The addition of the immunotherapy drug nivolumab to standard salvage therapy with azacitidine may benefit some patients with acute myelogenous leukemia (AML) for whom prior therapy failed. The nivolumab–azacitidine combination yielded an encouraging response rate and median overall survival duration in a preliminary analysis of an ongoing clinical trial (No. 2014-0861) at The University of Texas MD Anderson Cancer Center.
The MD Anderson group previously found that treatment resistance and poor overall survival outcomes in AML patients treated with the epigenetic agents azacitidine or decitabine may be linked to the upregulation of immune checkpoint proteins such as PD-1 (programmed cell death protein 1). Nivolumab, which inhibits PD-1, may help overcome such resistance and improve response rates and survival durations.
“The combination of azacitidine and nivolumab showed a response rate of 34%, which compares favorably to a historical response rate of 12%–15% in patients with relapsed AML treated with azacitidine alone,” said Naval Daver, M.D., an assistant professor in the Department of Leukemia. He added that the complete remission rate in the trial was 22%, and all but one of these remissions has lasted at least 7 months.
Fifty-three patients in the single-arm phase II trial of azacitidine and nivolumab were eligible for survival analysis, which showed a median overall survival of 6.0 months. A historical cohort of patients with AML who received salvage therapy with azacitidine alone had a median overall survival of 4.1 months. For patients in the trial who had received only one prior course of therapy, the median overall survival was 9.3 months, which compared favorably with historical durations of 4.5 months in similar patients.
“Longer follow-up is required to confirm the durability of the responses and the overall survival benefit,” Dr. Daver said. “It will be especially important to follow the tail of the survival curve and see if responders attain long-term survival, as this has been the major benefit of checkpoint inhibitor–based strategies in solid tumors.”
One patient in the trial died of pneumonitis/epiglottitis. Other adverse events included nephritis, skin rash, and colitis, all of which were managed with systemic steroids.
Dr. Daver and his colleagues presented their preliminary findings in December at the 58th Annual Meeting of the American Society for Hematology.
OncoLog, January 2017, Volume 62, Issue 1