C096 | PREDICTORS OF RESPONSE TO SECOND-LINE MOMELOTINIB AFTER RUXOLITINIB FAILURE: AN INDEPENDENT COOPERATIVE STUDY

Momelotinib (MMB), a JAK1/JAK2/ACVR1 inhibitor, is approved for the treatment of patients (pts) with myelofibrosis (MF) presenting splenomegaly, symptoms and anemia. Real-world evidence with MMB is scarce and predictors of response to 2^nd-line MMB are unknown. We conducted a sub analysis of the RUX-MF study (NCT06516406), which includes 156 MF RUXolitinib (RUX)-treated pts, receiving MMB outside clinical trials. Spleen responses to MMB were evaluated at 3 and 6 months (m) as spleen length reduction by 30% (SR30) or 50% (SR50); symptoms response required a 30% (SyR30) or a 50% (SyR50) reduction from baseline Total Symptoms Score (TSS). Mean RUX duration was 2.7 ys. The response to RUX at 6 m (RR6) score was 14% low; 43% intermediate; 43% high. Pts features at MMB start were: mean age 72.4 ys (>70 yrs, n.103); male sex 58.3%; primary MF 62.2%; Hb<10g/dL 78.9%; RBC transfusion requirement (≥1 units in the 3 m pre-MMB) 78.9%; or dependency (≥6 units, TD) 29.5%. PLT were <50 and 50-100x10⁹/L in 16.0% and 29.5% of pts. A cytopenic phenotype (Hb<10 g/dl and/or PLT<100) and a large spleen (≥10cm BCM) were present in 88.5% and 39.7% of pts, respectively. Mean TSS was 20.9 (≥20 in 48.2%). DIPSS scores were: 22.4%, int-1; 60.9%, int-2; 16.7%, high. All these variables were evaluated as predictors of SR. MMB starting dose was 200 mg/day in 98.1% of pts. Over a mean time of 7.3 m, 54 pts reported 74 adverse events, leading to MMB discontinuation in 32 (20.5%) pts. At 3 m, 35/95 (36.8%) and (27/95) 28.4% had SR30 and SR50, respectively; 45/90 (50.0%) and 22/90 (24.4%) had SyR30 and SyR50. Mean Hb levels increased from 8.8 to 9.6 g/dL; 76.6% of pts reduced their RBC transfusions rate. At 6 m, SR30 was 45.9% (28/61) and SR50 was 34.4% (21/61) of pts; SyR30 was 58.3% (35/60) and SyR50 was 33.3% (20/60). In logistic regression analysis, each increase in the RR6 category was associated with a 3-fold higher probability of noSR50 (OR:3.1, p=0.01 at 3 m; OR:3.27, p=0.02 at 6 m). Older age, cytopenic MF, large spleen, longer RUX duration, TD, and higher DIPSS were not associated with lower SR. Despite pts treated with 2^nd-line MMB had advanced, high-risk disease, nearly 30% of pts achieved SR50. RR6 score was associated with SR and may be a useful prognostic tool also in MMB-treated pts, even when the switch to MMB occurs after >6 m of RUX therapy. Cytopenias were not associated with lower SR to MMB, providing a meaningful treatment option in this difficult-to-treat population.