TY - JOUR
T1 - Gilteritinib in Combination with Induction and Consolidation Chemotherapy and as Maintenance Therapy
T2 - A Phase IB Study in Patients with Newly Diagnosed AML
AU - Pratz, Keith W.
AU - Cherry, Mohamad
AU - Altman, Jessica K.
AU - Cooper, Brenda W.
AU - Podoltsev, Nikolai A.
AU - Cruz, Jose Carlos
AU - Lin, Tara L.
AU - Schiller, Gary J.
AU - Jurcic, Joseph G.
AU - Asch, Adam
AU - Wu, Ruishan
AU - Hill, Jason E.
AU - Gill, Stanley C.
AU - James, Angela J.
AU - Rich, Elizabeth Shima
AU - Hasabou, Nahla
AU - Perl, Alexander E.
AU - Levis, Mark J.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/9/10
Y1 - 2023/9/10
N2 - PURPOSEGilteritinib is a type 1 FLT3 inhibitor active as monotherapy for relapsed or refractory FLT3-mutated AML. We investigated the safety, tolerability, and efficacy of gilteritinib incorporated into intensive induction and consolidation chemotherapy, and as maintenance therapy for adult patients with newly diagnosed, non-favorable-risk AML.METHODSIn this phase IB study (2215-CL-0103; ClinicalTrials.gov identifier: NCT02236013), 103 participants were screened and 80 were allocated to treatment. The study was divided into four parts: dose escalation, dose expansion, investigation of alternate anthracycline and gilteritinib schedule, and continuous gilteritinib during consolidation.RESULTSAfter dose escalation, 120 mg gilteritinib once daily was chosen for further study. There were 58 participants evaluable for response at this dose, 36 of whom harbored FLT3 mutations. For participants with FLT3-mutated AML, the composite complete response (CRc) rate was 89% (83% were conventional complete responses), all achieved after a single induction cycle. The median overall survival time was 46.1 months. Gilteritinib was well-tolerated in this context although the median time to count recovery during induction was approximately 40 days. Longer time-to-count recovery was associated with higher trough levels of gilteritinib, which, in turn, were associated with azole use. The recommended regimen is gilteritinib at a dose of 120 mg once daily from days 4 to 17 or 8 to 21 of a 7 + 3 induction with either idarubicin or daunorubicin and from day 1 continuously with high-dose cytarabine consolidation. Maintenance therapy with gilteritinib was well-tolerated.CONCLUSIONThese results demonstrated the safety and tolerability of gilteritinib incorporated into an induction and consolidation chemotherapy regimen, and as single-agent maintenance therapy for patients with newly diagnosed FLT3-mutant AML. The data herein provide an important framework for the design of randomized trials comparing gilteritinib with other FLT3 inhibitors.
AB - PURPOSEGilteritinib is a type 1 FLT3 inhibitor active as monotherapy for relapsed or refractory FLT3-mutated AML. We investigated the safety, tolerability, and efficacy of gilteritinib incorporated into intensive induction and consolidation chemotherapy, and as maintenance therapy for adult patients with newly diagnosed, non-favorable-risk AML.METHODSIn this phase IB study (2215-CL-0103; ClinicalTrials.gov identifier: NCT02236013), 103 participants were screened and 80 were allocated to treatment. The study was divided into four parts: dose escalation, dose expansion, investigation of alternate anthracycline and gilteritinib schedule, and continuous gilteritinib during consolidation.RESULTSAfter dose escalation, 120 mg gilteritinib once daily was chosen for further study. There were 58 participants evaluable for response at this dose, 36 of whom harbored FLT3 mutations. For participants with FLT3-mutated AML, the composite complete response (CRc) rate was 89% (83% were conventional complete responses), all achieved after a single induction cycle. The median overall survival time was 46.1 months. Gilteritinib was well-tolerated in this context although the median time to count recovery during induction was approximately 40 days. Longer time-to-count recovery was associated with higher trough levels of gilteritinib, which, in turn, were associated with azole use. The recommended regimen is gilteritinib at a dose of 120 mg once daily from days 4 to 17 or 8 to 21 of a 7 + 3 induction with either idarubicin or daunorubicin and from day 1 continuously with high-dose cytarabine consolidation. Maintenance therapy with gilteritinib was well-tolerated.CONCLUSIONThese results demonstrated the safety and tolerability of gilteritinib incorporated into an induction and consolidation chemotherapy regimen, and as single-agent maintenance therapy for patients with newly diagnosed FLT3-mutant AML. The data herein provide an important framework for the design of randomized trials comparing gilteritinib with other FLT3 inhibitors.
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U2 - 10.1200/JCO.22.02721
DO - 10.1200/JCO.22.02721
M3 - Article
C2 - 37379495
AN - SCOPUS:85170111620
SN - 0732-183X
VL - 41
SP - 4236
EP - 4246
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 26
ER -
