Retrospective Analysis of the Clinical Use and Benefit of Lenalidomide and Thalidomide in Myelofibrosis.

Introduction: Anemia in myelofibrosis (MF) occurs frequently, is poorly addressed by US Food and Drug Administration-approved JAK inhibitors, and negatively impacts quality of life. Immunomodulatory imide agents (IMiDs) such as thalidomide and lenalidomide are among the limited treatment options that have demonstrated anemia benefit in single-arm studies.

Patients And Methods: To better understand the comparative impact of lenalidomide and thalidomide in MF patients, we analyzed 176 consecutive MF patients who received lenalidomide or thalidomide for at least 4 weeks. We sought to understand the variability in patient populations receiving lenalidomide versus thalidomide, to assess the efficacy of these agents, and to investigate clinical or genomic features that predict response.

Results: Clinical benefit (CB) was assessable in 83 lenalidomide- and 67 thalidomide-treated patients. Thalidomide-treated patients were more likely to have thrombocytopenia (P < .001) and high-risk disease (P = .02). Forty-one (49%) lenalidomide-treated patients were deemed to have CB, predominantly due to anemia benefit. Similarly, 28 (42%) of thalidomide-treated patients had CB attributable to anemia benefit. Overall survival was similar for lenalidomide- and thalidomide-treated patients (P = .51). Lenalidomide-treated patients with CB had longer overall survival than those who did not (P = .01). High-risk mutations were found in 12 (41%) of 29 and 20 (57%) of 35 patients treated with lenalidomide and thalidomide, respectively (P = .32). Splicing mutations were common in both cohorts, though thalidomide-treated patients were more likely to have a high-risk SRSF2 or U2AF1 Q157 mutation (P = .01).

Conclusion: Overall, in this retrospective analysis, lenalidomide and thalidomide showed similar rates of CB in a cohort of MF patients that frequently harbored splicing mutations.