FDA Approves Lenalidomide for the Treatment of Mantle Cell Lymphoma
Published Online: Wednesday, June 5, 2013
Andre Goy, MD, MS
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 in Atlanta, Georgia.
“This really does help patients who really have run out of other options,” 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.
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.
The MCL-001 study enrolled 134 patients with MCL who had received prior treatment with rituximab, cyclophosphamide, 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 (≥60mL/min) received 25 mg of lenalidomide once daily for 21 days every 28 days, and patients with lower levels of creatinine (≥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).
According to 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, 3.1–12.5). The median duration of response to the drug was 16.6 months (95% CI, 7.7–26.7). According to Celgene, the manufacturer of lenalidomide, 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.
According to the approval announcement, 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 explained that this is the first drug to receive approval for the treatment of mantle cell lymphoma since bortezomib was approved for the disease in 2006. The course of treatment varies by the age of the patient, but eventually, even patients who receive bortezomib eventually relapse. The fact that many patients achieved a durable and prolonged response was very encouraging, Goy noted.
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.
“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,” 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.
Goy A, Sinha R, Williams ME, et al. Phase II multicenter study of single-agent lenalidomide in subjects with mantle cell lymphoma who relapsed or progressed after or were refractory to bortezomib: the MCL-001 “EMERGE” study. 54th ASH Annual Meeting; December 8-11, 2012; Atlanta, GA. Abstract 905.
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