Hematology · 1 h ago
Phase 2 trial finds no overall remission benefit from adding midostaurin to venetoclax and cytarabine in older AML
In the randomized phase 2 INTERVENE study, 120 patients aged 60 years or older with newly diagnosed AML received low-dose cytarabine and venetoclax, with or without sequential midostaurin. The combination did not improve remission rates overall, but a small FLT3-ITD subgroup showed signals of benefit that require confirmation.
- Overall CRc was 72% versus 68%.
- FLT3-ITD subgroup included 29 patients.
- Subgroup survival and molecular-clearance results favored midostaurin.
- Phase 2 findings need confirmation.
INTERVENE (ACTRN12619001655134) evaluated whether adding midostaurin to low-dose cytarabine and venetoclax could improve outcomes in newly diagnosed AML in patients aged 60 years or older with non-adverse karyotype. After an 18-patient run-in established tolerability, 120 patients were randomized 2:1 to the three-drug regimen or low-dose cytarabine plus venetoclax. Midostaurin was given sequentially, on days 11-28; the primary endpoint was composite complete remission (CRc).
CRc was 72% with midostaurin and 68% without it, showing no overall improvement. Among the 29 patients with FLT3-ITD, CRc was 82% versus 57%. FLT3-ITD clearance by ultrasensitive next-generation sequencing was 65% versus 0%, and median overall survival was 24.2 versus 8.8 months (hazard ratio 0.34; 95% credible interval 0.071-0.960).
The findings suggest a possible benefit in FLT3-ITD AML, but the subgroup was small and the study was phase 2. The reported subgroup estimates are uncertain; these results do not establish a practice-changing benefit for the overall study population.
In practice
For older adults with newly diagnosed AML who are not receiving intensive chemotherapy, this randomized phase 2 study did not show an overall remission advantage from adding sequential midostaurin to low-dose cytarabine and venetoclax. Results in the 29-patient FLT3-ITD subgroup—including higher remission, more molecular clearance and longer median survival—are promising but uncertain. The small subgroup and phase 2 design mean these findings do not establish a treatment change; confirmation is needed before inferring benefit for this population.
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Blood: A randomized phase 2 study combining midostaurin, low-dose cytarabine and venetoclax in newly diagnosed AML ≥60 years ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.