Predictors of anemia response to momelotinib therapy in myelofibrosis and impact on survival

We retrospectively reviewed 72 anemic patients with myelofibrosis (MF; median age 68 years), who were JAK2 inhibitor‐naïve at the time of study entry to a phase‐1/2 momelotinib clinical trial. Driver mutation profile included JAK2 69%, CALR 17%, MPL 8%, and triple‐negative 6%; other mutations includ...

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Bibliographic Details
Published in:American journal of hematology 2023-02, Vol.98 (2), p.282-289
Main Authors: Gangat, Naseema, Begna, Kebede H., Al‐Kali, Aref, Hogan, William, Litzow, Mark, Pardanani, Animesh, Tefferi, Ayalew
Format: Article
Language:English
Subjects:
Aged
Anemia
Anemia - drug therapy
Anemia - etiology
Calreticulin - genetics
Ferritin
Ferritins - genetics
Hematology
Hemoglobin
Humans
Janus kinase 2
Janus Kinase 2 - genetics
Karyotypes
Mutation
Myelofibrosis
Primary Myelofibrosis - diagnosis
Primary Myelofibrosis - drug therapy
Primary Myelofibrosis - genetics
Retrospective Studies
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Summary:We retrospectively reviewed 72 anemic patients with myelofibrosis (MF; median age 68 years), who were JAK2 inhibitor‐naïve at the time of study entry to a phase‐1/2 momelotinib clinical trial. Driver mutation profile included JAK2 69%, CALR 17%, MPL 8%, and triple‐negative 6%; other mutations included ASXL1 39% and SRSF2 17%. Momelotinib was administered at a median dose of 300 mg daily. Anemia response was assessed by formal criteria and documented in 44% of all patients with hemoglobin levels below the sex‐adjusted reference range (n = 72), 48% of those with hemoglobin  65 years, ASXL1/SRSF2 mutation, unfavorable karyotype, DIPSS‐plus high risk, red cell transfusion need and higher serum ferritin. Multivariable analysis confirmed the favorable impact of anemia response on survival (p = .02; HR 0.5, 3/5/10‐year survival; 69%/38%/25%). This survival advantage was also noted in transfusion‐dependent patients (3.7 vs. 1.9 years; p = .01; HR 0.3) and appeared to be restricted to patients with an unfavorable genetic profile. The current study suggests a short‐term survival benefit associated with anemia response in momelotinib‐treated patients with MF.
ISSN:0361-8609
1096-8652
DOI:10.1002/ajh.26778