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

Abstract

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.

• Authors: Animesh Pardanani, Kebede Begna, Christy Finke, Terra Lasho, Ayalew Tefferi
• Journal: American journal of hematology (Am J Hematol) Vol. 86 Issue 4 Pg. 343-5 (Apr 2011) ISSN: 1096-8652 [Electronic] United States
• PMID: 21442636 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2011 Wiley-Liss, Inc.

Chemical References

• CCL2 protein, human
• Chemokine CCL2
• Cytokines
• Interleukin-15
• Interleukin-8
• Receptors, Interleukin-2
• Thalidomide
• pomalidomide
• JAK1 protein, human
• JAK2 protein, human
• Janus Kinase 1
• Janus Kinase 2

Topics

• Adult
• Aged
• Aged, 80 and over
• Anemia (blood, etiology, genetics, prevention & control)
• Chemokine CCL2 (blood)
• Cytokines (blood)
• Female
• Humans
• Interleukin-15 (blood)
• Interleukin-8 (blood)
• Janus Kinase 1 (antagonists & inhibitors, genetics)
• Janus Kinase 2 (antagonists & inhibitors, genetics)
• Male
• Middle Aged
• Mutation
• Predictive Value of Tests
• Primary Myelofibrosis (blood, complications, drug therapy)
• Receptors, Interleukin-2 (blood)
• Thalidomide (administration & dosage, analogs & derivatives, therapeutic use)
• Treatment Outcome