The effect of initial molecular profile on response to recombinant interferon-α (rIFNα) treatment in early myelofibrosis.

Background: Although recombinant interferon-α (rIFNα) effectively treats patients with early myelofibrosis, the effect of driver and high molecular risk (HMR) mutations has not been considered. In this phase 2 study, for the first time, the authors correlate response to rIFNα treatment with driver and HMR mutations.

Methods: Patients were diagnosed using World Health Organization or International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria. Only patients who had low or intermediate-1 Dynamic International Prognostic Scoring System scores with ≥15% hematopoietic bone marrow foci were included. History, symptom assessment, physical examination, and blood and bone marrow studies were performed. Genomic DNA was extracted from frozen cells, and next-generation targeted sequencing of 45 genes was performed. Either rIFNα-2b (0.5 million units subcutaneously 3 times weekly) or pegylated rIFNα-2a (45 μg weekly) with escalation was initiated. All patients were followed at the authors' institution, and regular bone marrow biopsies were encouraged. International Working Group for Myeloproliferative Neoplasms Research and Treatment and European LeukemiaNet treatment response criteria were used.

Results: Of 30 patients (16 women and 14 men; median age, 58 years), 22 were classified as low risk, and 8 were classified as intermediate-1 risk. Two patients achieved complete remission, 9 achieved partial remission, 4 had clinical improvement, 7 had stable disease; 3 had progressive disease, 1 relapsed, and 4 died. There were 22 patients with JAK mutations, 6 with CALR mutations, and 2 with MPL mutations. Seventy-three percent of patients improved or remained stable with acceptable toxicity, including 37% who achieved complete or partial remission. There was no correlation between treatment response and baseline driver mutations or Dynamic International Prognostic Scoring System scores. Of 8 poor responders, 3 had ASXL1 or SRSF2 mutations.

Conclusions: Early treatment with rIFNα in patients without HMR mutations may prevent the development of marked splenomegaly, anemia, and florid myelofibrosis. Molecular profiling at the time of diagnosis may predict prognosis and treatment response. Cancer 2017;123:2680-87. © 2017 American Cancer Society.