Cecelia Perkins

Predictive models for splenic response to JAK-inhibitor therapy in patients with myelofibrosis

Abstract JAK inhibitors for myelofibrosis (MF) reduce spleen size, control constitutional symptoms, and may improve survival. We studied the clinical characteristics of 548 MF patients treated with JAK inhibitors from 2008 to 2016 to better understand predictors of splenic response. Response was defined as a 50% decrease in spleen size at early (3–4 months on therapy) and late (5–12 months) timepoints after therapy initiation. Early response positively correlated with higher doses of JAK inhibitor, baseline spleen size 5–10 cm, and hemoglobin. Early response negatively correlated with baseline spleen size >20 cm and high WBC. The strongest predictor of late response was whether a patient had a response at the earlier timepoint (OR 8.88). Our response models suggest that clinical factors can be used to predict which patients are more likely to respond to JAK inhibitors, and those who do not achieve an early response, i.e. within 3–4 months, should consider alternative treatments.

Treatment With JAK Inhibitors in Myelofibrosis Patients Nullifies the Prognostic Impact of Unfavorable Cytogenetics

Micro‐Abstract In the era before Janus kinase (JAK) inhibitors, cytogenetic information was used to predict survival in myelofibrosis patients. However, the prognostic value of cytogenetics in the setting of JAK inhibitor therapy remains unknown. Our analyses suggest that initiation of JAK inhibitors nullifies the negative prognostic implication of unfavorable cytogenetics established in the pre–JAK inhibitor therapy era. Introduction In the era before Janus kinase (JAK) inhibitors, cytogenetic information was used to predict survival in myelofibrosis patients. However, the prognostic value of cytogenetics in the setting of JAK inhibitor therapy remains unknown. Patients and Methods We performed a retrospective analysis of 180 patients with bone marrow biopsy–proven myelofibrosis from 3 US academic medical centers. We fit Cox proportional hazards models for overall survival and transformation‐free survival on the bases of 3 factors: JAK inhibitor therapy as a time‐dependent covariate, dichotomized cytogenetic status (favorable vs. unfavorable), and statistical interaction between the two. The median follow‐up time was 37.1 months. Results Among patients treated with best available therapy, unfavorable cytogenetic status was associated with decreased survival (hazard ratio = 2.31; P = .025). At initiation of JAK inhibitor therapy, unfavorable cytogenetics was (nonsignificantly) associated with increased survival compared to favorable cytogenetics (hazard ratio = 0.292; P = .172). The ratio of hazard ratios was 0.126 (P = .034). These findings were similar after adjusting for standard clinical prognostic factors as well as when measured against transformation‐free survival. Conclusion The initiation of JAK inhibitor therapy appears to change the association between cytogenetics and overall survival. There was little difference in survival between treatment types in patients with favorable cytogenetics. However, the use of JAK inhibitor therapy among patients with unfavorable cytogenetics was not associated with worse survival compared to favorable cytogenetics. Our analyses suggest that initiation of JAK inhibitor therapy nullifies the negative prognostic implication of unfavorable cytogenetics established in the pre–JAK inhibitor therapy era.