Lenalidomide

The U.S. Food and Drug Administration (FDA) approved lenalidomide for the treatment of lower-risk, transfusion-dependent patients with MDS who harbor a del(5q) cytogenic abnormality. In a phase II registration study of 148 transfusion-dependent low-risk and intermediate-1–risk patients with del(5q) chromosomal abnormalities (alone, or associated with other abnormalities), lenalidomide induced transfusion independence in 67%, with a median time to response of 4 to 5 weeks.[13] The median duration of transfusion independence had not been reached after a median of 104 weeks of follow-up. Of 62 evaluable patients, 38 patients developed complete cytogenetic remission.

Lenalidomide administration is limited by dose-limiting neutropenia and thrombocytopenia.[14][Level of evidence C3] Treatment-related thrombocytopenia also correlated with cytogenetic responses, emphasizing the importance of successful suppression of the del(5q) clone with lenalidomide to achieve meaningful responses.[15]

A subsequent phase III study randomly assigned lower-risk del(5q) MDS patients to receive placebo and lenalidomide at either 5 mg daily for 28 days or 10 mg daily for 21 days of a 28-day cycle.[16] Transfusion independence responses lasting longer than 6 months occurred in 43% to 52% of subjects treated on the lenalidomide arms, compared with 6% of controls. The cytogenetic response rate was 25% to 50% on the active treatment arms, and the 3-year risk of AML transformation was 25%.

Lenalidomide has limited activity in lower-risk, red blood cell transfusion–dependent patients in MDS who do not harbor the del(5q) lesion. In a phase II study similar in design to the registration study, 56 of 215 patients (26%) achieved transfusion independence.[17] Median duration of response was 41 weeks (range, 8–136 weeks). Grade 3 or 4 myelosuppression occurred in only 20% to 25% of patients and, unlike for del(5q) patients, was not associated with subsequent attainment of a transfusion independence response to therapy.