Real world use of FLT3 inhibitors for treatment of FLT3+ acute myeloid leukemia (AML): A single center, propensity-score matched, retrospective cohort study
| Autor: | Anthony J. Perissinotti, Bernard L. Marini, Kristen Pettit, Dale L. Bixby, Patrick W. Burke, Lydia L. Benitez, Brian Bazzell |
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| Rok vydání: | 2021 |
| Předmět: |
Azoles
0301 basic medicine Oncology Sorafenib medicine.medical_specialty Single Center Cohort Studies 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine hemic and lymphatic diseases Induction therapy Internal medicine medicine Humans Pharmacology (medical) Midostaurin Protein Kinase Inhibitors Retrospective Studies business.industry Myeloid leukemia Retrospective cohort study Leukemia Myeloid Acute 030104 developmental biology fms-Like Tyrosine Kinase 3 chemistry 030220 oncology & carcinogenesis Mutation Flt3 mutation Propensity score matching business medicine.drug |
| Zdroj: | Journal of Oncology Pharmacy Practice. 28:1315-1325 |
| ISSN: | 1477-092X 1078-1552 |
| DOI: | 10.1177/10781552211020815 |
| Popis: | Background Patients diagnosed with acute myeloid leukemia with a FLT3 mutation (FLT3+ AML) have historically had poor outcomes. While the addition of the FLT3 inhibitors to induction therapy has been shown to improve survival outcomes in FLT3+ AML, interactions and overlapping toxicities between FLT3 inhibitors and standard of care medications used during induction therapy (e.g. azole antifungals, anthracyclines) and logistical barriers have complicated their use. To avoid these concerns, our institution has opted to defer initiation of midostaurin until after completion of induction therapy. However, to our knowledge no study confirming the effectiveness of this strategy for real world FLT3 inhibitor use has been published. Methods We performed a single center, propensity-score matched, retrospective cohort study characterizing efficacy and safety of our strategy for use of FLT3 inhibitors in the treatment of FLT3+ AML. The primary outcome was median event-free survival (EFS), while secondary endpoints included median overall survival (OS), overall response rate (ORR), 30-day mortality, duration of neutropenia, duration of thrombocytopenia, consolidation cycle delays, documented infections, and all-cause hospital readmission. Results A total of 83 FLT3+ AML patients treated with intensive induction therapy were included in the study, of whom 48 were propensity-score matched and analyzed. Baseline characteristics were similar between the patients who received a FLT3 inhibitor after induction therapy and the historical control arm. Median EFS was not significantly different but compared favorably between the FLT3 inhibitor cohort and historical controls (not reached vs 8 months, p = 0.343) with 18-month EFS of 54% and 43% for the two cohorts, respectively. Similarly, no significant differences were noted with regard to median OS (not reached vs 28.7 months, p = 0.752), ORR (79.2% vs 79.2%), or safety outcomes between groups. Conclusion Compared to historical controls, addition of a FLT3 inhibitor to intensive chemotherapy post-induction may improve EFS or OS in a real world patient cohort with longer follow-up and a larger sample size. The omission of midostaurin in induction allowed for the use of an azole antifungal and the intensification of anthracycline dose may have contributed to high remission rates in both groups. |
| Databáze: | OpenAIRE |
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