Lenalidomide Plus Rituximab Appears Promising as First-Line Therapy for Mantle Cell Lymphoma


Key Points

  • A phase II study evaluating the combination of lenalidomide and rituximab as front-line therapy for mantle cell lymphoma has found the therapy to be effective, achieving durable responses in most patients, and providing patients with improved quality of life.
  • In this study, 92% of patients’ tumors shrank by more than half, and 64% achieved complete remission. In addition, the 2-year progression-free survival rate was estimated to be 85%, and 2-year overall survival was 97%.
  • While additional clinical trials are needed to investigate long-term outcomes of patients undergoing lenalidomide-plus-rituxan therapy, this study’s results suggest a potential strategy for developing less toxic therapies to treat mantle cell lymphoma.

Mantle cell lymphoma, which is characterized by CD5-positive, CD23-negative follicular mantle B cells with t(11:14)(q13;q32) translocation and cyclin D1 overexpression, is generally incurable and associated with a median survival of between 4 and 5 years. Although front-line treatment for mantle cell lymphoma is not standardized, it usually includes cytotoxic chemotherapy, which can be clinically challenging for patients, who are usually older and may find the side effects from high-dose chemotherapy and hematopoietic cell transplantation difficult to manage.

To determine whether the initial management of mantle cell lymphoma using biologic agents might offer effective disease control and fewer side effects than chemotherapy approaches, a phase II study by Ruan et al was launched to evaluate the efficacy and safety of the combination of lenalidomide (Revlimid) and rituximab (Rituxan) as induction and maintenance therapy in patients with previously untreated mantle cell lymphoma. The study was published in The New England Journal of Medicine.

Study Methodology

The researchers conducted a single-group, multicenter phase II trial with induction and maintenance phases. A total of 38 patients with untreated mantle cell lymphoma were enrolled in the study from July 2011 through April 2014. The median age was 65, all patients had stage III or IV disease, and the proportions of participants with low-risk, intermediate-risk, and high-risk disease at baseline were similar: 34%, 34%, and 32%, respectively.

During the induction phase, lenalidomide was administered at a dose of 20 mg daily on days 1 through 21 of every 28-day cycle for 12 cycles; the dose was escalated to 25 mg daily after the first cycle if no dose-limiting adverse events occurred during the first cycle and was reduced to 15 mg daily during the maintenance phase. Rituximab was administered once weekly for the first 4 weeks and then once every other cycle until disease progression.

The primary endpoint was overall response rate. Secondary endpoints included outcomes related to safety, survival, and quality of life.

Study Findings

At a median follow-up of 30 months (through February 2015), the overall response rate among evaluable participants was 92% (95% confidence interval [CI] = 78%–98%), and the complete response rate was 64% (95% CI = 46%–79%); median progression-free survival had not been reached. The 2-year progression-free survival was estimated to be 85% (95% CI = 67%–94%), and the 2-year overall survival 97% (95% CI = 79%–99%). A response to treatment was associated with improvement in quality of life.

The most common grade 3 or 4 adverse events were neutropenia (50%), rash (29%), thrombocytopenia (13%), an inflammatory syndrome, or “tumor flare” (11%), anemia (11%), serum sickness (8%), and fatigue (8%).

Preserving Quality of Life

“For patients, their quality of life was preserved or improved, and that’s a huge step up from regular chemotherapy,” said Jia Ruan, MD, PhD, Associate Professor of Clinical Medicine at Weill Cornell Medicine in New York, and lead author of this study, in a statement. “With this front-line treatment, we were able to achieve a very high quality and durable response rate without needing to use chemotherapy. It’s very meaningful for the patients who have always been told that their disease is without a cure.”

Dr. Ruan is a corresponding author for The New England Journal of Medicine article.

Funding for this study was provided by Celgene Corporation and a Weill Cornell Medical College Clinical Translational Science Center Grant. For full disclosures of the study authors, visit

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