In a pilot study reported in the Journal of Clinical Oncology, Eunice S. Wang, MD, and colleagues found that the combination of crenolanib and intensive chemotherapy produced high response rates in adults with newly diagnosed FLT3-mutated acute myeloid leukemia (AML). Crenolanib is a second-generation tyrosine kinase inhibitor with activity against FLT3-ITD– and FLT3-TKD–mutated AML.
Eunice S. Wang, MD
Study Details
Forty-four patients enrolled in the U.S. multicenter study between March 2015 and December 2019 received intensive chemotherapy plus crenolanib. Induction chemotherapy consisted of cytarabine at 100 mg/m2 via continuous infusion on days 1 to 7 and daunorubicin at 60 to 90 mg/m2 or idarubicin at 12 mg/m2 once daily on days 1 to 3, followed by consolidation with high-dose cytarabine at 1 to 3 g/m2 twice daily on days 1, 3, 5 and/or allogeneic transplantation. Crenolanib was given at 100 mg three times daily from day 9 until 72 hours before the next cycle, after consolidation, and for 12 months after consolidation or transplant.
Key Findings
Complete remission/complete remission with incomplete hematologic recovery was observed in 38 (86%) of 44 patients, with complete remission seen in 34 (77%).
Among 29 patients aged ≤ 60 years, complete remission/complete remission with incomplete hematologic recovery occurred in 26 (90%), with complete remission reported in 22 (76%). Among 15 patients aged > 60 years, complete remission/complete remission with incomplete hematologic recovery occurred in 12 (80%), with all 12 having complete remission. Among evaluable patients, undetectable measurable residual disease complete remission/complete remission with incomplete hematologic recovery was observed in 16 (89%) of 18 patients aged ≤ 60 years and 5 (45%) of 11 aged > 60 years.
With a median follow-up of 45 months, median overall survival had not been reached and median event-free survival was 44.7 months in the entire population. Estimated overall survival at 1, 2, and 3 years among patients aged ≤ 65 years vs > 65 years was 78.9% vs 66.7%, 78.9% vs 46.7%, and 71.4% vs 33.3%, respectively.
The median time to platelet recovery to ≥ 100,000/mL and absolute neutrophil count recovery to ≥ 1,000/mL during induction was 29 and 32 days, respectively. No new FLT3-mutated clones were detected at relapse in patients completing consolidation.
The most common grade ≥ 3 adverse events among all patients were febrile neutropenia (in 50%) and diarrhea (in 18%). Serious adverse events occurred in 68% of patients, most commonly febrile neutropenia (in 50%). Adverse events led to death in three patients, due to sepsis in two and respiratory failure in one.
The investigators concluded, “Crenolanib plus intensive chemotherapy in adults with newly diagnosed FLT3-mutant AML results in [a] high rate of deep responses and long-term survival with acceptable toxicity. A randomized trial of crenolanib vs midostaurin plus chemotherapy in younger patients is ongoing.”
Dr. Wang, of the Leukemia Service, Roswell Park Comprehensive Cancer Center, Buffalo, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Arog Pharmaceuticals. For full disclosures of the study authors, visit ascopubs.org.
