Marek TrnÄ›ný, MD
Lenalidomide (Revlimid) was found to significantly increase progression-free survival (PFS) in patients with relapsed/refractory mantle cell lymphoma (MCL) when compared with investigator's choice of single-agent therapy, according to results of a phase II study published in The Lancet Oncology
Data from the study, which was expanded from the efficacy in various single-group studies, showed that patients enrolled in the lenalidomide arm had a median PFS of 8.7 months (95% CI, 5.5-12.1) versus 5.2 months in the investigator's choice arm (95% CI, 3.7–6.9). This benefit represented a 39% reduction in the risk of progression or death in the lenalidomide arm versus investigator's choice (HR, 0.61; 95% CI, 0.44-0.84; P
"In the MCL-002 study, lenalidomide treatment resulted in a significant improvement in progression-free survival compared with the investigator's choice of single-agent therapy in patients with relapsed or refractory mantle cell lymphoma," lead author Marek TrnÄ›ný, MD, Department of Hematology, Charles University Hospital, said in the study. "The significant improvement in progression-free survival was observed despite a worse baseline prognostic profile in the lenalidomide group."
The randomized, multicenter phase II MCL-002 trial enrolled 254 patients within the intent-to-treat population for MCL. Of the 254 patients, 170 received lenalidomide while the remaining 84 were treated with an investigator's choice of monotherapy, which included rituximab, gemcitabine, fludarabine, chlorambucil, or cytarabine. Patients had a median age of 68.5 years and received an average of 2 prior regimens.
Lenalidomide, an immunomodulatory agent, was self-administered orally at 25 mg on days 1 through 21 of each 28-day cycle until disease progression or presentation of toxicities. Lenalidomide was given in 10-mg doses in patients with creatinine clearance between ≥30 mL/min and <60 mL/min. In the investigator’s choice arm, chlorambucil and rituximab were administered until progression, resistance, or withdrawal by the patient. Cytarabine, fludarabine, and gemcitabine were given for 6 cycles.
Rituximab was given to 27 patients at 375 mg/m2
intravenously on days 1, 8, 15, and 22, followed by administration once every 56 days. Gemcitabine was administered to 20 patients at 1000 mg/m2
intravenously on days 1, 8, and 15 of a 28-day cycle. Fludarabine was given to 18 patients at 25 mg/m2
intravenously or 40 mg/m2
orally on days 1 through 5 on a 28-day cycle. Eleven patients received chlorambucil at 40 mg/m2
orally, given monthly over the course of 3 to 10 days. Eight patients received cytarabine at 1 or 2 g/m2
intravenously once or twice daily on days 1 and 2 of a 28-day cycle.
The median treatment duration with lenalidomide was 24.3 weeks (IQR, 7.0-64.6) and 13.1 weeks in the investigator's choice arm (IQR, 5.4-21.9). Patients enrolled in the investigator's choice group were able to cross over to lenalidomide post-progression.
The objective response rate was 40% in the lenalidomide arm versus 11% in the investigator's choice arm. Additionally, 5% of patients in the lenalidomide arm experienced a complete response versus 0% in the investigator's choice arm.
"Patients treated with lenalidomide maintained their quality of life scores despite a longer duration of treatment compared with investigators' choice. No deterioration (change of 10 points or more) in primary or secondary quality of life domains from baseline through the last treatment cycle was recorded with lenalidomide," TrnÄ›ný said in the study. "Additionally, patients receiving lenalidomide had statistically significant higher rates of clinically meaningful improvement in quality of life for physical function and pain."
Median duration of response was 16.1 months in the lenalidomide arm (95% CI, 9.5-20.0) and 10.4 months in the investigator's choice arm (95% CI 8.4–18.6). The time to best response in the lenalidomide arm population was 6.2 months (95% CI 3.9–11.7), according to Kaplan-Meier estimates. This was not reached in the investigator's choice arm.
The most common grade 3/4 adverse events for the lenalidomide versus investigator’s choice arms were neutropenia (43% vs 33%, respectively), thrombocytopenia (18% vs 27%), and anemia (8% vs 7%).
"The key strengths of this study are that, to our knowledge, this is the first randomized study of lenalidomide in patients with relapsed or refractory mantle cell lymphoma. It compared lenalidomide with control treatments that show single-agent activity in mantle cell lymphoma, it was prospectively performed in a large number of patients from many study centers, and it provided central review assessments for efficacy," said TrnÄ›ný in the study.
TrnÄ›ný M, Lamy T, Walewski J, et al. Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial. Lancet Oncol. 2016;17(3):319-331.