Myelofibrosis, a Philadelphia-negative myeloproliferative
neoplasm, is in a new treatment era after the discovery of the JAK2V617F mutation in 2005.
JAK inhibitors boast improvements in disease-related symptoms,
splenomegaly, and overall survival; however, treatment of
myelofibrosis remains a challenge, given the lack of improvement in
cytopenias with these agents. Second-generation
immunomodulatory agents, such as
pomalidomide, have shown efficacy in
myelofibrosis-associated
anemia within multiple clinical trials. Five major pomalido-mide clinical trials have been completed to date, and demonstrate tolerability and efficacy with low-dose
pomalidomide (0.5 mg/day) in the treatment of
myelofibrosis, and no clinical benefit of elevated dosing regimens (≥2.5 mg/day).
Anemia responses ranged from 17% to 36% as per the International Working Group for
Myelofibrosis Research and Treatment consensus guidelines, while improvements in
splenomegaly were rare, and observed in <1% of most clinical trials. In comparison with earlier
immunomodulatory agents,
pomalidomide was associated with an improved toxicity profile, with substantially lower rates of myelosuppression and neuropathy. Given the low overall response rate to
pomalidomide as a single agent, combination strategies are of particular interest for future studies.
Pomalidomide is currently being tested in combination with
ruxolitinib, and other novel combinations are likely on the horizon.