Combination Chemotherapy and Immunotherapy Effective
Published: 2018-11-08 |
A combination of the standard-of-care chemotherapy drug know as azacytidine, with nivolumab, an immune checkpoint inhibitor, 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 at The University of Texas MD Anderson Cancer Center.
The study followed 70 patients with an average of two prior treatments for relapsed AML, and reported a 33 percent overall response with 22 percent of patients in complete remission. The drug combination was particularly effective in patients who had not previously received hypomethylating agents (HMA's) such as azacytidine or decitabine, with an overall response rate of 52 percent in these patients.
"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 Daver. "In particular, CD3 appears 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 U.S. and Europe for patients and myelodysplastic syndrome (MDS), and is approved in Europe and commonly used in treating older patients with newly diagnosed AML. HHMAs such as azacitidine, promote anti-tumor signaling, and dampen anti-tumor immunity by increasing expression of immune checkpoint antibodies PD-1 and PD-L1 in AML and other cancers.
Treatment consisted of intravenously or subcutaneously administered azacytadine, and nivolumab given as an infusion. Eleven percent of patients experienced severe or potentially life threatening side effects, although the majority were successfully treated. Overall survival in all patients was 6.3 months. Survival in first relapsed patients was most encouraging at 10.6 months, which is double that of observed survival with azacitidine alone in similar patients at MD Anderson.