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Outcomes of allogeneic hematopoietic cell transplantation after bispecific antibodies in non-Hodgkin lymphomas

Bone Marrow Transplantation volume 58, pages 1282–1285 (2023)Cite this article

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Immunotherapies have emerged as effective drugs for B-cell malignancies in the last decade. Specifically, the use of therapies redirecting T cells against such tumors has shown high efficacy in relapsed/refractory (r/r) B-cell lymphomas (BCL). Bispecific antibodies (BsAb) are manufactured fusion proteins that act as a bridge between cancer cells using the B-cell surface antigen (e.g. CD20) and T-cell surface activation antigen (e.g. CD3). The drug is over-the-counter medication and available for immediate use. Drugs like glofitamab, mosunetuzumab, epcoritamab and odronextamab have recently shown effectiveness in R/R BCL [1,2,3,4,5,6]. Of note, a small percentage of patients in these trials experienced treatment failure after anti-CD19 chimeric antigen receptor T-cell (CART) therapy, making BsAb a potentially promising salvage therapy in the post-CART setting.

Allogeneic hematopoietic cell transplant (alloHCT) is a curative option for patients with R/R BCL, and should be considered for fit patients with chemosensitive disease with a suitable donor [7, 8]. However, its efficacy is limited by non-relapse mortality (NRM) due to toxicity of conditioning regimen, graft-versus-host disease (GVHD) and infectious complications, especially in heavily pretreated patients. Despite such limitations, long-term OS in 20–50% is possible. Little is known about whether consolidation with an alloHCT should be considered in patients achieving a response with BsAb or if patients should continue treatment until progression or toxicity. For some high-risk patients, consolidation with alloHCT could be reasonably pursued; however, data reporting safety and outcomes of alloHCT after good response to BsAb are currently limited. To address this issue, we performed a monocentric, retrospective clinical study including adult patients (≥18 years old) who received alloHCT as consolidation following last-line therapy with an anti-CD20-CD3 BsAb therapy for r/r BCL. Informed consent for transplantation and data collection was obtained locally according to regulations applicable at the time of transplantation. The study was approved by the coordinating center’s ethical committee (EOM035/22), Hospital Universitari de Bellvitge, Barcelona, Spain) and was conducted in accordance with the Declaration of Helsinki. Response to the last line of therapy was defined as per Lugano criteria. Conditioning regimen intensity was determined using the consensus criteria. GVHD was diagnosed and staged using standard criteria. Cause of death was defined by Copelan’s algorithm. Statistical analysis was performed using SPSS version 19. From the 41 patients treated with anti CD20-CD3 BsAb for r/r BCL in a clinical trial setting (NCT03075696; NCT03533283; NCT03625037) at our institution, eight patients were consolidated with an alloHCT between April 2019 and June 2021 (Table 1 describes patients characteristics). Taking into account performance status and disease status, patients considered to have a high-risk disease received alloHCT consolidation after being withdrawn from clinical trials. AlloHCT was performed following institutional guidelines. Of note, no anti-infectious prophylaxis was administered during pre-alloHCT treatment. All patients received infection prophylaxis with acyclovir, posaconazol and inhaled pentamidine during the pre-engraftment period and trimetoprim-sulfametoxazol after achieving stable engraftment. Post-transplant cyclophosphamide plus tacrolimus and mycophenolate GVHD prophylaxis was used for both haploidentical and matched-unrelated donors.

Table 1 Patient characteristics.
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Acknowledgements

The authors thank the patients and the nursing and support staff at the Hematopoietic Cell Transplant and Cell Therapy Program, Institut Català d’Oncologia, Barcelona, Spain. They also thank CERCA Programme/Generalitat de Catalunya for institutional support.

Author contributors

MP, AM, CMo were responsible for the overall research questions and design of the study. MP performed the statistical analyses. MP, AM, CMo wrote the original draft. All authors reviewed and revised the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Clinical Hematology Department, Institut Català d’Oncologia-Hospitalet, Barcelona, Spain

    M. Peña, C. Montané, A. Paviglianiti, L. Hurtado, S. González, I. Carro, C. Maluquer, E. Domingo-Domenech, E. Gonzalez-Barca, A. Sureda & A. Mussetti

  2. Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain

    M. Peña, C. Montané, A. Paviglianiti, I. Carro, C. Maluquer, E. Domingo-Domenech, E. Gonzalez-Barca, A. Sureda & A. Mussetti

  3. Bellvitge Health Sciences Campus, University of Barcelona, Barcelona, Spain

    E. Gonzalez-Barca & A. Sureda

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Correspondence to A. Mussetti.

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Competing interests

AS reports honoraria from Takeda, BMS/Celgene, MSD, Janssen, Amgen, Novartis, Gilead Kite, Sanofi, Roche and Alexion. She served as a paid consultant for Takeda, BMS/Celgene, Novartis, Janssen, Gilead and Sanofi. She is part of the speaker’s bureau from Takeda. She received research support from Takeda and BMS/Celgene. AM served as a paid consultant for Takeda, BMS/Celgene, Merck and Jazz Pharma. He received research fundings from Gilead/Kyte.

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Peña, M., Montané, C., Paviglianiti, A. et al. Outcomes of allogeneic hematopoietic cell transplantation after bispecific antibodies in non-Hodgkin lymphomas. Bone Marrow Transplant 58, 1282–1285 (2023). https://doi.org/10.1038/s41409-023-02069-2

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