Randomized Phase II Study to Assess the Role of Single-Agent Nivolumab to Maintain Remission in Acute Myeloid Leukemia

• Nivolumab maintenance after AML chemotherapy did not improve the PFS and OS in this randomized Phase II study.

• There were increased AEs and SAEs with nivolumab maintenance, but these AEs and SAEs were expected and manageable.

We conducted a multi-center, open-label, randomized phase II study to assess the efficacy of Nivolumab as maintenance therapy for patients with AML in first complete remission (CR) or CR with incomplete hematologic recovery (CRi) who were not candidates for SCT. Patients were stratified and randomized to Observation (Obs) or Nivolumab (Nivo, 3mg/kg IV every 2 weeks for 46 doses). The primary endpoint was progression-free survival (PFS) defined as time to disease relapse or death due to any reason. Secondary endpoints included overall survival (OS), and evaluation of adverse events following Nivolumab administration. Eighty patients were enrolled with median duration of follow-up of 24 months (33 months among survivors). PFS was 13.2 months in the Nivolumab arm (95% CI: 8.5-21.8) and 10.9 months in the Observation arm (5.4-14.9 months). Overall PFS curves were not statistically significantly different ((Nivo/Obs)= 0.92; 95% CI: 0.54, 1.56; one-sided p = 0.38). The median OS was 53.9 months in the Nivolumab arm and 30.9 months in the Observation arm. Cox regression model HR (Nivo/Obs)= 0.78; 95% CI: 0.40, 1.51; p=0.23 (one-sided). There were more adverse events (AEs) of any type (regardless of attribution) on the Nivolumab arm; 27 (71%) patients on the Nivolumab arm had a grade 3 or higher AE compared to 5 patients (12%) on the Observation arm (p<0.001). Nivolumab maintenance after AML chemotherapy failed to improve the PFS and OS in this randomized Phase II study. There were increased AEs and SAEs with nivolumab, but these AEs and SAEs were expected and manageable. ClinicalTrials.gov ID NCT02275533