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| Ref Type | Journal Article | ||||||||||||
| PMID | (37379495) | ||||||||||||
| Authors | Pratz KW, Cherry M, Altman JK, Cooper BW, Podoltsev NA, Cruz JC, Lin TL, Schiller GJ, Jurcic JG, Asch A, Wu R, Hill JE, Gill SC, James AJ, Rich ES, Hasabou N, Perl AE, Levis MJ | ||||||||||||
| Title | Gilteritinib in Combination With Induction and Consolidation Chemotherapy and as Maintenance Therapy: A Phase IB Study in Patients With Newly Diagnosed AML. | ||||||||||||
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| Abstract Text | Gilteritinib 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.In 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.After 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.These 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. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | Cytarabine + Gilteritinib + Idarubicin | Phase I | Actionable | In a Phase Ib trial, the addition of Xospata (gilteritinib) to induction and consolidation chemotherapy (cytarabine plus idarubicin or daunorubicin), followed by Xospata (gilteritinib) maintenance was well tolerated and resulted in a composite complete response rate of 89% (32/36) and a median overall survival of 46.1 mo in patients with acute myeloid leukemia harboring FLT3 mutations, including FLT3-ITD and/or D835 mutations (n=25 with FLT3-ITD, 5 with D835, and 10 with both) (PMID: 37379495; NCT02236013). | 37379495 |
| FLT3 D835X | acute myeloid leukemia | predicted - sensitive | Cytarabine + Gilteritinib + Idarubicin | Phase I | Actionable | In a Phase Ib trial, the addition of Xospata (gilteritinib) to induction and consolidation chemotherapy (cytarabine plus idarubicin or daunorubicin), followed by Xospata (gilteritinib) maintenance was well tolerated and resulted in a composite complete response rate of 89% (32/36) and a median overall survival of 46.1 mo in patients with acute myeloid leukemia harboring FLT3 mutations, including FLT3-ITD and/or D835 mutations (n=25 with FLT3-ITD, 5 with D835, and 10 with both) (PMID: 37379495; NCT02236013). | 37379495 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | Cytarabine + Daunorubicin + Gilteritinib | Phase I | Actionable | In a Phase Ib trial, the addition of Xospata (gilteritinib) to induction and consolidation chemotherapy (cytarabine plus idarubicin or daunorubicin), followed by Xospata (gilteritinib) maintenance was well tolerated and resulted in a composite complete response rate of 89% (32/36) and a median overall survival of 46.1 mo in patients with acute myeloid leukemia harboring FLT3 mutations, including FLT3-ITD and/or D835 mutations (n=25 with FLT3-ITD, 5 with D835, and 10 with both) (PMID: 37379495; NCT02236013). | 37379495 |
| FLT3 D835X | acute myeloid leukemia | predicted - sensitive | Cytarabine + Daunorubicin + Gilteritinib | Phase I | Actionable | In a Phase Ib trial, the addition of Xospata (gilteritinib) to induction and consolidation chemotherapy (cytarabine plus idarubicin or daunorubicin), followed by Xospata (gilteritinib) maintenance was well tolerated and resulted in a composite complete response rate of 89% (32/36) and a median overall survival of 46.1 mo in patients with acute myeloid leukemia harboring FLT3 mutations, including FLT3-ITD and/or D835 mutations (n=25 with FLT3-ITD, 5 with D835, and 10 with both) (PMID: 37379495; NCT02236013). | 37379495 |