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Biologic Doublet a Potential Front-Line Treatment in Mantle Cell Lymphoma

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Key Points

  • As the initial treatment of mantle cell lymphoma, a chemotherapy-free regimen of lenalidomide plus rituximab achieved an 87% response rate, and 57% achieved a complete response in a multicenter phase II study.
  • Estimated 1-year progression-free survival was 93%, and the regimen was well tolerated.

A high proportion of mantle cell lymphoma patients may achieve an objective and durable response to treatment with an initial chemotherapy-free regimen, according to Jia Ruan, MD, PhD, of Weill Cornell Medical College, New York, who presented the results of a multicenter phase II study at the 55th American Society for Hematology (ASH) Annual Meeting and Exposition (Abstract 247).

At a median follow-up of 16 months in 30 evaluable patients, the objective response rate was 87%, with 57% of patients achieving a complete response. The response quality appeared to improve over the course of therapy, Dr. Ruan reported.

“The initial treatment of mantle cell lymphoma is not standardized. Current conventional upfront chemoimmunotherapies are generally not curative and can be deferred in some patients. This presents an opportunity to evaluate novel therapeutic approaches in the first-line setting,” she said.

Lenalidomide (Revlimid) targets both the tumor cells directly and the tumor microenvironment and is active in recurrent mantle cell lymphoma. As a single agent in relapsed mantle cell lymphoma, lenalidomide has produced responses in 28% of patients, rising to 57% when given in combination with rituximab (Rituxan), she noted.

“But prior studies of the initial treatment of mantle cell lymphoma have focused on the use of chemotherapy,” she said. “We hypothesized that a biologic, nonchemotherapy approach would be a well tolerated and active strategy as initial therapy for mantle cell lymphoma.”

Study Details

The study included 32 untreated mantle cell lymphoma patients, about one-third of whom were low-risk, one-third intermediate-risk, and one-third high-risk patients who refused or were not candidates for chemotherapy. Symptomatic lymphadenopathy was the main indication for treatment (44%).  

The induction phase included lenalidomide at 20 mg daily on days 1 to 21 of a 28-day cycle for a total of 12 cycles, with dose escalation to 25 mg daily if tolerated. The standard dose of rituximab was given weekly for four treatments during cycle 1, then once every other cycle, for a total of nine doses. During the maintenance phase, starting with cycle 13, lenalidomide was given at 15 mg daily on days 1 to 21 of a 28-day cycle, with rituximab given as maintenance once every other cycle until progression of disease.

Encouraging Progression-Free and Overall Survival

The high response rates translated into encouraging progression-free and overall survival. At a median follow-up of 16 months, the 12-month progression-free survival was estimated at 93%, and overall survival was estimated at 100%, Dr. Ruan reported.

“All subjects remain alive as of last follow-up,” she said.

Responses improved over time, with complete responses increasing from just over 10% at 6 months to more than 50% by 21 months.

Forty percent of patients required a dose reduction, usually to 15 mg of lenalidomide daily; 17% tolerated an escalation of the lenalidomide dose to 25 mg.

The treatment was tolerable, with the primary toxicities related to inflammation, including grade ≥ 3 rash (22%), fatigue (9%), and tumor flare (9%). “The symptoms were completely related to inflammatory syndromes. These can be concerning to the patient, but they tend to occur in cycle 1. After their initial assessment, patients [appear to do well],” Dr. Ruan noted.

“We believe our findings justify further evaluation of the lenalidomide plus rituximab regimen, both alone and as a platform in combination with other novel agents in mantle cell lymphoma therapy, and in both the upfront and relapsed settings,” she said.

For full disclosures of the study authors, view the study abstract on the ASH website.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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