Ropeginterferon alfa-2b for pre-fibrotic primary myelofibrosis and DIPSS low/intermediate-risk myelofibrosis.

6573 Background: There is currently no consensus on the optimal treatment for primary myelofibrosis (PMF) in pre-/early fibrotic stage (pre-PMF) and DIPPS low/intermediate-1 risk MF. Ropeginterferon alfa 2b (Ropeg-IFN-α2b) is a next-generation monopegylated interferon alfa-2b developed specifically to treat myeloproliferative neoplasms (MPN). Methods: Key eligibility included morphologically confirmed pre-PMF, and DIPSS low/intermediate-1 risk overt PMF, post-polycythemia vera MF (PPV-MF), and post-essential thrombocythemia MF (PET-MF) in patients requiring cytoreduction. The primary end-points were responses in hemoglobin (from 10 g/dL to upper reference range), white blood cell (to < 10 x 10 9 /L) and platelet (to ≤ 400 x 10 9 /L) at 24 and 52 weeks. Secondary endpoints included safety (adverse events, AEs), reductions in variant allele frequencies (VAF) of driver and non-driver genes, spleen length by palpation, Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF-TSS), and bone marrow fibrosis. Patients received Ropeg-IFN-α2b at a dose of 250 mcg at Week 0, followed by 350 mcg at Week 2 and 500 mcg every 2 weeks from Week 4 onwards. Results: At the data cut-off of 30 June 2024, 71 patients (40 men and 31 women) with a median age of 60 (range: 31-86) years were enrolled. At a median follow up of 119 (10-131) weeks, responses in hemoglobin, white blood cell and platelet counts were 73.9%, 82.6% and 100% at Week 24; and 76.2%, 79.4% and 100% at Week 52, respectively. Reduction in JAK2 V617F VAF was found in 16 of 47 evaluable patients (34%) at Week 24, and 20 of 41 evaluable patients (44%) at Week 52. Reduction in CALR VAF was found in 10 of 19 evaluable patients (53%) at Week 24, and 6 of 14 evaluable patients (43%) at Week 52. Reduction of spleen size was found in 9 of 19 patients (47%) at Week 24, and 9 of 17 patients (53%) at Week 52. Reduction in MPNSAF-TSS of ≥50% was found in 27 of 63 evaluable patients (42.9%) at Week 24, and 23 of 57 patients (42.1%) at Week 52. The most common non-hematologic AEs included transaminitis (grade 1-2, N=35, 49.2%); malaise (grade 1-2, N=29, 40.8%; grade 3-4, N=1, 1.4%), and hair loss (grade 1-2, N=24, 33.8%). The most common hematologic AEs were anemia (grade 1-2, N=15, 21.1%; grade 3-4, N=6, 8.5%), neutropenia (grade 1-2, N=15, 21.1%; grade 3-4, N=4, 5.6%) and thrombocytopenia (grade 1-2, N=8, 11.2%; grade 3-4, N=3, 4.2%). Thrombohemorrhagic events or progression to blast-phase MF was not observed during the study. Conclusions: Ropeg-IFN-α2b was well-tolerated and induced clinical, hematologic and molecular responses in patients with pre-PMF and low/intermediate-1-risk MF. Clinical trial information: NCT04988815 .