First-line Treatment With Bendamustine and Rituximab for Old and Frail Patients With Aggressive Lymphoma: Results of the B-R-ENDA Trial

Friederike Braulke; Florian Zettl; Marita Ziepert; Andreas Viardot; Christoph Kahl; Gabriele Prange-Krex; Agnieszka Korfel; Martin Dreyling; Alexander Bott; Ulrich Wedding; Dietmar Reichert; Maike de Wit; Frank Hartmann; Viola Poeschel; Norbert Schmitz; Mathias Witzens-Harig; Wolfram Klapper; Andreas Rosenwald; Gerald Wulf; Bettina Altmann; Lorenz Trümper

doi:10.1097/HS9.0000000000000808

First-line Treatment With Bendamustine and Rituximab for Old and Frail Patients With Aggressive Lymphoma: Results of the B-R-ENDA Trial

Hemasphere. 2022 Dec 1;6(12):e808. doi: 10.1097/HS9.0000000000000808. eCollection 2022 Dec.

Authors

Friederike Braulke¹, Florian Zettl², Marita Ziepert³, Andreas Viardot⁴, Christoph Kahl^{5

6}, Gabriele Prange-Krex⁷, Agnieszka Korfel⁸, Martin Dreyling⁹, Alexander Bott¹⁰, Ulrich Wedding¹¹, Dietmar Reichert¹², Maike de Wit¹³, Frank Hartmann¹⁴, Viola Poeschel¹⁵, Norbert Schmitz¹⁶, Mathias Witzens-Harig¹⁷, Wolfram Klapper¹⁸, Andreas Rosenwald¹⁹, Gerald Wulf¹, Bettina Altmann³, Lorenz Trümper¹

Affiliations

¹ Department of Hematology and Medical Oncology, University Medical Center Goettingen, Germany; current address: Comprehensive Cancer Center, University Medical Center Goettingen, Germany.
² Department of Hematology and Oncology, Klinikum Traunstein, Germany.
³ Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Germany.
⁴ Department of Internal Medicine III, University Hospital Ulm, Germany.
⁵ Department of Hematology, Oncology and Palliative Care, Klinikum Magdeburg, Germany.
⁶ Department Internal Medicine, Clinic III - Hematology, Oncology and Palliative Care, Rostock University Medical Center, Rostock, Germany.
⁷ Onkologische Gemeinschaftspraxis, Dresden, Germany.
⁸ Department of Hematology and Oncology, Charité University Hospital Berlin, Germany; current address: Medical Department Oncology, Lilly GmbH, Bad Homburg, Germany.
⁹ Department of Medicine III, University Hospital Ludwig Maximilians University, Munich, Germany.
¹⁰ Department of Hematology and Medical Oncology, Paracelsus Medical University, Nuermberg, Germany.
¹¹ Department of Palliative Care, Jena University Hospital, Jena, Germany.
¹² Outpatient Center for Oncology, Westerstede, Germany.
¹³ Klinik für Innere Medizin - Hämatologie, Onkologie und Palliativmedizin, Vivantes Klinikum Neukölln, Berlin, Germany.
¹⁴ Department of Hematology and Oncology, Klinikum Lippe, Lemgo, Germany.
¹⁵ Medicine 1 (Oncology, Hematology, Clinical Immunology, and Rheumatology), Saarland University Medical School, Homburg/Saar, Germany.
¹⁶ Medical Department A, Hematology and Oncology, University Medicine of Muenster, Germany.
¹⁷ Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Germany.
¹⁸ Department of Pathology, Hematopathology Section and Lymph Node Registry Kiel, University Hospital Schleswig-Holstein, Kiel, Germany.
¹⁹ Institute of Pathology, Comprehensive Cancer Center Mainfranken, University of Würzburg, Germany.

Abstract

The incidence of aggressive B-cell lymphomas increases with age, but for elderly or frail patients not eligible for doxorubicin-containing treatment standard therapy remains to be defined. In this prospective, multicenter, phase-2 B-R-ENDA trial, we investigated the feasibility, toxicity, and efficacy of 8 cycles rituximab combined with 6 cycles bendamustine (BR) in elderly or frail aggressive B-cell lymphoma patients: 39 patients aged >80 years and 29 patients aged 61-80 years with elevated Cumulative Illness Rating Scalescore >6 were included. Progression-free survival (PFS) and overall survival (OS) at 2 years were 45% (95% confidence interval [CI], 28%-61%) and 46% (28%-63%) for the patients age >80, as well 32% (13%-51%) and 37% (17%-57%) for frail patients age 64-80, respectively. In a preplanned retrospective analysis, we found no significant differences in PFS and OS comparing the outcome of the 39 patients age >80 years with 40 patients aged 76-80 years treated with 6xR-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) and 2 x rituximab in the RICOVER-60 trial (DSHNHL 1999-1, NCT00052936, EU-20243), yet we detected lower rates of infections and treatment-related deaths in the BR-treated patients. We demonstrate that older and frail patients with aggressive B-cell lymphoma who are not able to receive standard CHOP-based therapy can benefit from anthracycline-free therapy as a feasible and effective therapeutic option.