Lenalidomide may reduce the relative risk of disease progression among patients with chronic lymphocytic leukemia (CLL) who do not achieve minimal residual disease (MRD) negative disease state after first-line chemoimmunotherapy, according to a study published in The Lancet.
Previous studies demonstrated that high MRD or a combination of intermediate MRD with select gene mutations were characteristics found in patients at high risk of early disease progression after first-line therapy. The purpose of this study was to evaluate the effectiveness of lenalidomide as maintenance therapy in patients with CLL identified as high risk by a MRD-based algorithm.
For the phase 3 CLLM1 study (ClinicalTrials.gov Identifier: NCT01556776), researchers randomly assigned 89 patients with CLL who were considered to be high-risk to receive lenalidomide 5 mg with possible escalation or placebo. Patients received a median of 11.0 treatment cycles by time of data cutoff.
Patients in the lenalidomide arm did not reach median PFS (95% CI, 32.3–not evaluable) after median observation time of 17.9 months compared with 13.3 months (95% CI, 9.9–19.7) in the placebo group (hazard ratio [HR], 0.168; 95% CI, 0.074-0.379; P <.0001).
The most frequently reported adverse events (AEs) were skin disorders (63% vs 28% in the lenalidomide and placebo groups, respectively), gastrointestinal disorders (61% vs 28%), infections (54% vs 66%), hematologic toxicities (50% vs 17%), and general disorders (50% vs 31%).
One case of fatal acute lymphocytic leukemia occurred in the lenalidomide arm, and 1 patient in the placebo arm died of fatal multifocal leukoencephalopathy.
Study authors state that given the promising results of the study, lenalidomide should be further evaluated in patients with high-risk CLL, and concluded that “the findings of this study confirm the prognostic significance of the minimal residual disease-based risk assessment model, which might be used in future trials.”