Crenolanib and intensive chemotherapy in adults with newly diagnosed FLT3-mutated AML Journal Article
| Authors: | Wang, E. S.; Goldberg, A. D.; Tallman, M.; Walter, R. B.; Karanes, C.; Sandhu, K.; Vigil, C. E.; Collins, R.; Jain, V.; Stone, R. M. |
| Article Title: | Crenolanib and intensive chemotherapy in adults with newly diagnosed FLT3-mutated AML |
| Abstract: | PURPOSECrenolanib is a second-generation tyrosine kinase inhibitor with activity against FLT3-ITD- and TKD-mutant AML. We conducted a trial of crenolanib plus intensive chemotherapy in adults with newly diagnosed FLT3-mutant AML.METHODSEligible patients were 18 years and older. Induction chemotherapy consisted of cytarabine (100 mg/m2) continuous infusion on days 1-7 and anthracycline (daunorubicin 60-90 mg/mor idarubicin 12 mg/m2, once daily) on days 1-3 followed by consolidation with high-dose cytarabine (1-3 g/mtwice daily on days 1, 3, 5) and/or allogeneic transplant. Crenolanib (100 mg thrice a day) was given from day 9 until 72 hours before the next cycle, after consolidation, and for 12 months after consolidation or transplant.RESULTSForty-four patients (median age, 57; range, 19-75 years) were enrolled. Thirty-six had FLT3-ITD, and 11 had FLT3-TKD mutations. European LeukemiaNet 2017 disease risk was favorable in 34%, intermediate in 30%, and adverse in 36%. The overall response rate was 86% (complete remission [CR], 77%; CR with incomplete count recovery [CRi], 9%): 90% in patients 60 years and younger and 80% in older patients. Measurable residual disease-negative CR/CRi rates were 89% and 45%, respectively. With a 45-month follow-up, median overall survival has not been reached and the median event-free survival was 44.7 months. Among younger patients, the estimated 3-year survival was 71.4% with 15% cumulative incidence of relapse. Treatment-related serious adverse events included febrile neutropenia, diarrhea, and nausea. The median time to platelets ≥100,000/μL and absolute neutrophil count ≥1,000/μL during induction was 29 and 32 days, respectively. No new FLT3-mutant clones were detected at relapse in patients completing consolidation.CONCLUSIONCrenolanib plus intensive chemotherapy in adults with newly diagnosed FLT3-mutant AML results in high rate of deep responses and long-term survival with acceptable toxicity. A randomized trial of crenolanib versus midostaurin plus chemotherapy in younger patients is ongoing. © American Society of Clinical Oncology. |
| Keywords: | adult; clinical article; event free survival; human tissue; aged; middle aged; young adult; gene mutation; human cell; overall survival; genetics; mutation; leukemia, myeloid, acute; hydroxyurea; constipation; drug tolerability; fatigue; mortality; cancer recurrence; diarrhea; drug dose reduction; drug safety; drug withdrawal; side effect; liver dysfunction; cancer patient; cytarabine; follow up; antineoplastic agent; edema; multiple cycle treatment; nausea; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; continuous infusion; mutational analysis; carcinogenesis; abdominal pain; alanine aminotransferase blood level; backache; coughing; dizziness; febrile neutropenia; fever; rash; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; acute kidney failure; gastrointestinal toxicity; hypokalemia; maculopapular rash; minimal residual disease; daunorubicin; graft versus host reaction; patient compliance; peripheral edema; sepsis; alkaline phosphatase blood level; piperidines; headache; idarubicin; periorbital edema; leukemia relapse; melena; bilirubin blood level; benzimidazole derivative; benzimidazoles; allotransplantation; induction chemotherapy; respiratory failure; leukemia remission; clone; cumulative incidence; decreased appetite; cd135 antigen; piperidine derivative; acute myeloid leukemia; overall response rate; fms-like tyrosine kinase 3; consolidation chemotherapy; humans; human; male; female; article; absolute neutrophil count; crenolanib |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 42 |
| Issue: | 15 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2024-05-20 |
| Start Page: | 1776 |
| End Page: | 1787 |
| Language: | English |
| DOI: | 10.1200/jco.23.01061 |
| PUBMED: | 38324741 |
| PROVIDER: | scopus |
| PMCID: | PMC11107896 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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