Efficacy of Azacitidine Plus Venetoclax in Acute Myeloid Leukemia Transformed from Myelodysplastic Syndrome after Failure of Azacitidine Monotherapy.

Objective Patients with acute myeloid leukemia (AML) transformed from myelodysplastic syndrome (MDS) have a poor prognosis, including those treated with azacitidine during the MDS phase; there is no standard for the care of these patients. Recently, azacitidine plus venetoclax (AZA/VEN) was reported to prolong the survival in treatment-naïve AML patients compared with AZA monotherapy. However, the results of AZA/VEN for AML transformed from MDS, particularly after AZA monotherapy, remain unclear. The present study therefore compared the clinical results of AZA/VEN treatment in these patients. Methods Data from MDS patients diagnosed at 10 institutions in Nagasaki Prefecture were collected. Thereafter, patients with transformed AML following AZA monotherapy during the MDS phase were selected, and their treatment response and survival were analyzed. Results The overall response (OR) rate, overall survival (OS), and event-free survival (EFS) were compared among patients treated with AZA/VEN (n=13), chemotherapy (intensive and low-intensity, n=35), AZA monotherapy (mAZA, n=15), and best supportive care (BSC, n=43) after AML transformation. The corresponding OR rates were 38.5%, 20.0%, and 6.7% for the AZA/VEN, chemotherapy, and mAZA groups, respectively (p=0.235). The respective median OS and EFS were 10.7 and 8.9 months for AZA/VEN, 3.2 and 2.0 months for chemotherapy, and 3.8 and 2.7 months for mAZA, and 1.7 months for BSC (OS only) (p=0.000023 for the OS and p=0.026 for the EFS), Conclusion Our findings suggest the superiority of AZA/VEN for AML patients with transformation from MDS following AZA monotherapy.