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Impact of allogeneic hematopoietic cell transplantation on immune evasive mechanisms in relapsed refractory large B-cell lymphoma

Bone Marrow Transplantation volume 55, pages 2331–2334 (2020)Cite this article

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Large B-cell lymphoma (LBCL) is the most common subtype of non-Hodgkin’s lymphoma and its molecular pathogenesis has been extensively studied [1]. Recently, several distinct immune evasive mechanisms have been identified in LBCL, including downregulation of immune regulation components, overexpression of inhibitory pathway ligands, and generation of an immunosuppressive microenvironment [2]. Known implicated mechanisms include overexpression of MYC, dysfunction of tumor protein p53 (TP53), upregulation of program death 1/program death ligand 1 and 2 (PD1/PD-L1 and PD-L2) interactions, and downregulation of components of major histocompatibility complex (MHC) [3, 4]. It has been suggested that MYC acts as a central master regulator to maintain the overall immune suppressive environment [3].

Allogeneic hematopoietic cell transplantation (allo-HCT) is active in relapsed/refractory LBCL and results in a 30–40% long-term cure rate [5]. With the advent of reduced intensity/non-myeloablative (RIC/NMA) conditioning regimens, even older patients with significant comorbidities are routinely considered for allo-HCT [5, 6]. It has been postulated that the T-cell-mediated graft-versus-lymphoma effect induces durable long-term remission [7]. In this correlative analysis of 86 patients who underwent RIC/NMA allo-HCT at our institution for relapsed/refractory LBCL between 2003 and 2017, we examined the effect of allo-HCT on these immune evasive mechanisms. Standard institutional eligibility criteria, procedure, and supportive care for allo-HCT were applied. Previously reported patients who received alemtuzumab-containing conditioning were excluded [8]. All standard statistical analyses were performed in software R v3.5 (R development core team, Vienna, Austria).

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Fig. 1: Survival outcomes and the impact of immune evasive mechanisms.

References

  1. Pasqualucci L, Dalla-Favera R. Genetics of diffuse large B cell lymphoma. Blood. 2018;131:2307–19.

    Article  CAS  Google Scholar 

  2. de Charette M, Houot R. Hide or defend, the two strategies of lymphoma immune evasion: potential implications for immunotherapy. Haematologica. 2018;103:1256–68.

    Article  Google Scholar 

  3. Casey SC, Baylot V, Felsher DW. The MYC oncogene is a global regulator of the immune response. Blood. 2018;131:2007–15.

    Article  CAS  Google Scholar 

  4. Pascual M, Mena-Varas M, Robles EF, Garcia-Barching M, Pazino C, Hervas-Stubbs S, et al. PD-1/PD-L1 immune checkpoint and p53 loss facilitate tumor progression in activated B cell diffuse large B-cell lymphomas. Blood. 2019;133:2401–12.

    Article  CAS  Google Scholar 

  5. Fenske TS, Hamadani M, Cohen JB, Costa LJ, Kahl BS, Evens AM, et al. Allogeneic hematopoietic cell transplantation as curative therapy for patients with non-hodgkin lymphoma: increasingly successful application to older patients. Biol Blood Marrow Transplant. 2016;22:1543–51.

    Article  Google Scholar 

  6. Shah NN, Ahn KW, Litovich C, Fenske TS, Ahmed S, Battiwalla M, et al. Outcomes of Medicare-age eligible NHL patients receiving RIC allogeneic transplantation: a CIBMTR analysis. Blood Adv. 2018;2:933–40.

    Article  Google Scholar 

  7. Butcher B, Collins R. The graft-versus-lymphoma effect: clinical review and future opportunities. Bone Marrow Transplant. 2005;36:1–17.

    Article  CAS  Google Scholar 

  8. Sauter CS, Chou JF, Papadopoulos EB, Perales MA, Jakubowski AA, Young JW, et al. A prospective study of an alemtuzumab containing reduced-intensity allogeneic stem cell transplant program in patients with poor-risk and advanced lymphoid malignancies. Leuk Lymphoma. 2014;55:2739–47.

    Article  CAS  Google Scholar 

  9. Lin RJ, Ho C, Hilden PD, Barker JN, Giralt SA, Hamlin PA, et al. Allogeneic haematopoietic cell transplantation impacts on outcomes of mantle cell lymphoma with TP53 alterations. Br J Haematol. 2019;184:1006–10.

    CAS  PubMed  Google Scholar 

  10. Fenske TS, Ahn KW, Graff TM, DiGilio A, Bashir Q, Kamble RT, et al. Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation. Br J Haematol. 2016;174:235–48.

    Article  CAS  Google Scholar 

  11. Curran EK, Godfrey J, Kline J. Mechanisms of immune tolerance in leukemia and lymphoma. Trends Immunol. 2017;38:513–25.

    Article  CAS  Google Scholar 

  12. Zeiser R, Vago L. Mechanisms of immune escape after allogeneic hematopoietic cell transplantation. Blood. 2019;133:1290–7.

    Article  CAS  Google Scholar 

  13. Godfrey J, Tumuluru S, Bao R, Leukam M, Venkataraman G, Phillip J, et al. PD-L1 gene alterations identify a subset of diffuse large B-cell lymphoma harboring a T-cell–inflamed phenotype. Blood. 2019;133:2279–90.

    Article  CAS  Google Scholar 

  14. Herrera AF, Rodig SJ, Song JY, Kim Y, Griffin GK, Yang D, et al. Outcomes after Allogeneic stem cell transplantation in patients with double-hit and double-expressor lymphoma. Biol Blood Marrow Transplant. 2018;24:514–20.

    Article  Google Scholar 

  15. Xu-Monette ZY, Wu L, Visco C, Tai YC, Tzankov A, Liu W, et al. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study. Blood. 2012;120:3986–96.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported in part by National Institutes of Health award numbers P01 CA23766, NIH/NCI Lymphoma SPORE grant P50 CA192937, and NIH/NCI Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Editorial support in preparing the manuscript was provided by Hannah Rice, ELS.

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  1. These authors contributed equally: Richard J. Lin, Caleb Ho

Authors and Affiliations

  1. Adult BMT Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Richard J. Lin, Josel D. Ruiz, Molly A. Maloy, Gunjan L. Shah, Miguel-Angel Perales, Parastoo B. Dahi, Sergio A. Giralt, Michael Scordo & Craig S. Sauter

  2. Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Richard J. Lin, Gunjan L. Shah, Miguel-Angel Perales, Parastoo B. Dahi, Sergio A. Giralt, Michael Scordo, Heiko Schöder, Paul A. Hamlin, Ahmet Dogan & Craig S. Sauter

  3. Hematopathology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Caleb Ho, Allison M. Sigler & Ahmet Dogan

  4. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Sean M. Devlin

  5. Nuclear Medicine Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Heiko Schöder

  6. Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Paul A. Hamlin

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Correspondence to Richard J. Lin.

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Conflict of interest

CSS—consultant on advisory boards for: Juno Therapeutics, Sanofi Genzyme, Spectrum Pharmaceuticals, Novartis, Precision Biosciences, Kite, a Gilead Company and GSK. Research funds for investigator-initiated trials from: Juno Therapeutics and Sanofi Genzyme. AD—consultancy fees from Roche, Corvus Pharmaceuticals, Physicians’ Education Resource, Seattle Genetics, Peerview Institute, Oncology Specialty Group, Pharmacyclics, Celgene, Novartis, Takeda, EUSA Pharma. Research grants: National Cancer Institute and Roche. CH—honoraria from Invivoscribe, Inc. PAH—research support and consulting fees from Portola Pharmaceuticals, Inc. GLS—research funding from Janssen and Amgen. MS—consultancy and research funding: Angiocrine Bioscience, Inc; consultancy: McKinsey & Company; consultancy on advisory boards for: Omeros Corporation and Kite—A Gilead Company. PBD—advisory board of Kite (Gilead). SAG—advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, Jazz pharmaceutical, Takeda, Novartis, Kite, Spectrum Pharma; research funding from Amgen, Actinuum, Celgene, Johnson & Johnson, Miltenyi, Takeda. MAP—honoraria from Abbvie, Bellicum, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, and Takeda. He serves on DSMBs for Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune. Research support for clinical trials from Incyte, Kite (Gilead) and Miltenyi Biotec. The remaining authors have no conflict of interest.

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Lin, R.J., Ho, C., Devlin, S.M. et al. Impact of allogeneic hematopoietic cell transplantation on immune evasive mechanisms in relapsed refractory large B-cell lymphoma. Bone Marrow Transplant 55, 2331–2334 (2020). https://doi.org/10.1038/s41409-020-0942-1

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