Background:While midostaurin, a pan-kinase inhibitor, represents an advance in the treatment of newly diagnosed patients Methods: Results from 29 patients in the trial (n=44) who were ≤60 years old with newly diagnosed FLT3-mutated AML are included. Patients received standard 7+3 induction with cytarabine 100 mg/m2 for 7d and either daunorubicin 90 mg/m2 (n=16) or idarubicin 12 mg/m2 (n=13) for 3d. Crenolanib 100 mg TID was administered continuously starting 24h after chemotherapy until 72h prior to the next chemo cycle. Re-induction was allowed in case of morphological evidence of residual leukemia. Consolidation cycles (up to 4) consisted of six doses of HiDAC q12h on days 1,3,5, (dosed at 3g/m2 for Results: 21 of 29 (72%) patients achieved a CR after one cycle of induction with cytarabine/anthracycline/crenolanib. An additional 3 patients achieved a CR either after re-induction (1 patient) or after treatment with HiDAC or HSCT (1 patient each). Of these 24 patients with complete remission, 18 received HiDAC consolidation (range 1-4 cycles). Sixteen underwent HSCT, including: matched unrelated (n=9), matched related (n=2) or haploidentical donor (n=2). One patient underwent a cord blood transplant. 8 patients did not receive a transplant (7 due to lack of donor, social issues or other comorbidities and 1 too early). The demographics of these 24 patients are presented in Table 1. 23/24 patients in complete remission are currently in follow up (median follow-up of 14 months, range 5-26 months). One patient died in CR due to post-transplant complications. Two patients have relapsed. Of these two, one had a bone-marrow relapse 71 days after undergoing a haplo HSCT as his only consolidation therapy. The second patient's blasts harbored four mutations (FLT3-ITD, IDH1, TET2, MLL) with a WBC count of 181,000/µL at presentation. He had a CNS relapse 7 months after a haplo HSCT following one cycle of HiDAC. The overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR) curves are shown below. Conclusion: In patients aged ≤ 60 yrs with FLT3 mutated AML, induction treatment with cytarabine/anthracycline/crenolanib resulted in a CR in 24/29 (83%) patients. With a median follow up of 14 months, only one systemic and one isolated CNS relapse have occurred in these 24 patients who achieved a CR. These data suggest that adding crenolanib, a potent FLT3 inhibitor, to standard induction chemotherapy in younger patients with FLT3-mutated AML may be associated with a low relapse rate, especially if HSCT is routinely used. A phase 3 trial of crenolanib in combination with 7+3 vs midostaurin in combination with 7+3 is being initiated. Download : Download high-res image (146KB) Download : Download full-size image Disclosures Stone: Sumitomo Dainippon: Consultancy; Roche: Consultancy; Pfizer: Consultancy; Ono: Consultancy; Novartis: Consultancy; Juno Therapeutics: Consultancy; Jazz,: Consultancy; Janssen: Consultancy; Cornerstone: Consultancy; Astellas: Consultancy; Amgen: Consultancy; Agios: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; DSMN: Consultancy. Walter: ADC Therapeutics: Research Funding; Aptevo Therapeutics: Research Funding. Jain: Arog: Equity Ownership. Collins: Arog: Research Funding; Agios: Research Funding; Celgene Corporation: Research Funding; BMS: Research Funding.
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Wang et al. (2017) studied this question.