Combination Therapy Shows Promise Treating Acute Myeloid Leukemia


Combination of azacitidine and nivolumab shows efficacy in patients with an average of 2 prior treatments for relapsed or refractory AML.

A combination regimen involving a standard-of-care chemotherapy and an immune checkpoint inhibitor demonstrated promising efficacy in patients with acute myeloid leukemia (AML), according to a phase 2 study.

The study, published in Cancer Discovery, evaluated the combination of azacitidine and nivolumab in 70 patients with an average of 2 prior treatments for relapsed or refractory AML.

According to the researchers, the trial was designed to assess whether the addition of nivolumab to azacitidine was safe and effective, given that single agent PD-1 antibodies have shown little effect in this patient population.

Azacitidine, the chemotherapy component of the combination, is currently approved for patients with myelodysplastic syndrome in the United States and for older patients with AML in Europe. Azacitidine is a hypomethylating agent (HMA), which promotes anti-tumor signaling and reduces anti-tumor immunity by increasing the expression of immune checkpoint antibodies PD-1 and PD-L1, according to the study.

For the trial, patients received azacitidine either intravenously or subcutaneously with nivolumab given as an infusion. According to the data, overall survival in all patients was 6.3 months, which is double the observed survival with azacitidine alone in similar patients, the researchers noted. The combination treatment also demonstrated a 33% overall response with 22% of patients in complete remission. Eleven percent of patients experienced severe or potentially life threatening adverse effects, although the majority were successfully treated, according to the study.

Additionally, the data showed that the combination was most effective in patients who had not previously received HMAs, demonstrating an overall response rate of 58% in these patients compared with 22% in HMA pre-treated patients.

The researchers also noted that bone marrow samples taken prior to treatment suggested a higher frequency of pre-therapy bone marrow CD3 and CD8 cells as potential biomarkers for response to therapy.

“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” lead author Naval Daver, MD, from University of Texas MD Anderson Cancer Center, said in a press release.

Based on these findings, a phase 3 study evaluating this combination in the frontline setting has been initiated.


Daver N, Garcia-Manero G, Basu S, et al. Efficacy, safety, and biomarkers of response to azacitidine and nivolumab in relapsed/refractory acute myeloid leukemia: a non-randomized, open-label, phase 2 study. Cancer Discovery. 2018. Doi: 10.1158/2159-8290.CD-18-0774.

Combination chemotherapy and immunotherapy effective in phase 2 leukemia study [news release]. Accessed November 9, 2018.

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