Impact of induction approach on post-stem cell transplant (SCT) outcomes in older adults with newly diagnosed acute myeloid leukemia (AML).
Authors: Ong Faustine , Ravandi Farhad , Popat Uday R. , Kadia Tapan M. , Daver Naval Guastad , Dinardo Courtney Denton , Konopleva Marina , Borthakur Gautam , Shpall Elizabeth J. , Oran Betul , Alatrash Gheath , Mehta Rohtesh S. , Jabbour Elias , Yilmaz Musa , Issa Ghayas C. , Garcia-Manero Guillermo , Maiti Abhishek , Abbas Hussein , Champlin Richard E. , Short Nicholas James 
Published: June 2022

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Background: The optimal induction regimen for older patients (pts) with AML who are eligible for SCT is not well-established. Methods: This is a retrospective analysis of 127 pts age ≥60 years with newly diagnosed AML who underwent allogeneic SCT in first remission between 9/2012 and 7/2021 at our institution. Pts with previously treated secondary AML were excluded. Pts were divided according to induction therapy received: intensive chemotherapy (IC) (n = 44), lower-intensity therapy (LIT) without venetoclax (VEN) (n = 36), and LIT with VEN (n = 47). We compared overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) according to the induction regimen received. Results: Pts who received IC were younger than those who received LIT with or without VEN (median age: 63 vs. 68 years; P < 0.0001) and were more likely to have an ECOG performance status of 0 at time of AML diagnosis (34% vs. 14%; P = 0.02). Cytomolecular risk was well-balanced between the 3 arms; the rates of adverse cytomolecular features in the IC, LIT without VEN and LIT with VEN groups were 43%, 50%, and 55%, respectively. Donor sources and degree of HLA matching were similar in the 3 groups. Most pts (92%) in the LIT with VEN group received reduced-intensity conditioning prior to SCT, compared with 54% and 58% in the IC and LIT without VEN groups, respectively. The majority of pts achieved CR/CRi prior to SCT (IC cohort:100%, LIT without VEN: 94%, LIT with VEN: 92%); the rest had MLFS as best response. The rate of measurable residual disease (MRD) negativity by flow cytometry prior to SCT was higher in the LIT with VEN group (69%), compared with IC (58%) and LIT without VEN (49%) (P = 0.14). The median number of cycles of chemotherapy prior to SCT was 3 in all groups. The median post-SCT follow-up was 37 months. The 2-year CIR was similar in pts who received IC or LIT with VEN (18% and 19%, respectively) and was highest in pts who received LIT without VEN (36%). The 2-year NRM was lowest in pts with LIT with VEN (11%), as compared with IC or LIT without VEN (27% and 22%, respectively) (P = 0.02 for IC vs. LIT with VEN). The 1-year post-SCT RFS for pts who received IC, LIT without VEN and LIT with VEN was 58%, 50%, and 75%, respectively, and the 2-year RFS was 54%, 42% and 62%. The 1-year post-SCT OS was 63%, 58%, and 84%, respectively, and the 2-year OS was 58%, 44% and 73%. OS was statistically superior for LIT with VEN compared with LIT without VEN (P = 0.02) and there was a trend towards superior OS with LIT with VEN compared to IC (P = 0.17). Conclusions: LIT with VEN was associated with similar rates of CIR and lower NRM compared with IC. Despite the older age of pts in the LIT with VEN cohort, their post-SCT survival outcomes were noninferior, and possibly superior, to those who received IC. These results suggest that LIT with VEN is a valid induction strategy for older SCT-eligible pts with newly diagnosed AML.