Combination Biologic Therapy Without Chemotherapy as Initial Treatment for Mantle-Cell Lymphoma: Multicenter Phase 2 Study of Lenalidomide Plus Rituximab

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Lenalidomide, an immunomodulatory compound that targets both tumor cells and the tumor microenvironment, has shown clinical efficacy either alone or in combination with rituximab in relapsed mantle-cell lymphoma (MCL).1,2 In this study, Ruan and colleagues reported findings from a chemotherapy-free treatment for untreated MCL, which included the combination lenalidomide plus rituximab.3

The primary objective of the study was to evaluate the overall response rate associated with lenalidomide plus rituximab treatment. A total of 32 patients with untreated MCL were enrolled at 4 centers. At the study entry, more men than women were enrolled and the patients’ median age was 65 years. All patients had stage III or IV disease. Overall, 40% of patients had elevated lactate dehydrogenase levels, and 88% of patients had bone marrow involvement.3

During the induction phase of the study protocol, lenalidomide was administered at a starting dose of 20 mg daily on days 1 to 21 of a 28-day cycle for a total of 12 cycles; dose escalation to 25 mg daily was allowed if tolerated. Standard-dose rituximab was administered weekly for 4 weeks during cycle 1, and then once every other cycle for a total of 9 doses. During the maintenance phase (which started with cycle 13), lenalidomide was dosed at 15 mg daily on days 1 to 21 of a 28-day cycle, and rituximab maintenance was given once every other cycle until disease progression.3
           
Treatment with lenalidomide plus rituximab was generally well tolerated. Grade 3 or 4 hematologic adverse events included neutropenia, thrombocytopenia, and anemia. Grade 3 or 4 nonhematologic adverse events were rare, and included rash, tumor flare, and serum sickness associated with rituximab. In addition, 1 deep vein thrombosis and 1 pulmonary embolism were observed but resolved with treatment. No secondary malignancies were noted.3

After a median follow-up of 16 months, 28 of the 32 patients remained on lenalidomide plus rituximab therapy without evidence of disease progression, including 18 patients who had completed induction and who were receiving lenalidomide plus rituximab maintenance.3

Thirty patients were evaluable for efficacy with at least 1 response assessment. The preliminary overall response rate for evaluable patients was 87%, including 57% of patients who achieved complete response (CR) and CR unconfirmed. The median time to CR was 11 months, with response typically confirmed between 6 and 12 months. Of note, response quality improved over time on therapy.3

The median progression-free survival and the duration of response have not been reached. The 1-year progression-free survival was estimated at 93% after a median follow-up of 16 months. The overall survival was 100% at the time of data presentation. All patients have maintained or improved the quality-of-life parameters during treatment.3

This study demonstrates that a chemotherapy-free combination is feasible as initial therapy for patients with MCL. Preliminary safety and efficacy data are encouraging, justifying further evaluation of the lenalidomide plus rituximab regimen alone and in combination with novel agents in both patients with untreated and relapsed MCL.3

References:

  1. Goy A, Sinha R, Williams ME, et al. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. J Clin Oncol. 2013;31:3688-3695.
  2. Wang M, Fayad L, Wagner-Bartak N, et al. Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Lancet Oncol. 2012;13:716-723.
  3. Ruan J, Martin P, Bijal SD, et al. Combination biologic therapy without chemotherapy as initial treatment for mantle cell lymphoma: multi-center phase II study of lenalidomide plus rituximab.  Oral presentation at: American Society of Hematology (ASH) 2013 Annual Meeting; December 7-10, 2013; New Orleans, LA. Abstract 247.
Last modified: March 25, 2014
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