Lenalidomide Approved by the FDA for the Treatment of Mantle Cell Lymphoma

Mantle cell lymphoma is a type of B-cell non-Hodgkin lymphoma that occurs in less than 10% of all cases of non-Hodgkin lymphoma. Malignant cells that originate in the lymph nodes may spread through the blood or lymph system to other sites to develop extranodal disease in the spleen, bone marrow, liver, or gastrointestinal tract.

Lenalidomide is an analog of thalidomide with antiangiogenic, antitumorigenic, and immunomodulating activity. Previously, the drug received approval for the treatment of multiple myeloma and myelodysplastic syndrome.

“There remains a tremendous unmet need for patients with previously-treated mantle cell lymphoma,” said Andre Goy, MD, Chairman and Director and Chief of Lymphoma at John Theurer Cancer Center at Hackensack UMC in Hackensack, New Jersey, Chief Science Officer and Director of Research and Innovation at Regional Cancer Care Associates, LLC, and lead author of the MCL-001 study. “The approval of lenalidomide delivers a new option, and the first oral therapy in this area of lymphoma.”

The expanded approval was based on positive results from a phase II, multicenter, single arm, open label study that were presented at the 54th American Society of Hematology (ASH) Annual Meeting and Exposition, held in December 2012, in Atlanta.

The MCL-001 study enrolled 134 patients with MCL who had received prior treatment with cyclophosphamide, rituximab, an anthracycline (or mitoxantrone), and bortezomib alone or in combination and who had documented relapsed or refractory disease. Patients with a higher level of creatinine (&ge;60mL/min) received 25 mg of lenalidomide once daily for 21 days every 28 days, and patients with lower levels of creatinine (&ge;30mL/min and <60mL/min) received 10 mg of lenalidomide once daily for 21 days every 28 days. The primary endpoint of the study was overall response rate (ORR).

As reported by an independent review, the ORR was 26% (34/133; 95% CI, 18.4—33.9), and the complete response rate was 7% (9/133; 95% CI, 3.1&ndash;12.5). The median duration of response to the drug was 16.6 months (95% CI, 7.7&ndash;26.7). According to the manufacturer of lenalidomide, Celgene, these results vary from the data first presented at the ASH meeting because the FDA conducted their own review of the data and wound up with similar but slightly different results. The most common grade 3 or 4 adverse events that were reported in at least 5% of patients included neutropenia (43%), thrombocytopenia (28%), anemia (11%), pneumonia (9%), fatigue (7%), leukopenia (7%), febrile neutropenia (6%), diarrhea (6%), and dyspnea (6%).

Goy said that further analysis of data from the studies on lenalodimide in mantle cell lymphoma have confirmed that the durable response is observed across all patient subgroups.

&ldquo;There is currently ongoing investigation to see if we can move the drug into an earlier setting and whether it works well in combination with other agents for this disease,&rdquo; Goy said.

In addition to the approval at a recommended dose of 25 mg once daily of lenalidomide, the supplemental application also included an approval for a new 20 mg strength capsule of the drug.