Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis.

Autor:	Gerds AT; Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH., Harrison C; Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Kiladjian JJ; Clinical Investigation Center, Hopital Saint-Louis, Paris, France., Mesa R; Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC., Vannucchi AM; Center Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Universitàdegli Studi di Firenze, Firenze, Italy., Komrokji R; Malignant Hematology Department, Moffitt Cancer Center, Tampa, FL., Bose P; Department of Leukemia, Division of Cancer Medicine, MD Anderson Cancer Center, University of Texas, Houston, TX., Kremyanskaya M; Icahn School of Medicine, Mount Sinai Hospital, New York, NY., Mead AJ; MRC Weatherall Institute of Molecular Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom., Gotlib J; Stanford Cancer Institute/Stanford University School of Medicine, Division of Hematology, Stanford, CA., Rose S; Bristol Myers Squibb, Princeton, NJ., Sanabria F; Bristol Myers Squibb, Boudry, Switzerland., Marsousi N; Bristol Myers Squibb, Boudry, Switzerland., Giuseppi AC; Bristol Myers Squibb, Princeton, NJ., Jiang H; Bristol Myers Squibb, Princeton, NJ., Palmer JM; Division of Hematology/Oncology, Mayo Clinic, Phoenix, AZ., McCaul K; Department of Medicine, Division of Hematology and Oncology, University of Tennessee Medical Center, Knoxville, TN., Ribrag V; Department of Hematology, Institut Gustave Roussy, Villejuif, France., Passamonti F; Department of Oncology and Hematology-Oncology, University of Milano Statale, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Sep 10; Vol. 8 (17), pp. 4511-4522.
DOI:	10.1182/bloodadvances.2024012939
Abstrakt:	Abstract: The ACE-536-MF-001 trial enrolled patients with myelofibrosis (n = 95) into 4 cohorts: patients in cohorts 1 and 3A were non-transfusion dependent (NTD) and had anemia; patients in cohorts 2 and 3B were transfusion dependent (TD); and patients in cohort 3A/3B had stable ruxolitinib treatment before and during the study. All patients received luspatercept (1.0-1.75 mg/kg, 21-day cycles). Treatment was extended if clinical benefit was observed at day 169. The primary end point was anemia response rate (NTD, ≥1.5 g/dL hemoglobin increase from baseline; TD, transfusion-independence) over any 12-week period during the primary treatment period (weeks 1-24). Overall, 14% of patients in cohorts 1 and 3A, 10% in cohort 2, and 26% in cohort 3B met the primary end point. In cohorts 1 and 3A (NTD), 27% and 50% of patients, respectively, had mean hemoglobin increase of ≥1.5 g/dL from baseline. Among TD patients, ∼50% had ≥50% reduction in transfusion burden. Reduction in total symptom score was observed in all cohorts, with the greatest response rate seen in cohort 3A. Overall, 94% of patients had ≥1 adverse event (AE); 47% had ≥1 treatment-related AE (TRAE; 11% grade ≥3), most frequently hypertension (18%), managed with medical intervention. One patient had a serious TRAE leading to luspatercept discontinuation. Nine patients died on treatment (unrelated to study drug). In most patients, ruxolitinib dose and spleen size remained stable. In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with previous studies. This trial was registered at www.ClinicalTrials.gov as #NCT03194542. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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