Momelotinib in Myelofibrosis Patients With Thrombocytopenia: Post Hoc Analysis From Three Randomized Phase 3 Trials
Jean-Jacques Kiladjian,
Alessandro M. Vannucchi,
Aaron T. Gerds,
Vikas Gupta,
Srdan Verstovsek,
Miklos Egyed,
Uwe Platzbecker,
Jiří Mayer,
Sebastian Grosicki,
Árpád Illés,
Tomasz Woźny,
Stephen T. Oh,
Donal McLornan,
Ilya Kirgner,
Sung-Soo Yoon,
Claire N. Harrison,
Barbara Klencke,
Mei Huang,
Jun Kawashima,
Ruben Mesa
Affiliations
Jean-Jacques Kiladjian
1 Université de Paris, AP-HP, Hôpital Saint-Louis, Centre d’Investigations Cliniques, INSERM, Paris, France
Alessandro M. Vannucchi
2 Department of Experimental and Clinical Medicine, Center of Research and Innovation of Myeloproliferative Neoplasms (CRIMM), University of Florence, Careggi University Hospital, Florence, Italy
Aaron T. Gerds
3 Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA
Vikas Gupta
4 Princess Margaret Cancer Center, University of Toronto, ON, Canada
Srdan Verstovsek
5 The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Miklos Egyed
6 Teaching Hospital Mór Kaposi, Kaposvár, Hungary
Uwe Platzbecker
7 Clinic of Hematology, Cellular Therapy, and Hemostaseology, University of Leipzig, Germany
Jiří Mayer
8 Department of Internal Medicine, Haematology and Oncology, University Hospital Brno, Czech Republic
Sebastian Grosicki
10 Department of Hematology and Cancer Prevention, Faculty of Health Sciences in Bytom, Silesian Medical University, Katowice, Poland
Árpád Illés
11 Department of Hematology, Faculty of Medicine, University of Debrecen, Hungary
Tomasz Woźny
12 Department of Hematology, Szpital MSWiA w Poznaniu, Poznan, Poland
Stephen T. Oh
13 Department of Medicine and Department of Pathology and Immunology, Division of Hematology, Washington University School of Medicine, St. Louis, MO, USA
Donal McLornan
14 Guy’s and St Thomas’ NHS Foundation Trust and University College London Hospitals, London, United Kingdom
Ilya Kirgner
15 The Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel
Sung-Soo Yoon
17 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
Claire N. Harrison
20 Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
Barbara Klencke
21 Sierra Oncology, a GSK company, San Mateo, CA, USA
Mei Huang
21 Sierra Oncology, a GSK company, San Mateo, CA, USA
Jun Kawashima
21 Sierra Oncology, a GSK company, San Mateo, CA, USA
Ruben Mesa
22 Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA
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.
