Clinical benefit and predictors of response to momelotinib after ruxolitinib failure: A cooperative real‐world study

BACKGROUND: Momelotinib, a JAK1/JAK2/ACVR1 inhibitor, is approved for treating myelofibrosis with splenomegaly, symptoms, and moderate-to-severe anemia. Evidence on its real-world effectiveness after ruxolitinib failure is limited. METHODS: This study retrospectively analyzed 221 patients who received momelotinib after ruxolitinib failure by assessing spleen, symptom, and anemia responses, safety, and survival. Logistic regression analyses identified the responses' predictors. RESULTS: Before momelotinib initiation, all patients had received ruxolitinib for a median of 31.5 months and discontinued as a result of resistance (29.9%), intolerance (48.0%), or both (22.1%). At baseline, all patients started at full dose; 97.3% presented with cytopenia, 34.8% presented with large splenomegaly, and 43.9% were highly symptomatic. Most patients (74.7%) switched from ruxolitinib stop to momelotinib within 2 months without tapering, whereas 18.1% waited over a year. After a median exposure of 8.2 months, adverse events occurred in 35.7% of patients, which prompted dose reductions or permanent discontinuation in 12.7% and 19.9% of cases, respectively. At 6 months, 30.0% achieved ≥50% spleen length reduction (SR50), with higher responses in those with prior SR50 to ruxolitinib and shorter transition intervals. Symptom and anemia responses occurred in 39.2% and 63.4% of cases, respectively. After a median follow-up of 10.3 months, 11 patients (5.0%) progressed to blast phase, and 37 patients (16.7%) died. Two-year overall and progression-free survival (including death and blast phase transformation) were 60.9% and 59.0%, respectively. CONCLUSIONS: Momelotinib demonstrated meaningful clinical benefit and acceptable safety in cytopenic patients pretreated with ruxolitinib, which supports its role after ruxolitinib failure.

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Journal
Cancer
Published
2026-05-12
DOI
https://doi.org/10.1002/cncr.70457
Primary Topic
Myeloproliferative Neoplasms: Diagnosis and Treatment
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article
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article

Clinical benefit and predictors of response to momelotinib after ruxolitinib failure: A cooperative real‐world study

Monica Crugnola, Olga Mulas, Selene Guerzoni, Eloise Beggiato et al.
Cancer
Myeloproliferative Neoplasms: Diagnosis and Treatment
article

Clinical benefit and predictors of response to momelotinib after ruxolitinib failure: A cooperative real‐world study

Monica Crugnola, Olga Mulas, Selene Guerzoni, Eloise Beggiato, Elena Crisà, Elisabetta Calistri, F Pane, Ilaria Gianesello, Amedeo Votto, Vittorio Montefusco, Federico Itri, Alessandro Lucchesi, Giovanni Caocci, Erika Morsia, Susanna Gallo, Maria Di Perna, Marco Rossi, Filippo Branzanti, Flavia Salvatore, Alessandra Dedola, Arbana Dizdari, Elena M. Elli, F Heidel, Andrew T. Kuykendall, Annalisa Biagi, Alessandra Iurlo, Andrea Duminuco, Giulia Benevolo, Giuseppe A. Palumbo, Bruno Martino, Francesca Palandri, Alessandro Isidori, Novella Pugliese, Francesco Lanza, Chiara Sartor, Carmen Fava, Monia Marchetti, Elisabetta Abruzzese, Marco Santoro, Massimo Breccia, Sara Galimberti, Mario Tiribelli
article en

Abstract

BACKGROUND: Momelotinib, a JAK1/JAK2/ACVR1 inhibitor, is approved for treating myelofibrosis with splenomegaly, symptoms, and moderate-to-severe anemia. Evidence on its real-world effectiveness after ruxolitinib failure is limited. METHODS: This study retrospectively analyzed 221 patients who received momelotinib after ruxolitinib failure by assessing spleen, symptom, and anemia responses, safety, and survival. Logistic regression analyses identified the responses' predictors. RESULTS: Before momelotinib initiation, all patients had received ruxolitinib for a median of 31.5 months and discontinued as a result of resistance (29.9%), intolerance (48.0%), or both (22.1%). At baseline, all patients started at full dose; 97.3% presented with cytopenia, 34.8% presented with large splenomegaly, and 43.9% were highly symptomatic. Most patients (74.7%) switched from ruxolitinib stop to momelotinib within 2 months without tapering, whereas 18.1% waited over a year. After a median exposure of 8.2 months, adverse events occurred in 35.7% of patients, which prompted dose reductions or permanent discontinuation in 12.7% and 19.9% of cases, respectively. At 6 months, 30.0% achieved ≥50% spleen length reduction (SR50), with higher responses in those with prior SR50 to ruxolitinib and shorter transition intervals. Symptom and anemia responses occurred in 39.2% and 63.4% of cases, respectively. After a median follow-up of 10.3 months, 11 patients (5.0%) progressed to blast phase, and 37 patients (16.7%) died. Two-year overall and progression-free survival (including death and blast phase transformation) were 60.9% and 59.0%, respectively. CONCLUSIONS: Momelotinib demonstrated meaningful clinical benefit and acceptable safety in cytopenic patients pretreated with ruxolitinib, which supports its role after ruxolitinib failure.

CancerVol. 132(10)
University of Pisa (IT), Marche Polytechnic University (IT), University of Udine (IT), AOL (United States) (US), University of Padua (IT), University of Cagliari (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Moffitt Cancer Center (US), Medizinische Hochschule Hannover (DE), University of Catania (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Azienda ospedaliera "Bianchi-Melacrino-Morelli" (IT), Azienda Unità Sanitaria Locale Della Romagna (IT), Istituto Oncologico Veneto (IT), Azienda Ospedaliera San Gerardo (IT), CTO Andrea Alesini (IT), Federico II University Hospital (IT), Istituto di Ematologia di Bologna (IT), Azienda USL di Bologna (IT), A. O. Ordine Mauriziano di Torino (IT), Policlinico Universitario di Catania (IT), Azienda Ospedaliero-Universitaria "Renato Dulbecco" (IT), Ospedale di Parma (IT), Ospedale Santa Maria Goretti (IT), St. Eugenio Hospital (IT), Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" di Palermo (IT), Candiolo Cancer Institute (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Ospedale San Luigi Gonzaga (IT), Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo (IT), Gruppo Italiano per il Trapianto di Midollo Osseo (IT), University of Turin (IT), University of Naples Federico II (IT), Sapienza University of Rome (IT), University of Bologna (IT)
Openalex Percentile: Top 6%
Myeloproliferative Neoplasms: Diagnosis and Treatment
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