Circulating levels of MCP-1, sIL-2R, IL-15, and IL-8 predict anemia response to pomalidomide therapy in myelofibrosis

Cytokine-phenotype associations have recently been described in primary myelofibrosis and increased levels of IL-8, sIL-2R, IL-12, and IL-15 were found to be independently predictive of inferior survival. Pomalidomide therapy is effective for alleviating anemia in myelofibrosis; we examined the relationship between plasma cytokine/chemokine levels and response to treatment with pomalidomide. The study population included 32 Mayo Clinic patients (median age 66 years) who participated in two consecutive clinical trials of pomalidomide therapy for myelofibrosis-associated anemia. Ten (31%) patients achieved anemia response per International Working Group criteria. Anemia response was seen only in the presence of JAK2V617F (P = 0.04) and, in addition, predicted by lower circulating levels of MCP-1 (P = 0.003), IL-2R (P = 0.008), IL-15 (0.01), and IL-8 (P = 0.02). Marked splenomegaly and increased serum LDH level were associated with poor response (P = 0.02 and 0.03, respectively) and with each other (P = 0.02), but not with JAK2V617F. The aforementioned cytokines were not significantly associated with JAK2V617F but increased levels of sIL-2R (P = 0.01), IL-15 (P = 0.06), and MCP-1 (P = 0.07) clustered with marked splenomegaly. Current data suggest that, in the context of pomalidomide treatment, response is more likely in the presence of JAK2V617F and further predicted by the absence of marked splenomegaly or increased levels of proinflammatory cytokines.