Azacitidine Plus Nivolumab in Relapsed or Refractory AML
A combination of the chemotherapy drug azacitidine with the immune checkpoint inhibitor nivolumab (Opdivo) demonstrated an encouraging response rate and overall survival in patients with relapsed or refractory acute myeloid leukemia (AML), according to findings from a phase II study published by Daver et al in Cancer Discovery.
The trial was led by Naval Daver, MD, Associate Professor of Leukemia at The University of Texas MD Anderson Cancer Center. The investigators followed 70 patients with an average of 2 prior treatments (range = 1–7) for relapsed AML. Treatment consisted of intravenously or subcutaneously administered azacitidine, and nivolumab given as an infusion.
Study Findings
The researchers reported a 33% overall response, with 22% of patients treated with the combination in complete remission. The combination was particularly effective in patients who had not previously received hypomethylating agents such as azacitidine or decitabine, with an overall response rate of 52% in these patients. Six patients (9%) had stable disease for more than 6 months.
Eight patients (11%) experienced grade 3 or 4 immune-related adverse events, although the majority were successfully treated.
“In addition, bone marrow samples taken prior to treatment indicated a higher frequency of pretherapy bone marrow CD3 and CD8 cells predicted for response to therapy,” said Dr. Daver in a statement. “In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy.”
Azacitidine is approved in the United States and Europe for patients with myelodysplastic syndrome, and is approved in Europe for and commonly used in treating older patients with newly diagnosed AML. Hypomethylating agents such as azacitidine promote antitumor signaling and dampen antitumor immunity by increasing expression of the immune checkpoint antibodies programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in AML and other cancers.
Looking Ahead
A randomized phase III study with this combination in the front-line setting has been initiated.
“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,” concluded Dr. Daver.
The study was funded through a strategic collaboration with Bristol-Myers Squibb; the National Institutes of Health (CA100632 and CA016672); and the Myelodysplastic Syndromes & Acute Myeloid Leukemia Moon Shot, part of MD Anderson’s Moon Shots program.
Disclosure: See study authors’ full disclosures at cancerdiscovery.aacrjournals.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
