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Momelotinib therapy for myelofibrosis: a 7-year follow-up

2018; Springer Nature; Volume: 8; Issue: 3 Linguagem: Inglês

10.1038/s41408-018-0067-6

2044-5385

Ayalew Tefferi, Daniela Barraco, Terra L. Lasho, Sahrish Shah, Kebede H. Begna, Aref Al‐Kali, William J. Hogan, Mark R. Litzow, Curtis A. Hanson, Rhett P. Ketterling, Naseema Gangat, Animesh Pardanani,

Chronic Myeloid Leukemia Treatments

Abstract One-hundred Mayo Clinic patients with high/intermediate-risk myelofibrosis (MF) received momelotinib (MMB; JAK1/2 inhibitor) between 2009 and 2010, as part of a phase 1/2 trial (NCT00935987); 73% harbored JAK2 mutations, 16% CALR , 7% MPL , 44% ASXL1 , and 18% SRSF2 . As of July 2017, MMB was discontinued in 91% of the patients, after a median treatment duration of 1.4 years. Grade 3/4 toxicity included thrombocytopenia (34%) and liver/pancreatic test abnormalities (<10%); grade 1/2 peripheral neuropathy occurred in 47%. Clinical improvement (CI) occurred in 57% of patients, including 44% anemia and 43% spleen response. CI was more likely to occur in ASXL1 -unmutated patients (66% vs 44%) and in those with <2% circulating blasts (66% vs 42%). Response was more durable in the presence of CALR type 1/like and absence of very high-risk karyotype. In multivariable analysis, absence of CALR type 1/like (HR 3.0; 95% CI 1.2–7.6) and presence of ASXL1 (HR 1.9; 95% CI 1.1–3.2) or SRSF2 (HR 2.4, 95% CI 1.3–4.5) mutations adversely affected survival. SRSF2 mutations (HR 4.7, 95% CI 1.3–16.9), very high-risk karyotype (HR 7.9, 95% CI 1.9–32.1), and circulating blasts ≥2% (HR 3.9, 95% CI 1.4–11.0) predicted leukemic transformation. Post-MMB survival (median 3.2 years) was not significantly different than that of a risk-matched MF cohort not receiving MMB.