Midostaurin after allogeneic stem cell transplant in patients with FLT3-internal tandem duplication-positive acute myeloid leukemia
Richard T Maziarz, Mark Levis, Mrinal M Patnaik, Bart L Scott, Sanjay R Mohan, Abhinav Deol, Scott D Rowley, Dennis D H Kim, Daniela Hernandez, Trivikram Rajkhowa, Kelly Haines, Gaetano Bonifacio, Patrice Rine, Das Purkayastha, Hugo F Fernandez, Richard T Maziarz, Mark Levis, Mrinal M Patnaik, Bart L Scott, Sanjay R Mohan, Abhinav Deol, Scott D Rowley, Dennis D H Kim, Daniela Hernandez, Trivikram Rajkhowa, Kelly Haines, Gaetano Bonifacio, Patrice Rine, Das Purkayastha, Hugo F Fernandez
Abstract
We evaluated standard-of-care (SOC) treatment with or without midostaurin to prevent relapse following allogeneic hematopoietic stem cell transplant (alloHSCT) in patients with acute myeloid leukemia (AML) harboring internal tandem duplication (ITD) in FLT3. Adults (aged 18-70 years) who received alloHSCT in first complete remission, had achieved hematologic recovery, and were transfusion independent were randomized to receive SOC with or without midostaurin (50 mg twice daily) continuously in twelve 4-week cycles. The primary endpoint was relapse-free survival (RFS) 18 months post-alloHSCT. Sixty patients were randomized (30/arm); 30 completed all 12 cycles (midostaurin + SOC, n = 16; SOC, n = 14). The estimated 18-month RFS (95% CI) was 89% (69-96%) in the midostaurin arm and 76% (54-88%) in the SOC arm (hazard ratio, 0.46 [95% CI, 0.12-1.86]; P = 0.27); estimated relapse rates were 11% and 24%, respectively. Inhibition of FLT3 phosphorylation to <70% of baseline (achieved by 50% of midostaurin-treated patients) was associated with improved RFS. The most common serious adverse events were diarrhea, nausea, and vomiting. Rates of graft-vs-host disease were similar between both arms (midostaurin + SOC, 70%; SOC, 73%). The addition of midostaurin maintenance therapy following alloHSCT may provide clinical benefit in some patients with FLT3-ITD AML. (ClinicalTrials.gov identifier: NCT01883362).
Conflict of interest statement
RTM discloses honoraria from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics; Board of Directors membership at Novartis Pharmaceuticals Corporation; consultancies with Incyte and Juno Therapeutics; and patents and royalties from Athersys, Inc; as an OHSU employee who provided and received payment for consultancy services to Novartis Pharmaceuticals Corporation, this potential conflict of interest has been reviewed and managed by OHSU. ML discloses consultancy with Novartis Pharmaceuticals Corporation, Astellas, and Daiichi Sankyo; research funding from Novartis Pharmaceuticals Corporation, Astellas, and Fujifilm; and honoraria from Novartis Pharmaceuticals Corporation. MMP discloses advisory board membership with Stemline. BLS discloses consultancy with Acceleron, Incyte, Agios, Celgene, and Alexion and research funding from Novartis Pharmaceuticals Corporation and Celgene. SRM has nothing to disclose. AD discloses consultancies with Kite Therapeutics and Novartis Pharmaceuticals Corporation. SDR has nothing to disclose. DDHK discloses consultancies with Novartis Pharmaceuticals Corporation, Bristol-Meyers Squibb, Paladin, and Pfizer and honoraria and research funding from Novartis Pharmaceuticals Corporation and Bristol-Meyers Squibb. DH and TR have nothing to disclose. KH discloses former employment with Novartis Pharmaceuticals Corporation and current employment with Regeneron Pharmaceuticals, Inc. GB and DP disclose employment with Novartis Pharmaceuticals Corporation. PR discloses former employment with Novartis Pharmaceuticals Corporation and current employment with Target CW. HFF discloses honoraria from Pfizer and Sanofi and speakers’ bureau membership with Sanofi.
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