AML-609 Gilteritinib-Based Combinations Improve Survival and Enhances Allogenic Transplant Eligibility in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML): Canadian Single Center Experience

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 24; p. S325
• Main Authors: Kurup, Akhil Rajendra, Gupta, Vikas, Yee, Karen, Maze, Dawn C, Minden, Mark D, Schuh, Andre, Schimmer, Aaron D, Bankar, Aniket, Chan, Steven M, Davidson, Marta Beata, Richard-Carpentier, Guillaume, Sibai, Hassan
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2024
• Subjects: AML; FLT3; gilteritinib; relapsed-refractory; venetoclax; AML; gilteritinib; venetoclax; FLT3; relapsed-refractory
• ISSN: 2152-2650
• DOI: 10.1016/S2152-2650(24)01222-9

The prognosis for R/R FLT3-mutated AML is poor. Gilteritinib monotherapy offers modest benefits, while its combination with venetoclax shows superior response rates. Triplet combinations with azacitidine, venetoclax, and gilteritinib yield high CR/CRi rates and improved survival. Despite these findings, clinical equipoise remains regarding the optimal regimen for R/R FLT3-mutated AML patients. To evaluate the outcomes of R/R FLT3-mutated AML patients treated with gilteritinib based therapy and to compare the outcomes of gilteritinib monotherapy with gilteritinib combination therapy. Retrospective single center study. R/R FLT3-mutated AML patients treated with gilteritinib-based therapy. Over the last 5 years, 69 patients with R/R FLT3-mutated AML were treated with gilteritinib monotherapy or combination therapy. The median age was 65 years (range: 24-89). Gilteritinib monotherapy was used in 47, while 22 received combinations, including gilteritinib + venetoclax (n=8), gilteritinib + azacitidine + venetoclax (n=12) and gilteritinib + azacitidine (n=2). Forty-two patients (60.9%) had received a prior FLT3 inhibitor, predominantly midostaurin (along with intensive chemotherapy). Patients receiving gilteritinib combination therapy were a decade younger (58.5 vs 70 years; p=0.003) with less exposure to prior azacitidine-venetoclax (4.5% vs 25.4%; p=0.049). More patients in the combination arm were able to undergo allogeneic transplant (40.9% vs 12.8%; p=0.013). After a median follow-up of 34 months (95%CI: 22-35), the median EFS was 3 months (95%CI: 3-5) and median OS was 7 months (95%CI: 4-11) for the overall population. Gilteritinib combinations showed better CRc (31.8% vs 17.1%), ORR (CR + CRi/CRp/CRh + MLFS + PR) (68.2% vs 32%), median EFS (14 months [95%CI: 2-not reached] vs 3 months [95%CI: 3-5]; p=0.0363) and median OS (23 months [95%CI: 4-not reached] vs 5 months [95%CI: 3-8]; p=0.0573) compared to gilteritinib alone, respectively. On univariate analysis, age over 65, prior use of azacitidine + venetoclax, failure to achieve an ORR, and not undergoing transplant negatively impacted OS. On multivariable analysis, not undergoing transplantation, prior azacitidine + venetoclax use, and not achieving an ORR negatively impacted the OS. Patients with R/R FLT3-mutated AML treated with gilteritinib combination had better outcomes, including higher response rates, longer EFS, OS and transplant rates, making it an effective bridge to transplant.