C096 | Predictors of Response to Second-line Momelotinib After Ruxolitinib Failure: an Independent Cooperative Study
Year: 2025
Type: article
Abstract: 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 2nd-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 2nd-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.
Authors: F. Palandri, E.M. Elli, I. Gianesello, C. Sartor, M. Di Perna, M. Marchetti, S. Gallo, F. Itri, V. Montefusco, A. Lucchesi, E. Crisà, A. Biagi, E. Morsia, E. Beggiato, G. Benevolo, E. Abruzzese, M. Santoro, N. Pugliese, A. Iurlo, E. Calistri, M. Rossi, B. Martino, M. Tiribelli, C. Fava, A. Dizdari, M. Crugnola, F. Pane, F. Branzanti, A. Dedola, F. Heidel, A. Kuykendall, M. Breccia, G.A. Palumbo
Institutions: Istituto di Ematologia di Bologna, University of Padua, University of Bologna, Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo, Ospedale San Luigi Gonzaga, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Candiolo Cancer Institute, Marche Polytechnic University, University of Turin, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, St. Eugenio Hospital, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" di Palermo, Federico II University Hospital, University of Naples Federico II, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Istituto Oncologico Veneto, Azienda Ospedaliero-Universitaria "Renato Dulbecco", Azienda ospedaliera "Bianchi-Melacrino-Morelli", University of Udine, A. O. Ordine Mauriziano di Torino, Azienda Unità Sanitaria Locale Della Romagna, Medizinische Hochschule Hannover, Moffitt Cancer Center, Sapienza University of Rome, University of Catania
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093121850
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