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Published on: September 20, 2016
Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia: A Real-World Study by the
Susana Vives1,2, David Quintela1,2, Mireia Morgades1,2
1Institut de Recerca Josep Carreras, ICO-Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain.
Background/Objectives:
Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3mut) have a dismal prognosis. FLT3mut offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials.
Methods:
We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/R FLT3mut AML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar.
Results:
The median age was 62.5 years, and 52% were women. Most patients presented with FLT3-ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4.74 months and 2.99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10.77 months vs. 4.24 months, p = 0.016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation.
Conclusions:
Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population.
Insights
Gilteritinib and quizartinib monotherapy show effectiveness and tolerability in relapsed/refractory FLT3-mutated AML patients. Real-world outcomes align with clinical trials, offering hope for this challenging patient group.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) with FLT3 mutations (FLT3mut) presents a significant therapeutic challenge with poor prognosis.
- FLT3mut represents a key target for novel therapies in AML.
- Gilteritinib and quizartinib have demonstrated efficacy as monotherapies in Phase 3 trials for FLT3mut AML.
Purpose of the Study:
- To retrospectively evaluate the real-world effectiveness and tolerability of gilteritinib and quizartinib monotherapy in R/R FLT3mut AML patients.
- To compare outcomes in a heterogeneous patient population treated prior to commercial availability.
Main Methods:
- Retrospective analysis of 50 R/R FLT3mut AML patients treated with gilteritinib or quizartinib monotherapy across 27 Spanish centers.
- Data collection included patient characteristics, treatment history, response rates (CR, CRi, PR), overall survival (OS), and toxicity profiles.
Main Results:
- The median age was 62.5 years; 80% had FLT3-ITD mutations. 56% received more than one prior line of therapy.
- Overall response rates (CR/CRi/PR) were 22%, 18%, and 16%, respectively. Median OS was 4.74 months.
- Fewer prior therapies correlated with improved OS (10.77 months vs. 4.24 months, p=0.016). Independent prognostic factors for OS included achieving CR/CRi, number of prior therapies, age, and WBC count.
- Common toxicities included febrile neutropenia, liver function abnormalities, and QT interval prolongation.
Conclusions:
- Gilteritinib and quizartinib monotherapy are effective and well-tolerated options for R/R FLT3mut AML in a real-world setting.
- Observed response and toxicity rates are comparable to Phase 3 trial findings, even in a more diverse patient cohort.
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