Treatment with lenalidomide (Revlimid) as initial therapy induced long-lasting responses in a phase II study of 60 patients with chronic lymphocytic leukemia (CLL). “Overall, 35 patients (58%) patients had responses lasting more than 36 months and were considered long-term responders,” the researchers wrote in Blood.
Best responses among long-term responders were 25 complete remissions (71% of patients), including five patients with no evidence of residual disease at bone marrow evaluation (minimal residual disease–negative complete remissions), and 10 partial remissions (29% of patients). At a median follow-up of 4 years, median time to treatment failure had not been reached and overall survival was 82%. All of the long-term responders are alive, the researchers noted, and 25 of the long-term responders are still on therapy.
“Treatment consisted of 5 mg of lenalidomide daily by mouth, continuously. After two 28-day cycles, the dose of lenalidomide could be escalated by increments of 5 mg per cycle to 25 mg daily,” the investigators explained.
Previously reported results showed an overall response rate of 56% with 2-year overall survival of 88% and progression-free survival of 60%. “Because response duration and long-term survival are important clinical endpoints, we sought to report the long-term outcome of this trial,” the authors wrote.
“As patients continued on therapy with lenalidomide, we compared the quality of responses at 18 months and after 36 months. Twelve patients with a [partial remission] improved their response to a [complete remission], 8 patients with stable disease improved their response to [partial remission], and 2 additional patients achieved [minimal residual disease]-negative [complete remission],” the investigators reported.
Hematologic toxicity led to dose reductions. Ten long-term responders discontinued lenalidomide, six because of toxicity, two due to moderate neuropathy, and one each due to deep venous thrombosis, persistent fatigue, moderate weight loss, and immune thrombocytopenia. Other reasons for discontinuation were progression, sepsis, second malignancy (invasive squamous cell carcinoma of the skin), and change of institution.
“Recent reports have suggested a possible correlation between treatment with lenalidomide and the development of second cancers in patients with multiple myeloma,” the authors noted. “In our series only 1 patient developed an invasive skin cancer, but the size of this study and the available follow up time are insufficient to derive accurate information on the occurrence of other cancers.” ■
Strati P, et al: Blood. June 25, 2013 (early release online).