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Multicenter Study
. 2025 Aug;59(8):703-713.
doi: 10.1177/10600280241305608. Epub 2025 Jan 12.

Evaluation of the Toxicity and Outcomes of the Combination of Midostaurin and CLAG-M in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML): A Multicenter Retrospective Analysis

Ashley Chen  1 , Grace Baek  1 , Kathryn Russell  2 , Carole Shaw  2 , Megan Othus  3 , Jonathan Cohen  1 , Shannon Palmer  4 , Jack Rasmussen  4 , Joseph Bubalo  4 , Tenzin Tsomo  5 , Tenley Schwarz  5 , Swathi Namburi  5 , Anna Halpern  2
Affiliations
Multicenter Study

Evaluation of the Toxicity and Outcomes of the Combination of Midostaurin and CLAG-M in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML): A Multicenter Retrospective Analysis

Ashley Chen et al. Ann Pharmacother. 2025 Aug.

Abstract

Background: Addition of midostaurin to standard "7+3" (cytarabine and anthracycline) significantly prolongs overall and event-free survival. At University of Washington/Fred Hutchinson Cancer Center (UW/FHCC), the standard regimen for newly diagnosed (ND) and relapsed/refractory (R/R) AML is cladribine, high-dose cytarabine, GCSF, and mitoxantrone (CLAG-M); midostaurin is added if FLT3-mutated. There is limited data on the use of FLT3-inhibitors with high-dose cytarabine regimens in AML.

Objective: This study aimed to evaluate the safety and efficacy of the combination of midostaurin with CLAG-M versus midostaurin plus 7+3 in FLT3-mutated AML patients.

Methods: This is a retrospective, multicenter review including FLT3-mutated AML patients undergoing (re)induction chemotherapy with either CLAG-M or 7+3 at UW/FHCC, Oregon Health & Science University, and Swedish Cancer Institute. The primary outcome was incidence of adverse events. Secondary outcomes included disease response per ELN2017 criteria and 28-day mortality. Excluded were patients on clinical trials or who started midostaurin 30 days after chemotherapy.

Results: Eighty patients treated from September 2016 to December 2023 were included; 36 patients received CLAG-M, and 44 patients 7+3. Baseline characteristics were similar across all institutions. Adverse event rates were similar between the 2 cohorts, except diarrhea and bleeding which were more common in the 7+3 cohort. The rate of complete remission (CR) plus CR with incomplete blood count recovery did not significantly differ between the 2 cohorts: CLAG-M, 86% versus 7+3, 70% (P = 0.11).Conclusion & relevance:The toxicity profile of CLAG-M combined with midostaurin is comparable with the combination of 7+3 with midostaurin, and induces high remissions rates in adults with FLT3-mutated AML.

Keywords: 7+3; AML; CLAG-M; FLT3.

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Conflict of interest statement

Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: GB: Honorarium for presentation from Postgraduate Healthcare Education, LLC (supported by educational grant from Bristol Myers Squibb). JB: Research funding from Angiocrine Bioscience. AC: Honorarium for presentation from Oncology Pharmacy Network. JC: Currently employed by Servier Pharmaceuticals. AH: Research funding from Jazz Pharmaceuticals, Imago Pharma, Bayer, Gilead/Forty Seven, Incyte, Karyopharm Therapeutics, Disk Medicine. Honoria for lectures/presentation from Curio sciences. Consulting with Agios, Abbive, and Notable labs. SN: Consulting or advisory role with Bristol Myers Squibb/Celgene/Juno, Janssen, Sanofi, Regeneron, ORIC Pharmaceuticals. Honoraria from Medscape. MO: Consulting or advisory role with GlycoMimetics, Cascadia Labs, Merck, Daiichi Sankyo, Biosight. Other relationships with Celgene, GlycoMimetics, Grifols.

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