Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas

Authors

  • Tahamtan Ahmadi MD, PhD,

    1. Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania
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    • The first two authors contributed equally to this work.

  • Elise A. Chong MD,

    1. Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania
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    • The first two authors contributed equally to this work.

  • Amanda Gordon BSN, CRNP,

    1. Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Nicole A. Aqui MD,

    1. Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Sunita D. Nasta MD,

    1. Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Jakub Svoboda MD,

    1. Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Anthony R. Mato MD, MSCE,

    1. Chronic Lymphocytic Leukemia Program, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey
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  • Stephen J. Schuster MD

    Corresponding author
    1. Lymphoma Program, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania
    • Corresponding author: Stephen J. Schuster, MD, Perelman Center for Advanced Medicine, 2 West Pavilion, Room 2-393S, 3400 Civic Center Boulevard, Philadelphia, PA 19104; Fax: (215) 662-4064; stephen.schuster@uphs.upenn.edu

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  • The authors thank Frannie and Jim Maguire and Margarita Louis-Dreyfus for their support of the Lymphoma Program at the Abramson Cancer Center of the University of Pennsylvania.

Abstract

BACKGROUND

Lenalidomide is an immunomodulatory drug with effects on the immune system that may enhance antibody-dependent cell-mediated cytotoxicity and reverse tumor-induced immune suppression. Furthermore, single-agent lenalidomide has therapeutic activity in relapsed/refractory B-cell lymphomas. These immunologic effects potentially may enhance the action of rituximab.

METHODS

To test the efficacy of lenalidomide combined with rituximab, the authors conducted a phase 2 trial of lenalidomide, low-dose dexamethasone, and rituximab in patients who had rituximab-resistant, relapsed/refractory, indolent B-cell or mantle cell lymphomas. Patients received two 28-day treatment cycles of lenalidomide 10 mg daily and dexamethasone 8 mg once weekly (part I). During cycle 3, 4 weekly doses of rituximab 375 mg/m2 were administered with lenalidomide-dexamethasone (part II). After the part II response assessment, stable or responding patients continued to receive lenalidomide-dexamethasone.

RESULTS

Twenty-seven patients with follicular (n = 18), mantle cell (n = 5), small lymphocytic (n = 3), and marginal zone (n = 1) lymphomas started therapy; 3 of 27 patients discontinued therapy because of adverse events and were not evaluable for response. For 24 patients, the overall response rate after part I was 29% (4 patients had a complete response [CR] or CR unconfirmed, and 3 patients had a partial response), and the overall response rate after part II was 58% (8 patients had a CR, and 6 patients had a partial response). For 27 patients, at a median follow-up of 12.2 months, the median progression-free survival was 23.7 months.

CONCLUSIONS

The combination of lenalidomide, low-dose dexamethasone, and rituximab achieved high response rates with durable responses in patients with rituximab-resistant, indolent B-cell and mantle cell lymphomas. Overall response rate increased from 29% after two 28-day cycles of lenalidomide and low-dose dexamethasone to 58% after the addition of rituximab, suggesting that lenalidomide can overcome resistance to rituximab. Cancer 2014;120:222–228. © 2013 American Cancer Society.

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