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
Affiliations
Friederike Braulke
1 Department of Hematology and Medical Oncology, University Medical Center Goettingen, Germany; current address: Comprehensive Cancer Center, University Medical Center Goettingen, Germany
Florian Zettl
2 Department of Hematology and Oncology, Klinikum Traunstein, Germany
Marita Ziepert
3 Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Germany
Andreas Viardot
4 Department of Internal Medicine III, University Hospital Ulm, Germany
Christoph Kahl
5 Department of Hematology, Oncology and Palliative Care, Klinikum Magdeburg, Germany
8 Department of Hematology and Oncology, Charité University Hospital Berlin, Germany; current address: Medical Department Oncology, Lilly GmbH, Bad Homburg, Germany
Martin Dreyling
9 Department of Medicine III, University Hospital Ludwig Maximilians University, Munich, Germany
Alexander Bott
10 Department of Hematology and Medical Oncology, Paracelsus Medical University, Nuermberg, Germany
Ulrich Wedding
11 Department of Palliative Care, Jena University Hospital, Jena, Germany
Dietmar Reichert
12 Outpatient Center for Oncology, Westerstede, Germany
Maike de Wit
13 Klinik für Innere Medizin - Hämatologie, Onkologie und Palliativmedizin, Vivantes Klinikum Neukölln, Berlin, Germany
Frank Hartmann
14 Department of Hematology and Oncology, Klinikum Lippe, Lemgo, Germany
Viola Poeschel
15 Medicine 1 (Oncology, Hematology, Clinical Immunology, and Rheumatology), Saarland University Medical School, Homburg/Saar, Germany
Norbert Schmitz
16 Medical Department A, Hematology and Oncology, University Medicine of Muenster, Germany
Mathias Witzens-Harig
17 Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Germany
Wolfram Klapper
18 Department of Pathology, Hematopathology Section and Lymph Node Registry Kiel, University Hospital Schleswig-Holstein, Kiel, Germany
Andreas Rosenwald
19 Institute of Pathology, Comprehensive Cancer Center Mainfranken, University of Würzburg, Germany
Gerald Wulf
1 Department of Hematology and Medical Oncology, University Medical Center Goettingen, Germany; current address: Comprehensive Cancer Center, University Medical Center Goettingen, Germany
Bettina Altmann
3 Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Germany
Lorenz Trümper
1 Department of Hematology and Medical Oncology, University Medical Center Goettingen, Germany; current address: Comprehensive Cancer Center, University Medical Center Goettingen, Germany
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.
