 40%. The majority, 55%, were non-white. Treatment was well tolerated with only 1 non-relapse death. Possible immune-related adverse events occurred in 9 patients. After a median follow-up of 80 months, 14 patients remain alive with 10 in continuous remission. Estimated 2-year LFS was 48.4% (95% CI 25.4%-68.2%), which met the trial's primary endpoint of 2-yr LFS > 25%; 2-yr OS, NRM and CIR was 68%, 5% and 46% respectively. Compared to a propensity score-matched cohort group of AML patients receiving allogeneic transplant, 3-year OS was similar (73% vs. 76% ). Study patients had inferior LFS (51% vs. 75%), but superior post-relapse survival (45% vs. 14%). In conclusion, PD1 blockade following autologous transplant is a safe and effective alternate post-remission strategy in non-favorable risk AML patients who are ineligible for allogeneic transplant, a context in which there is significant unmet need.