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High incidence of reversible renal toxicity of dose-intensified bendamustine-based high-dose chemotherapy in lymphoma and myeloma patients

Bone Marrow Transplantation volume 54, pages 1923–1925 (2019)Cite this article

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High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed non-Hodgkin lymphoma (NHL), improving progression-free (PFS) and overall survival (OS). Since decades, the BEAM regimen represents the gold standard for HDCT in lymphomas [1,2,3]. Similarly, high-dose melphalan is the standard HDCT for consolidation treatment in younger myeloma patients. Relapse after HDCT with ASCT remains the major cause of death in lymphoma and myeloma patients, and increasing the anti-tumor efficacy of both HDCT regimens remains an unmet clinical need. In addition, many of these conventional cytotoxic compounds notoriously suffer from re-supply problems in daily practice making substitute compounds desirable.

Based on these considerations, we evaluated the introduction of dose-intensified bendamustine into the current HDCT algorithms, either by replacing carmustine in the BEAM regimen thereby creating the alternative BeEAM conditioning strategy, or by adding the compound to high-dose melphalan (BenMel). Others and we have reported promising data on the use of BeEAM HDCT in relapsed NHL patients, with median PFS and OS rates at 2 years of 69 and 72%, respectively [4,5,6]. Whereas phase I/II studies identified a cumulative dose of 400 mg/m2 bendamustine (fractionated to 200 mg/m2 on two consecutive days) as the maximum tolerated dose, renal toxicity emerged as a significant issue [7,8,9]. Saleh et al. demonstrated in a case-control study of 102 lymphoma patients that BeEAM conditioning has a toxicity profile different from the BEAM regimen [10]. In particular, renal toxicity after BeEAM emerged as a concern. We previously reported in 39 lymphoma patients receiving BeEAM conditioning an incidence of renal toxicity of 28.2% (all grades), with 10.2% of grade 3 or 4 [6]. Finally, a French multicenter study reported an incidence of renal toxicity of 27.9% associated with BeEAM HDCT [11].

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Acknowledgements

The authors wish to thank the data management, the apheresis, the flow cytometry and the stem cell laboratory teams of the ASCT program at the University Hospital of Bern and its associated partner hospitals and collaborators for documentation of data relevant for this study.

Funding

A grant of the Swiss Cancer League (SCL #38-167 to TP) supported this work.

Author contributions

IP performed research and analyzed data; BJ, UN, TZ, DB and TE contributed vital material; VB and BMT contributed vital data; SF and RB analyzed data; TP designed research and analyzed data. All authors participated in drafting or reviewing the report, and all authors approved the submitted version.

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Authors and Affiliations

  1. Department of Medical Oncology, University Hospital and University of Bern, Bern, Switzerland

    Irene Prediletto, Sarah A. Farag, Barbara Jeker, Urban Novak & Thomas Pabst

  2. Department of Hematology and Central Hematology Laboratory, University Hospital and University of Bern, Bern, Switzerland

    Ulrike Bacher & Behrouz Mansouri Taleghani

  3. Department of Pharmacy, Inselspital, University Hospital and University of Bern, Bern, Switzerland

    Rachel Brégy

  4. Department of Oncology, Kantonsspital, Lucerne, Switzerland

    Thilo Zander

  5. Department of Oncology, Kantonsspital, Fribourg, Switzerland

    Daniel Betticher

  6. Department of Oncology, Bürgerspital, Solothurn, Switzerland

    Thomas Egger

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Correspondence to Thomas Pabst.

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Prediletto, I., Farag, S.A., Bacher, U. et al. High incidence of reversible renal toxicity of dose-intensified bendamustine-based high-dose chemotherapy in lymphoma and myeloma patients. Bone Marrow Transplant 54, 1923–1925 (2019). https://doi.org/10.1038/s41409-019-0508-2

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