Expanding on the efficacy shown in numerous single-group studies, a phase II study published in The Lancet Oncology showed lenalidomide significantly increased progression free survivalin patients with relapsed or refractory mantle cell lymphoma.
The LancetOncologyshowed the immunomodulatory agent lenalidomide significantly increased progression free survival (PFS) in patients with relapsed or refractory mantle cell lymphoma (MCL) when compared with investigator's choice of single-agent therapy.
Data from the study showed that patients enrolled in the lenalidomide arm had an average PFS of 8.7 months (95% CI, 5.5-12.1) while patients enrolled in the investigator's choice arm had an average PFS of 5.2 months (95% CI, 3.76.9). This benefit represented a 39% improvement 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= .004).
"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," said lead author Marek Trněný, Department of Hematology, Charles University Hospital, 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 trial, dubbed MCL-002, consisted of 254 patients within the intent-to-treat population for MCL. Of the 254 patients enrolled, 170 and were assigned to the lenalidomide arm while the remaining 84 were treated with an investigator's choice of monotherapy. For this study, investigator's choice consisted of rituximab, gemcitabine, fludarabine, chlorambucil, or cytarabine. Patients enrolled in the study had a median age of 68.5 years and had received an average of 2 prior regimens.
Lenalidomide was self-administered at a 25 mg dose orally 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 six cycles.
Rituximab was given to 27 patients at 375 mg/m2intravenously on days 1, 8, 15, and 22, followed by administration once every 56 days. Gemcitabine was administered to 20 patients at 1000 mg/m2intravenously on days 1, 8, and 15 of a 28-day cycle. Fludarabine was given to 18 patients at 25 mg/m2intravenously or 40 mg/m2orally on days 1 through 5 on a 28-day cycle. Eleven patients received chlorambucil at 40 mg/m2orally, given monthly over the course of 3 to 10 days. Eight patients received cytarabine at 1 or 2 g/m2intravenously once or twice daily on days 1 and 2 of a 28-day cycle.
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 move on to lenalidomide post-progression.
An objective response rate (ORR) 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 (CR) 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 ten points or more) in primary or secondary quality of life domains from baseline through the last treatment cycle was recorded with lenalidomide," Trněný 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 8.418.6). 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 best response time was not reached in the investigator's choice arm.
The most common grade 3 and 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 Trněný in the study.