Multicenter, Real-World Experience Study of FLT3-Inhibitor Post-Transplant Maintenance Therapy Following Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia with FLT3-ITD

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.778-778
• Main Authors: Eissa, Yomna, Kim, Hyeoung-Joon, Moon, Joon Ho, Zeiser, Robert, Biavasco, Francesca, Lemieux, Christopher, Elemary, Mohamed, Mehra, Varun, Shah, Mili, Alotaibi, Ahmed, Cai, Yu, Song, Xianmin, Ahn, Jae-Sook, Sohn, Sang Kyun, Al Zahrani, Mohsen, Alhumaid, Muhned, Kim, Hee-Je, Kim, Dennis Dong Hwan
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-208622

Introduction Patients of acute myeloid leukemia (AML) with FLT3-internal tandem duplication (ITD) carry a considerably higher risk of relapse, even after allogeneic hematopoietic stem cell transplantation (HCT). Post-transplant maintenance (PTM) using FLT3 inhibitors (FLT3i) is known to reduce the risk of relapse and to improve long-term outcomes significantly. Although there are randomized trials analyzing the outcomes of the different FLT3i PTM, real-world experience data is still lacking. Accordingly, we performed a multicenter retrospective study to analyze the survival benefit of FLT3i PTM, its tolerability and treatment duration. This is the largest real-world experience data on FLT3i PTM to date. Patients and method We conducted a retrospective multicenter study on 440 patients from 12 centers who received an allogeneic HCT from 2007 to 2024 for AML with FLT3-ITD. The primary endpoint was relapse-free survival (RFS). The use of FLT3i PTM was treated as a time-dependent covariate. The Mantel-Byar test (MBT), which will avoid immortal bias, was conducted to compare outcomes between those who received FLT3i PTM vs those who did not. Kaplan-Meier method was used to analyze RFS, overall survival (OS) and graft-versus-host disease-free, relapse-free survival (GRFS), while cumulative incidence of competing event function was implemented for the analysis of cumulative incidence of relapse (CIR), non-relapse mortality (NRM) and chronic graft-versus-host disease (cGvHD). Multivariate analysis was conducted using either Cox's or Fine-gray model, appropriately. Results Out of 440 patients, 389 (87.7%) were in complete remission (CR) and 52 (11.8%) had relapsed/refractory disease prior to HCT. PTM with FLT3i was started in 171 (38.9%) patients either with Sorafenib (n=138, 80.7%), Gilteritinib (n=32, 18.7%) or Midostaurin (n=1). Four pts received Sorafenib PTM subsequently received Gilteritinib, while 4 pts received Gilteritinib subsequently received Sorafenib, mainly due to toxicity. The median time to start treatment with PTM was 91 days (17-685). In most of the patients, Sorafenib was mainly started either 200mg daily (n=72) or 400mg daily (n=61), while Gilteritinib was started 80 mg daily (n=14), followed by 120mg daily (n=8) and 40mg daily (n=6). Dose modification was required in 46% of pts. With a median follow-up duration of 17.5 months following PTM in all the patients who received PTM, 97 (56.7%) patients had discontinued FLT3i PTM with the most common