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Retrospective Study Confirms the Palliative Role of JAK2 Inhibitors in Treatment of Myelofibrosis and Beneficial Effect of ASCT on Survival
A retrospective study proposed the value of specific pre-treatment variables in recognizing long-lived patients with myelofibrosis (MF) receiving Janus kinase 2 inhibitors (JAKis) and also validated recent findings regarding the beneficial effect on treatment response on short-term and long-term survival of allogeneic stem cell transplants (ASCT; Blood Cancer J. 2023; doi:10.1038/s41408-022-00780-9).
In this study, Naseema Gangat, MBBS, Division of Hematology, Mayo Clinic, Rochester, MN, and colleagues sought to assess long-term treatment outcomes among patients with MF using momelotinib, ruxolitinib, fedratinib, and BNS-911543. They also aimed to detect clinical and molecular predictors of response, overall and leukemia-free survival, and to investigate the influence of treatment response on survival.
A total of 183 patients were enrolled from the Mayo Clinic, including JAKi naïve patients with primary MF, post-polycythemia vera, and post essential thrombocytopenia MF registered in consecutive Phase I/II clinical trials: momelotinib [n=79], ruxolitinib [ n=50], fedratinib [n=23], and BMS -911543 [n=31] during October 2007 and July 2013. One of the trials was terminated by the sponsor in November 2015.
All the patients were followed during the year 2022. During that time period, researchers documented 177 drug discontinuations, 27 leukemic transformations, and 22 ASCT.
Results revealed that the five/ten year survival rate for all patients was 41%/16% and did not differ significantly across all four drug groups.
With regard to other results, the authors wrote, “Multivariable analysis of pre-treatment variables identified age >65 years (HR 3.5), absence of type 1/like CALR mutation (HR 2.8), baseline transfusion need (HR 2.1), and presence of ASXL1/SRSF2 mutation (HR 1.6) as risk factors for overall survival; subsequent HR-based modeling segregated three risk categories with 5/10-year survival rates of 84%/60%, 44%/14%, and 21%/5% (P < 0.01). In addition, spleen (P < 0.01) and anemia (P = 0.01) responses were independently associated with improved short-term survival while long-term survival was secured only by ASCT (5/10-year survival rate 91%/45% vs 47%/19% in non-transplanted patients; P < 0.01).”
Limitations of the study noted included its retrospective design. As a result of this limitation, the researchers could not explain the effect of successive therapies on survival rates.
“Our findings underscore the transient benefit derived from JAKi therapy in MF in terms of palliation of splenomegaly and constitutional symptoms, however, impact on long-term survival was limited and primarily determined by pre-treatment clinical and molecular risk profile,” concluded the authors, adding, “Accordingly, early ASCT referral for patients with higher risk MF is advised.”
