TrialPASHA: gilteritinib vs midostaurin
PrimaryOS not met (HR 1.02)
SecondaryEFS / RFS trend favours gilteritinib
Bottom lineMidostaurin stays standard
NegativeConfirms practice
PASHA
HOVON156/AMLSG28-18 · NCT04027309 · 768 patients
- Gilteritinib vs midostaurin with intensive chemotherapy, frontline FLT3-mutated AML
- Overall survival not met: HR 1.02 (0.81 to 1.28), P=0.864
- 48-month OS 59% vs 60%
- Event-free and relapse-free survival trended in favour of gilteritinib
Why it matters: A second-generation FLT3 inhibitor did not improve survival over the first-generation standard, so midostaurin plus chemotherapy remains the frontline option.
In practiceSelected use
Menin inhibitors
Revumenib, ziftomenib
- Revumenib and ziftomenib are already approved in relapsed/refractory AML (KMT2A-rearranged or NPM1-mutant)
- Ziftomenib CR/CRh 21.4% in KOMET-001
- Frontline and combination use remains investigational
Why it matters: Menin inhibition is established in selected relapsed disease; the open question is how early in the pathway to use it.
Early phasePhase 1a
REVSTAR-123
RevSTAR-123 / AVC-201 · NCT05949125 · LBA5007 · Wermke
- Switchable allogeneic CD123 CAR-T, delivered off the shelf
- Complete remissions in CD123-positive relapsed/refractory AML
- No graft-versus-host disease and no ICANS reported
- A continuous targeting module acts as an on/off safety switch
Why it matters: An off-the-shelf, controllable CAR-T platform for a disease where conventional CAR-T has struggled with on-target toxicity.