The oral activin A receptor type I, Janus kinase 1 (JAK1), and JAK2 inhibitor momelotinib demonstrated symptom, spleen, and anemia benefits in intermediate- and high-risk myelofibrosis (MF). Post hoc analyses herein evaluated the efficacy and safety of momelotinib in patients with MF and thrombocytopenia (platelet counts <100 × 109/L) from randomized phase 3 studies: MOMENTUM (momelotinib versus danazol; JAK inhibitor experienced); SIMPLIFY-1 (momelotinib versus ruxolitinib; JAK inhibitor naïve); and SIMPLIFY-2 (momelotinib versus best available therapy; JAK inhibitor experienced); these studies were not statistically powered to assess differences in thrombocytopenic subgroups, and these analyses are descriptive. The treatment effect of momelotinib versus ruxolitinib on week 24 response rates (spleen volume reduction ≥35%/Total Symptom Score reduction ≥50%/transfusion independence) was numerically comparable or better in thrombocytopenic patients versus the overall JAK inhibitor naive population; rates were preserved with momelotinib in thrombocytopenic patients but attenuated with ruxolitinib (momelotinib: 27%/28%/67% overall versus 39%/35%/61% in thrombocytopenic group; ruxolitinib: 29%/42%/49% overall versus 0%/22%/39% in thrombocytopenic group, respectively). In contrast to ruxolitinib, momelotinib maintained high dose intensity throughout the treatment. In the JAK inhibitor experienced population, thrombocytopenic patients had the following: (1) numerically higher symptom and transfusion independence response rates with momelotinib than in control arms; and (2) preserved spleen, symptom, and transfusion independence response rates with momelotinib relative to the overall study populations. The safety profile of momelotinib in thrombocytopenic patients was also consistent with the overall study population. In summary, momelotinib represents a safe and effective treatment option for patients with MF and moderate-to-severe thrombocytopenia.

Atrium Health Wake Forest Baptist Comprehensive Cancer Center Wake Forest University School of Medicine Winston Salem NC USA

Cancer Research Institute Seoul National University College of Medicine Seoul Korea

Center for Medical Innovation Biomedical Research Institute Seoul National University Hospital Seoul Korea

Cleveland Clinic Taussig Cancer Institute Cleveland OH USA

Clinic of Hematology Cellular Therapy and Hemostaseology University of Leipzig Germany

Department of Experimental and Clinical Medicine Center of Research and Innovation of Myeloproliferative Neoplasms University of Florence Careggi University Hospital Florence Italy

Department of Hematology and Cancer Prevention Faculty of Health Sciences in Bytom Silesian Medical University Katowice Poland

Department of Hematology Faculty of Medicine University of Debrecen Hungary

Department of Hematology Szpital MSWiA w Poznaniu Poznan Poland

Department of Internal Medicine Haematology and Oncology University Hospital Brno Czech Republic

Department of Internal Medicine Seoul National University College of Medicine Seoul Korea

Department of Medicine and Department of Pathology and Immunology Division of Hematology Washington University School of Medicine St Louis MO USA

Guy's and St Thomas' NHS Foundation Trust and University College London Hospitals London United Kingdom

Guy's and St Thomas' NHS Foundation Trust London United Kingdom

Hematology Institute Tel Aviv Sourasky Medical Center Tel Aviv Israel

Princess Margaret Cancer Center University of Toronto ON Canada

Sierra Oncology a GSK company San Mateo CA USA

Teaching Hospital Mór Kaposi Kaposvár Hungary

The Sackler Faculty of Medicine Tel Aviv University Ramat Aviv Israel

The University of Texas MD Anderson Cancer Center Houston TX USA

Université de Paris AP HP Hôpital Saint Louis Centre d'Investigations Cliniques INSERM Paris France

University Hospital Brno and Central European Institute of Technology Masaryk University Brno Czech Republic

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