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Phase II study of bendamustine combined with rituximab in relapsed/refractory mantle cell lymphoma: efficacy, tolerability, and safety findings

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Abstract

In most cases of relapsed/refractory mantle cell lymphoma (MCL), patients respond to salvage therapy, though typically responses are partial and/or transient followed by disease progression, even with newer agents (e.g., ibrutinib). In this multicenter, open-label, single-arm, phase II study, patients with relapsed/refractory non-blastoid MCL received bendamustine 90 mg/m2 (days 1 and 2) and rituximab 375 mg/m2 (day 1) for 6 planned 28-day cycles. Functional imaging with 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) was conducted at baseline and after cycle 6. Forty-five patients were enrolled (median age, 70 years; 82 % stage IV disease; median number of prior chemotherapies, 2 [range, 1–4]), showing an overall response rate (ORR; primary efficacy measure) of 82 % (complete response [CR], 40 %; partial response, 42 %). In the 32 patients with complete 18F-FDG PET/CT data, 75 % achieved a complete metabolic response. Median duration of response was 1.6 years, 1-year progression-free survival was 67 %, and 3-year overall survival was 55 %. Main non-hematologic adverse events were nausea (69 %), fatigue (56 %), decreased appetite (42 %), constipation (38 %), diarrhea (36 %), vomiting (36 %), and decreased weight (31 %). Grade 3/4 neutropenia and lymphopenia occurred in 44 and 89 % of patients, respectively. ORR and CR rate compared favorably with single-agent ibrutinib (ORR, 67 %; CR, 23 %); bendamustine-rituximab is an effective therapy with manageable toxicity in relapsed/refractory MCL.

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Acknowledgments

This research was sponsored by and conducted by Teva Branded Pharmaceutical Products R&D, Inc., Frazer, PA. Statistical support was provided by Ling Chen, PhD (Teva Branded Pharmaceutical Products R&D, Inc.). Medical writing assistance (including literature searches, editing and fact checking, graphic support, and at the request of and with guidance from the authors, assistance with the preparation of the outline and drafting of this manuscript) was provided by The Curry Rockefeller Group, LLC, Tarrytown, NY, and was funded by Teva Branded Pharmaceutical Products R&D, Inc. (Frazer, PA). Teva provided a full review of the article. We wish to thank all the site investigators who contributed to this study and their staff for their support, as well as all the patients and their families for their dedication to research and this study. A special thank you is also given to Glen Davis and Coleen Myers from Teva Branded Pharmaceutical Products R&D, Inc., for their complete dedication in ensuring the data collection was available adequately.

Conflict of interest

The authors received research funding for this study from Teva Pharmaceutical Products R&D, Inc. MSC has served as consultant to Teva Pharmaceuticals and Mundipharma, and has received an honorarium for serving as an educational meeting chairman for Mundipharma. AG has served as a member of the Board of Directors/advisory committees of Pharmacyclics, JNJ, Celgene, and Millennium; participated in the speakers’ bureaus of Pharmacyclics, JNJ, Celgene, and Millennium; and served as a consultant for and received honoraria from Celgene. He has also received research funding for clinical trials through his institution. DL and DAG declare that they have no conflict of interest. MCM is an employee and shareholder of Teva, and has owned stock/held an ownership interest in Janssen. RHvdJ has served as a consultant for, participated in speakers’ bureaus for, and has received honoraria and research funding from Teva Pharmaceuticals and Lundbeck.

Research involving human participants and/or animals

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Author information

Author notes

  1. D. A. Graf

    Present address: University of Texas Medical Branch at Galveston, Galveston, TX, 77555, USA

Authors and Affiliations

  1. Department of Medicine, Elm and Carlton Streets, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA

    Myron S. Czuczman

  2. Lymphoma Division, Hackensack University Medical Center, Hackensack, NJ, 07601, USA

    A. Goy

  3. Department of Nuclear Medicine, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA

    D. Lamonica & D. A. Graf

  4. Teva Branded Pharmaceutical Products R&D, Inc., Frazer, PA, 19355, USA

    M. C. Munteanu

  5. Department of Medicine, The Ottawa Hospital, General Campus, K1H 8L6, Ottawa, Canada

    R. H. van der Jagt

Authors
  1. Myron S. Czuczman
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  2. A. Goy
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  3. D. Lamonica
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  4. D. A. Graf
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  5. M. C. Munteanu
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  6. R. H. van der Jagt
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Corresponding author

Correspondence to Myron S. Czuczman.

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Czuczman, M.S., Goy, A., Lamonica, D. et al. Phase II study of bendamustine combined with rituximab in relapsed/refractory mantle cell lymphoma: efficacy, tolerability, and safety findings. Ann Hematol 94, 2025–2032 (2015). https://doi.org/10.1007/s00277-015-2478-9

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  • DOI: https://doi.org/10.1007/s00277-015-2478-9

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