EC Approves Lenalidomide for Relapsed/Refractory Mantle Cell Lymphoma

Marek Trneny, MD

The European Commission (EC) has approved lenalidomide (Revlimid) for use as a treatment for patients with relapsed or refractory mantle cell lymphoma (MCL).

The approval was based on data from the phase II MCL-002 trial in which lenalidomide reduced the risk of progression or death by 39% versus investigator's choice of therapy. The EC decision follows a positive opinion issued by the European Medicines Agency’s Committee for Medicinal Products for Human Use.

"New treatment options are vitally needed in order to change the course of MCL for patients, given the severity of the disease, and there are still limited existing treatment options," lead MCL-002 author Marek Trneny, MD, department of hematology, Charles University Hospital, in Prague, said in a statement. "Lenalidomide is a proven medicine that has shown efficacy in relapsed/refractory MCL, with the MCL-002 study meeting its primary endpoint of an improvement in progression-free survival."

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 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 median progression-free survival was 8.7 months (95% CI, 5.5-12.1) with lenalidomide versus 5.2 months (95% CI, 3.7—6.9) in the investigator’s choice arm (HR, 0.61; 95% CI, 0.44-0.84; P = .004).

The objective response rate was 40% in the lenalidomide cohort versus 11% in patient’s treated with investigator's choice. Additionally, 5% of patients in the lenalidomide arm experienced a complete response versus 0% in the investigator's choice arm.

Median duration of response was 16.1 months (95% CI, 9.5-20.0) with lenalidomide versus 10.4 months (95% CI 8.4-18.6) in the investigator's choice cohort. 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.

Frequently occurring all-grade adverse events (AEs) in the lenalidomide arm included neutropenia (50.9%), anemia (28.7%), diarrhea (22.8%), fatigue (21.0%), constipation (17.4%), pyrexia (16.8%), and rash (16.2%).

The most common grade 3/4 AEs for the lenalidomide versus investigator’s choice arms were neutropenia (43% vs 33%, respectively), thrombocytopenia (18% vs 27%), and anemia (8% vs 7%).

Beyond MCL, lenalidomide also has approved indications in Europe for the treatment of patients with multiple myeloma. In the United States, lenalidomide has approved indications for MCL, multiple myeloma, and myelodysplastic syndromes.

Trneny 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. 2016;17(3):319-331.