Autologous transplant vs. CAR-T therapy in patients with DLBCL treated while in complete remission

Mazyar Shadman^{1

2}, Kwang W Ahn^{3

4}, Manmeet Kaur^{3

4}, Lazaros Lekakis⁵, Amer Beitinjaneh⁵, Madiha Iqbal⁶, Nausheen Ahmed⁷, Brian Hill⁸, Nasheed M Hossain⁹, Peter Riedell¹⁰, Ajay K Gopal^{1

2}, Natalie Grover¹¹, Matthew Frigault¹², Jonathan Brammer¹³, Nilanjan Ghosh¹⁴, Reid Merryman¹⁵, Aleksandr Lazaryan¹⁶, Ron Ram^{17

18}, Mark Hertzberg¹⁹, Bipin Savani²⁰, Farrukh Awan²¹, Farhad Khimani¹⁶, Sairah Ahmed^{22

23}, Vaishalee P Kenkre²⁴, Matthew Ulrickson²⁵, Nirav Shah^{3

26}, Mohamed A Kharfan-Dabaja⁶, Alex Herrera²⁷, Craig Sauter⁸, Mehdi Hamadani^{28

29}

Affiliations

¹ Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
² Division of Hematology and Medical Oncology, University of Washington, Seattle, WA, USA.
³ Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.
⁴ Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI, USA.
⁵ Division of Transplantation and Cellular Therapy, University of Miami Hospital and Clinics, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
⁶ Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA.
⁷ Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Cancer Center, Westwood, KS, USA.
⁸ Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
⁹ Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
¹⁰ Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
¹¹ Lineberger Comprehensive Cancer Center, Department of Medicine, Hematology Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
¹² Hematopoietic Cell Transplant and Cell Therapy Program, Massachusetts General Hospital, Boston, MA, USA.
¹³ Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
¹⁴ Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
¹⁵ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁶ Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
¹⁷ Bone Marrow Transplantation Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
¹⁸ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹⁹ Prince of Wales Hospital, Sydney, NSW, Australia.
²⁰ Long Term Transplant Clinic, Vanderbilt University Medical Center, Nashville, TN, USA.
²¹ Division of Hematology and Oncology, UT Southwestern, Dallas, TX, USA.
²² Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²³ Department of Stem Cell Transplantation & Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²⁴ Division of Hematology, Oncology, Palliative Care, Department of Medicine, University of Wisconsin, Madison, WI, USA.
²⁵ Banner MD Anderson Cancer Center, Gilbert, AZ, USA.
²⁶ BMT & Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
²⁷ Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
²⁸ Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA. mhamadani@mcw.edu.
²⁹ BMT & Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. mhamadani@mcw.edu.

PMID: 38977682
PMCID: PMC11231252
DOI: 10.1038/s41408-024-01084-w

Observational Study

Autologous transplant vs. CAR-T therapy in patients with DLBCL treated while in complete remission

Mazyar Shadman et al. Blood Cancer J. 2024.

. 2024 Jul 8;14(1):108.

doi: 10.1038/s41408-024-01084-w.

Authors

Affiliations

¹ Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
² Division of Hematology and Medical Oncology, University of Washington, Seattle, WA, USA.
³ Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.
⁴ Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI, USA.
⁵ Division of Transplantation and Cellular Therapy, University of Miami Hospital and Clinics, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
⁶ Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA.
⁷ Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Cancer Center, Westwood, KS, USA.
⁸ Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
⁹ Division of Hematology-Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
¹⁰ Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
¹¹ Lineberger Comprehensive Cancer Center, Department of Medicine, Hematology Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
¹² Hematopoietic Cell Transplant and Cell Therapy Program, Massachusetts General Hospital, Boston, MA, USA.
¹³ Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
¹⁴ Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
¹⁵ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁶ Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
¹⁷ Bone Marrow Transplantation Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
¹⁸ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹⁹ Prince of Wales Hospital, Sydney, NSW, Australia.
²⁰ Long Term Transplant Clinic, Vanderbilt University Medical Center, Nashville, TN, USA.
²¹ Division of Hematology and Oncology, UT Southwestern, Dallas, TX, USA.
²² Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²³ Department of Stem Cell Transplantation & Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²⁴ Division of Hematology, Oncology, Palliative Care, Department of Medicine, University of Wisconsin, Madison, WI, USA.
²⁵ Banner MD Anderson Cancer Center, Gilbert, AZ, USA.
²⁶ BMT & Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
²⁷ Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
²⁸ Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA. mhamadani@mcw.edu.
²⁹ BMT & Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. mhamadani@mcw.edu.

PMID: 38977682
PMCID: PMC11231252
DOI: 10.1038/s41408-024-01084-w

Abstract

In patients with relapsed DLBCL in complete remission (CR), autologous hematopoietic cell transplantation (auto-HCT) and CAR-T therapy are both effective, but it is unknown which modality provides superior outcomes. We compared the efficacy of auto-HCT vs. CAR-T in patients with DLBCL in a CR. A retrospective observational study comparing auto-HCT (2015-2021) vs. CAR-T (2018-2021) using the Center for International Blood & Marrow Transplant Research registry. Median follow-up was 49.7 months for the auto-HCT and 24.7 months for the CAR-T cohort. Patients ages 18 and 75 with a diagnosis of DLBCL were included if they received auto-HCT (n = 281) or commercial CAR-T (n = 79) while in a CR. Patients undergoing auto-HCT with only one prior therapy line and CAR-T patients with a previous history of auto-HCT treatment were excluded. Endpoints included Progression-free survival (PFS), relapse rate, non-relapse mortality (NRM) and overall survival (OS). In univariate analysis, treatment with auto-HCT was associated with a higher rate of 2-year PFS (66.2% vs. 47.8%; p < 0.001), a lower 2-year cumulative incidence of relapse (27.8% vs. 48% ; p < 0.001), and a superior 2-year OS (78.9% vs. 65.6%; p = 0.037). In patients with early (within 12 months) treatment failure, auto-HCT was associated with a superior 2-year PFS (70.9% vs. 48.3% ; p < 0.001), lower 2-year cumulative incidence of relapse (22.8% vs. 45.9% ; p < 0.001) and trend for higher 2-year OS (82.4% vs. 66.1% ; p = 0.076). In the multivariable analysis, treatment with auto-HCT was associated with a superior PFS (hazard ratio 1.83; p = 0.0011) and lower incidence of relapse (hazard ratio 2.18; p < 0.0001) compared to CAR-T. In patients with relapsed LBCL who achieve a CR, treatment with auto-HCT is associated with improved clinical outcomes compared to CAR-T. These data support the consideration of auto-HCT in select patients with LBCL achieving a CR in the relapsed setting.

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Conflict of interest statement

Mazyar Shadman reports Consulting, Advisory Boards, steering committees or data safety monitoring committees: Abbvie, Genentech, AstraZeneca, Janssen, Beigene, Bristol Myers Squibb, Morphosys/Incyte, Kite Pharma, Eli Lilly, Mustang Bio, Fate therapeutics, Nurix, Merck. Research Funding: Mustang Bio, Genentech, AbbVie, Beigene, AstraZeneca, Genmab, Morphosys/Incyte, Vincerx .Stock options: Koi Biotherapeutics. Employment: Bristol Myers Squibb (spouse). Peter Riedell has served as a consultant and/or advisory board member for AbbVie, Novartis, BMS, ADC Therapeutics, Kite/Gilead, Sana Biotechnology, Nektar Therapeutics, Nurix Therapeutics, Intellia Therapeutics, CVS Caremark, Genmab, BeiGene, Janssen, and Pharmacyclics. He has received honoraria from Novartis. Research support from BMS, Kite Pharma, Novartis, MorphoSys, CRISPR Therapeutics, Calibr, Xencor, Fate Therapeutics, AstraZeneca, Genentech, and Tessa Therapeutics. Ajay K. Gopal. Research Funding: Merck, I-Mab bio, IgM Bio, Takeda, Gilead, Astra-Zeneca, Agios, Janssen, BMS, SeaGen, Teva, Genmab. Consultancy/Honoraria: Incyte, Kite, Morphosys/Incyte, ADCT, Acrotech, Merck, Karyopharm, Servier, Beigene, Cellectar, Janssen, SeaGen, Epizyme, I-Mab bio, Gilead, Genentech, Lilly, Caribou, Fresenius-Kabi, Scitek. Stock Options: Compliment Corporation. Matthew J Frigault repots consulting and advisory roles for Kite/Gilead, BMS, Novartis, JnJ/Legend. Research funding from Arcellx, Kite/Gilead, Novartis, Incyte. Jonathan Brammer receives research funding from BMS, Incyte and consulting fee from DrenBio, Kymera. Reid Merryman: Advisory board: Genmab, Adaptive Biotechnologies, Bristol Myers Squibb, Abbvie, Inteillia, Epizyme.Consulting: Alphasights, DG Medicine.Institutional research funding: Merck, Bristol Myers Squibb, Genmab, Genentech/Roche. Aleksandr Lazaryan : Consultancy, honoraria, scientific advisory board: Sanofi. Ron Ram: Honoraria: Novartis, Gilead, Takeda, BMS, MSD, Sanofi. Mark Hertzberg: Advisory/honoraria for the following: Takeda, Janssen, Roche, Otsuka, Beigene, Gilead. Farrukh Awan has provided consultancy to: Genentech, Astrazeneca, Abbvie, Janssen, Pharmacyclics, Gilead sciences, Kite pharma, Celgene, Karyopharm, MEI Pharma, Verastem, Incyte, Beigene, Johnson and Johnson, Dava Oncology, BMS, Merck, Cardinal Health, ADCT therapeutics, Epizyme, Caribou Biosciences, Cellecter Bisosciences, Loxo Oncology, Adaptive Biotechnologies and received research funding from Pharmacyclics. Nirav Shah reports participation on advisory boards and/or consultancy for Kite Pharma, BMS-Juno, Miltenyi Biotec, Lilly Oncology, Epizyme, Incyte, Novartis, Seattle Genetics, Abbvie, and Galapagos. He has research funding, travel support, and honoraria from Lilly Oncology and Miltenyi Biotec. In addition, N.S. is on a scientific advisory board for Tundra Therapeutics. Mohamed A. Kharfan-Dabaja : Research/grant from Novartis, BMS and Pharmacyclics. Alex F. Herrera received research funding and consultancy from Bristol Myers Squibb, Genentech, Merck, Seattle Genetics, AstraZeneca, ADC Therapeutics. Research finding from KiTE Pharma and Gilead Sciences and consultancy from Karyopharm, Takeda, Tubulis, Regeneron, Genmab, Pfizer, Caribou Biosciences, Adicet Bio, Abbvie, Allogene Therapeutics Craig Sauter has served as a paid consultant for: Kite/a Gilead Company, Celgene/BMS, Gamida Cell, Karyopharm Therapeutics, Ono Pharmaceuticals, MorphoSys, CSL Behring, Syncopation Life Sciences, CRISPR Therapeutics and GSK. He has received research funds for clinical trials from: Juno Therapeutics, Celgene/BMS, Bristol-Myers Squibb, Precision Biosciences, Actinium Pharmaceuticals, Sanofi-Genzyme, Cargo Therapeutics, Affimed and NKARTA. Mehdi Hamadani reports research support/Funding: Takeda Pharmaceutical Company; ADC Therapeutics; Spectrum Pharmaceuticals; Astellas Pharma. Consultancy: ADC Therapeutics, Omeros, CRISPR, BMS, Kite, Abbvie, Caribou, Genmab. Speaker’s Bureau: ADC Therapeutics, AstraZeneca, BeiGene, Kite. DMC: Inc, Genentech, Myeloid Therapeutics, CRISPR. Other authors did not report a COI.

Figures

**Fig. 1. Auto-HCT vs CAR-T in patients with DLBCL in CR.**
A progression-free survival. B Cumulativeincidence of relapse. C Overall survival. D. Non-relapse Mortality.

See this image and copyright information in PMC

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Autologous transplant vs. CAR-T therapy in patients with DLBCL treated while in complete remission

Affiliations

Autologous transplant vs. CAR-T therapy in patients with DLBCL treated while in complete remission

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources