Hypomethylating agent and venetoclax with FLT3 inhibitor “triplet” therapy in older/unfit patients with FLT3 mutated AML

• DOI: 10.1038/s41408-022-00670-0
• Publication Date: 2022-05-02T09:02:58Z
• Authors: Musa Yilmaz; Hagop Kantarjian; Nicholas J. Short; Patrick Reville; Marina Konopleva; Tapan Kadia; Courtney DiNardo; Gautam Borthakur; Naveen Pemmaraju; Abhishek Maiti; Elias Jabbour; Nitin Jain; Ghayas Issa; Koichi Takahashi; Koji Sasaki; Maro Ohanian; Sherry Pierce; Guillin Tang; Sanam Loghavi; Keyur Patel; Sa A. Wang; Guillermo Garcia-...; Michael Andreeff; Farhad Ravandi; Naval Daver
• Keywords: Venetoclax; Hypomethylating agent

Abstract In older/unfit newly diagnosed patients with FLT3 mutated acute myeloid leukemia (AML), lower intensity chemotherapy (LIC) in combination either a inhibitor or venetoclax results poor overall survival (median 8 to 12.5 months). We performed retrospective analysis of 87 AML treated on triplet (LIC + Venetoclax, [ N = 27]) and doublet inhibitor, 60]) regimens at our institution. Data were collected from prospective clinical trials 75% ( 65) 25% 22) who received the same treatment outside trial. Triplet therapy was associated significantly higher rates complete remission (CR) (67% versus 32%, P 0.002), CR/CRi (93% 70%, 0.02), FLT3-PCR negativity (96% 54%, < 0.01), flow-cytometry (83% 38%, 0.01) than doublets. At end first cycle, median time ANC > 0.5 (40 21 days, 0.15) platelet 50 K (29 25 0.6) among responders numerically longer triplets, but 60-day mortality similar (7% v 10%). With follow-up 24 months 12 for arm, 63 arm), receiving regimen had (not reached 9.5 months, 0.01). LIC combined (triplet) may be an effective frontline that should further validated prospectively.