Addition of Quizartinib FLT3 Inhibitor to Cell Transplant Improves Survival in AML

Adding quizartinib, an FLT3 inhibitor, to the treatment regimen of patients with acute myeloid leukemia (AML) with FLT3 mutations (FLT3-iTD+) undergoing allogeneic hematopoietic stem cell transplant (allo-HCT) significantly improved overall survival (OS).

These data, from the phase 3 QuANTUM-First study (NCT02668653), were presented at the 2023 Society of Hematologic Oncology (SOHO) 11th Annual Meeting, held September 6-9 in Houston, Texas, by Alexander E. Perl, MD, Associate Professor of Medicine (Hematology-Oncology), University of Pennsylvania.

“FLT3 is among the most common AML genetic mutations andallo-HCT in first complete remission (CR1) improves survival. FLT3-ITD+ is associated with poor prognosis, high relapse rates, and inferior OS.Allo-HCT in CR1 improved survival, in particular in AML with high FLT3-ITD allelic frequency. Rates of relapse are still high in patients with FLT3-ITD-positive newly diagnosed AML, even after allo-HCT," Perl said during his presentation.

QuANTUM-First evaluated the efficacy and safety of quizartinib in patients with AML and FLT3-ITD up to 75 years of age and up to 3 years of continuation therapy after standard HiDAC consolidation and/or allo-HCT in CR1. Previously published data have shown that the addition of quizartinib to standard induction and consolidation chemotherapy, including allo-HCT, followed by up to around 3 years of quizartinib continuation monotherapy significantly improved OS and relapse-free survival. Perl and colleagues further investigated the impact of allo-HCT in CR1 with quizartinib treatment in this population.

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In this new analysis, the investigators found that patients that received allo-HCT plus quizartinib had a median OS of 31.9 months compared with 15.1 months in those who did not receive quizartinib (hazard ratio [HR], 0.78 [95% CI, 0.62-0.98), 2-sided P = .032). Further analyis revealed that longer survival was observed in patients treated with quizartinib versus placebo, regardless of pre allo-HCT minimal residual disease (MRD) status.

"The addition of quizartinib provided a clinically meaningful and statistically significant improvement in OS compared with standard induction and consolidation therapy alone. In patients who underwent allo-HCT in CR1, longer survival was observed in those treated with quizartinib versus placebo. Irrespective of allo-HCT performed in CR1, longer survival was observed in those treated with quizartinib versus placebo. Irrespective of pre allo-HCT MRD status, longer survival was observed in those treated with quizartinib versus placebo,” Perl said. “No new safety signals were identified in patients who underwent allo-HCT.”

REFERENCE

Schlenk RF, Montesinos P, Romero-Aguilar A, et al. Impact of allogeneic hematopoietic cell transplantation in first complete remission plus FLT3 inhibition with quizartinib in acute myeloid leukemia with FLT3-ITD: Results from QuANTUM-First. Presented at: 2023 SOHO 11th Annual Meeting; September 6–9; Houston, Texas.