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.

Keywords: JAK inhibitors; Myelofibrosis; myeloproliferative neoplasms; predictive models.

Figure 1.

Estimated probabilities of splenic response using the Early and Late models. To demonstrate how the early (left panel) and late (right panel) models can be used to predict splenic response, plots based on increasing spleen size are shown for a hypothetical patient treated with JAK-inhibitor therapy. Two possible WBC counts were inputted (blue circles=7*10⁹/L WBC; yellow triangles=35*10⁹/L WBC). All other patient characteristics are fixed: 70 year old male diagnosed 140 weeks ago treated at 100% of the recommended phase 2 dose, platelets 210*10⁹/L, Hgb 10.7 g/dL, requiring transfusions at baseline, and European Consensus Criteria MF-3.

Figure 2.

Estimated probabilities of splenic response for the Late-Given-Early model. This plot shows the application of the late-given-early model for predicting splenic response based on initial spleen sizes of a hypothetical patient treated with JAK-inhibitor therapy. Probabilities are stratified by no early response (left panel) or early response (right panel), with the fixed patient characteristics described in Figure 1.