Progression-Free Survival in CLL Prolonged With Maintenance Lenalidomide
For patients with CLL who do not achieve MRD negative disease state following first-line chemoimmunotherapy, lenalidomide may hamper disease prgression.
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.”