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Results of a phase II study of bendamustine and ofatumumab in untreated indolent B cell non-Hodgkin’s lymphoma

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Abstract

The efficacy/tolerability of bendamustine, a unique alkylator, plus ofatumumab, a human anti-CD20 monoclonal antibody, was evaluated for previously untreated indolent B cell non-Hodgkin’s lymphoma (NHL). The study investigated whether the overall response rate (ORR) for bendamustine-ofatumumab was similar to historical bendamustine-rituximab ORRs (≥90 %). In this multicenter, open-label, single-arm, phase II study, patients received six planned 28-day cycles of bendamustine (90 mg/m2 on days 1 and 2 of each cycle) and ofatumumab (300 mg on day 1, 1000 mg on day 8 of cycle 1, and on day 1 of subsequent cycles). The primary outcome was ORR. Secondary objectives included safety and tolerability. Exploratory evaluations included percentage of patients with positive baseline [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans who converted to negative postbaseline and quality of life (QOL) scores. The treated/safety analysis population received ≥1 dose of either therapy. The bendamustine-ofatumumab ORR was 90 % (95 % confidence interval, 77.8–96.6) in 49 treated patients (67 % complete response, 22 % partial response). No patients had progressive disease. Bendamustine-ofatumumab was acceptably tolerated. All 49 patients had ≥1 adverse event, the most common being nausea (61 %), fatigue (55 %), and infusion-related reactions (45 %, all but 1 occurring during cycle 1). The proportion of patients whose FDG-PET scans converted to negative postbaseline was 88 %. Changes in QOL scores were minor. In patients with treatment-naive, indolent B cell NHL, bendamustine-ofatumumab exhibited a high degree of activity (90 % ORR), comparable with historical bendamustine-rituximab ORRs (≥90 %), and was adequately tolerated (ClinicalTrials.gov identifier: NCT01108341).

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Acknowledgments

This research was sponsored and conducted by Teva Branded Pharmaceutical Products R&D, Inc., Frazer, PA. Ofatumumab was provided by GlaxoSmithKline, Brentford, UK. Special thanks are also given to all patients and their families, all participating sites, and research staff for their dedication to this study (see Appendix for listing of contributing investigators and participating sites). The authors thank Peter Brown (Teva) for his gracious review of this manuscript. Funding for editorial, design, and production support was provided by Teva to The Curry Rockefeller Group, LLC, Tarrytown, NY.

Conflict of interest

Myron S. Czuczman is a consultant to GlaxoSmithKline and Teva Branded Pharmaceutical Products R&D, Inc., has received honoraria from Teva, and has received research funding from Cephalon (now Teva). Andres Forero’s institution has received research funding from Cephalon (now Teva). Glen Davis is an employee of Teva. Mihaela Munteanu is an employee and shareholder of Teva and has owned stock/held an ownership interest in Janssen. Fritz Offner is a consultant to GlaxoSmithKline. Nathan Fowler is a consultant to Roche and has received research funding from Roche and Teva. Stephen Kahanic, Eric Van Den Neste, Dominique Bron, and Donald Quick declare that they have no conflict of interest.

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Authors and Affiliations

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

    Myron S. Czuczman

  2. Siouxland Hematology-Oncology Associates, 230 Nebraska Street, Sioux City, IA, 51101, USA

    Stephen Kahanic

  3. University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL, 35294, USA

    Andres Forero

  4. Teva Branded Pharmaceutical Products R&D, Inc., 41 Moores Rd, Frazer, PA, 19355, USA

    Glen Davis & Mihaela Munteanu

  5. Cliniques Universitaires (UCL) Saint-Luc, 10 av Hippocrate, Brussels, Belgium

    Eric Van Den Neste

  6. Universitair Ziekenhuis Gent, De Pintelaan 185, 9000, Ghent, Belgium

    Fritz Offner

  7. Institut Jules Bordet (ULB), 1 Rue Heger-Bordet, 1000, Brussels, Belgium

    Dominique Bron

  8. Joe Arrington Cancer Research and Treatment Center, 4010 22nd Place, Lubbock, TX, 79410, USA

    Donald Quick

  9. The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 429, Houston, TX, 77030, USA

    Nathan Fowler

Authors
  1. Myron S. Czuczman
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  2. Stephen Kahanic
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  3. Andres Forero
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  4. Glen Davis
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  5. Mihaela Munteanu
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  6. Eric Van Den Neste
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  7. Fritz Offner
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  8. Dominique Bron
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  9. Donald Quick
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  10. Nathan Fowler
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Corresponding author

Correspondence to Myron S. Czuczman.

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Online Resource 1

Change from baseline to last observation in European Organization for Research and Treatment of Cancer 30-item core quality of life (QOL) Questionnaire scores: (a). Increases in g lobal health status/QOL and function scale scores indicate increased function (improvement) (b). decreases in symptom scales indicate decreased symptoms (improvement). (DOC 104 kb)

Appendix

The following investigators contributed to this study:

Belgium—Dominique Bron, M.D., Ph.D. (Institut Jules Bordet, Brussels); Fritz Offner, M.D. (Universitair Ziekenhuis Gent, Gent); Eric Van Den Neste, M.D. (Cliniques Universitaires Saint-Luc, Brussels); USA—Arvind Aggarwal, M.D. (Dublin Hematology Oncology Care, Dublin, GA); Thomas Boyd, M.D. (Yakima Valley Memorial Hospital/North Start Lodge, Yakima, WA); Myron Czuczman, M.D. (Roswell Park Cancer Institute, Buffalo, NY); Delva Deauna-Limayo, M.D. (Nevada Cancer Institute, Las Vegas, NV); William Edenfield, M.D. (Cancer Centers of the Carolinas, Greenville, SC); Andres Forero, M.D. (University of Alabama at Birmingham, Birmingham, AL); Nathan Fowler, M.D. (The University of Texas MD Anderson Cancer Center, Houston, TX); Hassan Ghazal, M.D. (Kentucky Cancer Clinic, Hazard, KY); Robert Hermann, M.D., FACP (Northwest Georgia Oncology Center, Marietta, GA); Samuel Jacobs, M.D. (University of Pittsburgh Medical Center, Pittsburgh, PA); Stephen Kahanic, M.D. (Siouxland Hematology-Oncology Associates, Sioux City, IA); Dean Kirkel, M.D. (University Cancer Institute, Boynton Beach, FL); Dhatri Kodali, M.D. (Texas Oncology, Webster, TX); Jonathan Kolitz, M.D., FACP (Monter Cancer Center, Lake Success, NY); Shailendra Lakhanpal, M.D. (Birmingham Hematology and Oncology Associates, Birmingham, AL); Craig Okada, M.D. (Oregon Health Sciences University, Portland, OR); Dipti Patel-Donnelly, M.D. (Fairfax Northern Virginia Hematology Oncology, Fairfax, VA); Donald Quick, M.D. (Joe Arrington Cancer Research and Treatment Center, Lubbock, TX); Mansoor Saleh, M.D. (Georgia Cancer Specialists, Tucker, GA); Bradley Somer, M.D. (The West Clinic, Memphis, TN).

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Czuczman, M.S., Kahanic, S., Forero, A. et al. Results of a phase II study of bendamustine and ofatumumab in untreated indolent B cell non-Hodgkin’s lymphoma. Ann Hematol 94, 633–641 (2015). https://doi.org/10.1007/s00277-014-2269-8

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  • DOI: https://doi.org/10.1007/s00277-014-2269-8

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