Momelotinib therapy for myelofibrosis: a 7-year follow-up
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, 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
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.
Conflict of interest statement
The clinical trial was sponsored by Gilead Sciences. Inc., Foster City, CA, USA.
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Source: PubMed