Roxanne Nelson

December 20, 2012

ATLANTA, Georgia — Lenalidomide (Revlimid), an immunomodulatory agent approved for use in multiple myeloma, has shown promise in the treatment of mantle cell lymphoma (MCL), one of the rarest non-Hodgkin's lymphomas.

In a very large phase 2 trial, lenalidomide showed "rapid and durable efficacy" in the treatment of MCL, and the safety profile "is what you'd expect," said lead author Andre Goy, MD, MS, chair, director, and chief of lymphoma at the John Theurer Cancer Center in Hackensack, New Jersey. He presented the results here at the American Society of Hematology 54th Annual Meeting.

"The study is a confirmation, but it also offers a platform for future studies of combination therapies," he explained.

The study participants were "very heavily pretreated and had a median of 4 previous therapies; this is a very difficult population of patients," Dr. Goy told Medscape Medical News.

MCL accounts for about 6% of all non-Hodgkin's lymphomas. Despite advances in treatment, most patients will relapse over time. In addition, patients who relapse often develop chemoresistance, and thus have a poor overall prognosis. "There is only one drug approved so far for mantle cell lymphoma — bortezomib (Velcade). In clinical trials, it showed a response rate of 33%," said Dr. Goy.

For MCL patients with relapsed or progressive disease who have progressed after or were refractory to bortezomib, lenalidomide might provide a new therapeutic option, he said.

Activity in Lymphoma

Lenalidomide has demonstrated tumoricidal and antiproliferative effects in MCL and clinical activity and safety in multiple phase 2 studies in aggressive non-Hodgkin's lymphoma. "Phase 2 trials have shown activity across the board in lymphomas with lenalidomide, but especially in mantle cell lymphoma," explained Dr. Goy.

He and his colleagues enrolled 134 patients who had previously been treated with rituximab (Rituxan), cyclophosphamide, and anthracycline, and had relapsed, progressed, or were refractory to bortezomib. In this multicenter single-group open-label study, lenalidomide monotherapy 25 mg/day was administered on days 1 to 21 of a 28-day cycle until disease progression, unacceptable toxicity, or voluntary withdrawal.

All study participants were heavily pretreated; there was no limitation on the number of previous therapies. Median age was 67 years (range, 43 to 83), two thirds of the patients were 65 years or older, and 93% had advanced-stage (stage III to IV) disease.

The median number of previous therapies was 4 (range, 2 to 10); 78% had received at least 3 previous lines of treatment.

When determined by independent central review, the overall response rate was 28%, the complete response rate was 8%, and the median duration of response of 16.6 months.

When determined by investigator assessment, the overall response rate was 32%, the complete response rate was 16%, and the median duration of response was 18.5 months.

With central review, median time to response was 2.2 months, median time to complete response was 3.7 months, median progression-free survival was 4.0 months, and median overall survival was 19.0 months.

Remarkably, when we did a subset analysis, "we saw a response rate in the same range in every subset," said Dr. Goy.

More than a third of patients (38%) required a dose reduction, and treatment was discontinued in 19% of patients, primarily because of myelosuppression. The most common grade 3/4 adverse events were neutropenia (43%), thrombocytopenia (28%), anemia (11%), pneumonia (8%), and fatigue (7%).

Other adverse events of any grade included tumor flare reaction (10%), deep vein thrombosis (4%), pulmonary embolism (2%), and invasive second primary malignancies (2%).

This study was conducted in the relapsed setting in heavily pretreated patients, but it is feasible that lenalidomide could be used in the front-line setting. Because "many patients are diagnosed at late stage, it would be interesting to test noncytoxic options," said Dr. Goy.

Dr. Goy reports relationships with Pfizer, Seattle Genetics, J&J, Pharmacyclics, and Celgene. Several of his coauthors report relationships with industry, as noted in the abstract.

American Society of Hematology (ASH) 54th Annual Meeting: Abstract 905. Presented December 11, 2012.