TargetINCA033989: mutant CALR
ActivitySpleen, anaemia, symptoms
MolecularVAF reduction; 87% / 70% CR in ET
DirectionPossible disease modification
Positive (phase 1)Watch
INCA033989
S216 (MF) · PS1983 (ET) · phase 1
- First-in-class mutant-calreticulin antibody
- MF: spleen, anaemia and symptom responses, alone and with ruxolitinib
- ET: 87% haematologic response, 70% complete; rapid and durable
- Variant allele frequency reduction; FDA Breakthrough Therapy Designation; phase 3 in ET planned
Why it matters: The first mutation-specific therapy in MPN, raising the prospect of CALR testing becoming predictive rather than only prognostic.
Split endpointNot yet
SENTRY
NCT04562389 · LBA5002 · Harrison · 353 patients
- Selinexor + ruxolitinib vs ruxolitinib in JAK-inhibitor-naive myelofibrosis
- SVR35 odds ratio 2.58 (1.60 to 4.17), P<0.0001
- Symptom score not improved over ruxolitinib alone
- Early overall survival signal from week 24; AML transformation 1.7% in both arms
- Published in the Journal of Clinical Oncology
Why it matters: A clear spleen benefit and an early survival signal, but the symptom miss complicates the regulatory picture.
PositiveWatch
SURPASS-ET
S219 · Gill · phase 3, 2-year results
- Ropeginterferon vs anagrelide in high-risk essential thrombocythaemia
- Two-year analysis of early versus delayed initiation
- Approved as Besremi for polycythaemia vera; ET under FDA review
- Decision expected 30 August 2026
Why it matters: Earlier interferon exposure gave deeper molecular and durable responses; an ET licensing decision is close.
WatchWatch
INDEPENDENCE
S215 · luspatercept · not independently verified here
- Luspatercept for anaemia in myelofibrosis on a JAK inhibitor
- Specific EHA 2026 figures were not independently verified in this fact-check
Why it matters: An anaemia-directed option in MF; treat the specifics as provisional pending the abstract.