The combination of Azacitidine, a standard-of-care chemotherapy drug, with Nivolumab (Opdivo), an immune checkpoint inhibitor, has demonstrated an encouraging response rate and overall survival in cases of relapsed or refractory acute myeloid leukemia (AML), making the treatment a solid alternative. Researchers are now looking to further improve the procedure by testing additional antibodies.
A Phase II study held at The University of Texas MD Anderson Cancer Center revealed that out of 70 participants, 22% managed complete remission and 33% exhibited positive responses. For patients that had not previously received hypomethylating agents (HMAs), such as Azacitidine or Decitabine, the overall response rate climbed to 52%.
“In addition, bone marrow samples taken prior to treatment indicated a higher frequency of pre-therapy bone marrow CD3 and CD8 cells predicted for response to therapy”, said study author Naval Daver, M.D. “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”.
Approved in 2004 both in the U.S. and Europe, Azacitidine has been used in treating myelodysplastic syndrome (MDS) and older patients with newly diagnosed AML. It promotes anti-tumor signaling and dampens anti-tumor immunity by increasing expression of immune checkpoint antibodies PD-1 and PD-L1 in AML and other cancers.
PD-1 and PD-L1 are proteins responsible for regulating the body’s immune system. While they protect against most threats, cancerous cells can interfere with their process and avoid destruction. Many immunotherapy drugs specifically target this interaction in order to restore balance.
The United States reports more than 60,000 new cases each year, with about one third being AML. It generally affects older patients (the average age is 68) and is uncommon before 45.