Abstract

Background

Patients with relapsed or refractory acute myeloid leukemia (R/R AML) with FLT3 internal tandem duplication (FLT3-ITD) have an infrequent response to salvage chemotherapy. We aimed to investigate the activity of sorafenib plus triplet therapy with venetoclax, azacitidine, and homoharringtonine (VAH) as salvage therapy for this population.

Methods and findings

This multicentre, single-arm, phase 2 study was done at twelve hospitals in China, to investigate the activity and safety of sorafenib plus VAH. Eligible patients were R/R AML with FLT3-ITD (aged 18-65 years) with an Eastern Cooperative Oncology Group performance status of 0-2. Patients received venetoclax (100mg on day 1, 200mg on day 2, and 400mg on days 3-14) and azacitidine (75 mg/m² on days 1-7) and homoharringtonine (1 mg/m² on days 1-7). Sorafenib (400 mg twice daily) was given on 1-14 during each course and continuously during maintenance.The primary endpoint was composite complete remission (CRc) after 2 cycles. Secondary outcomes included overall response rate (ORR), safety and survival.Between July 9, 2020, and March 19, 2022, 58 patients were assessed for eligibility, 51 of whom enrolled. Median age was 47 years (IQR 31-57). CRc was 76.5% with ORR of 82.4%. At a median follow-up of 10.3 months (IQR, 6.6-16.5), median duration of CRc was not reached (NR) overall survival was 18.1 months (95% CI, 12.2-NR) and event-free survival was 13.2 months (95% CI, 7.3-NR). The grade 3 or 4 adverse events occurring in ≥10% of patients included neutropenia in 47 (92·2%), thrombocytopenia in 41 (80.4%), anemia in 35 (68.6%), febrile neutropenia in 29 (56.9%), pneumonia in 13 (25.5%) and sepsis in 6 (11.8%) patients. Treatment-related death occurred in 2 (3.9%) patients.

Conclusions

Sorafenib plus VAH regimen is well tolerated and highly active for R/R AML with FLT3-ITD. This regimen might be a suitable therapeutic option for this population, and larger population trials are needed to be explored.

No relevant conflicts of interest to declare.

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2023
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