Glofitamab in refractory or relapsed diffuse large B cell lymphoma after failing CAR-T cell therapy: a phase 2 LYSA study

Guillaume Cartron^{1

2}, Roch Houot^{3

4}, Yassine Al Tabaa⁵, Fabien Le Bras⁶, Loïc Ysebaert^{7

8}, Sylvain Choquet⁹, Fabrice Jardin^{10

11}, Jacques-Olivier Bay¹², François-Xavier Gros¹³, Franck Morschhauser^{14

15}, Olivier Casasnovas^{16

17}, Thomas Gastinne¹⁸, Catherine Thieblemont^{19

20}, Magalie Joris²¹, Laure Ricard²², Caroline Regny²³, Laurianne Drieu La Rochelle²⁴, Pierre Feugier^{25

26}, Ambroise Marcais²⁷, Samuel Griolet²⁸, Karin Tarte²⁹, Camille Laurent^{30

8}, Pierre Sesques³¹

Affiliations

¹ Department of Hematology, University Hospital of Montpellier, Montpellier, France. g-cartron@chu-montpellier.fr.
² UMR CNRS 5535, Montpellier, France. g-cartron@chu-montpellier.fr.
³ Department of Hematology, University Hospital of Rennes, Rennes, France.
⁴ UMR U1236, INSERM, University of Rennes, Rennes, France.
⁵ Scintidoc Nuclear Medicine Center, Clinique Clémentville, Montpellier, France.
⁶ Department of Hematology, Lymphoma Malignancies Unit, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France.
⁷ Department of Hematology, Cancer University Institute of Toulouse Oncopole, Toulouse, France.
⁸ Centre de Recherches en Cancérologie de Toulouse, INSERM U1037, Toulouse, France.
⁹ Department of Hematology, La Pitié Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
¹⁰ Department of Hematology, U1245, Henri Becquerel Institute, Rouen, France.
¹¹ INSERM U1245, Rouen, France.
¹² Department of Adults Cell Therapy and Clinical Hematology, University Hospital Clermont-Ferrand, Clermont-Ferrand, France.
¹³ Department of Clinical Hematology and Cell Therapy, University Hospital of Bordeaux, Bordeaux, France.
¹⁴ Department of Hematology, University Hospital of Lille, Lille, France.
¹⁵ ULR 7365 GRITA, Lille, France.
¹⁶ Department of Hematology, University Hospital Dijon Bourgogne, Dijon, France.
¹⁷ INSERM U1231, Dijon, France.
¹⁸ Department of Hematology, University Hospital, Nantes, France.
¹⁹ Department of Onco-Hematology, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
²⁰ University of Paris Cité, Paris, France.
²¹ Department of Hematology, University Hospital of Amiens, Amiens, France.
²² Department of Hematology, Saint Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
²³ Department of Hematology, University Hospital of Grenoble, Grenoble, France.
²⁴ Department of Hematology, University Hospital of Tours, Tours, France.
²⁵ Department of Hematology, University Hospital of Nancy, Nancy, France.
²⁶ INSERM 1256, Nancy, France.
²⁷ Department of Hematology, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
²⁸ Department of Biostatistics, LYSARC, Lyon-Sud Hospital, Pierre-Bénite, France.
²⁹ UMR1236, SITI Laboratory, University Hospital, INSERM, EFS, Rennes, France.
³⁰ Department of Pathology, Cancer University Institute of Toulouse Oncopole, Toulouse, France.
³¹ Department of Hematology, University Hospital of Lyon, Lyon, France.

PMID: 40181090
DOI: 10.1038/s43018-025-00941-2

Clinical Trial

Glofitamab in refractory or relapsed diffuse large B cell lymphoma after failing CAR-T cell therapy: a phase 2 LYSA study

Guillaume Cartron et al. Nat Cancer. 2025 Jul.

. 2025 Jul;6(7):1173-1183.

doi: 10.1038/s43018-025-00941-2. Epub 2025 Apr 3.

Authors

Affiliations

¹ Department of Hematology, University Hospital of Montpellier, Montpellier, France. g-cartron@chu-montpellier.fr.
² UMR CNRS 5535, Montpellier, France. g-cartron@chu-montpellier.fr.
³ Department of Hematology, University Hospital of Rennes, Rennes, France.
⁴ UMR U1236, INSERM, University of Rennes, Rennes, France.
⁵ Scintidoc Nuclear Medicine Center, Clinique Clémentville, Montpellier, France.
⁶ Department of Hematology, Lymphoma Malignancies Unit, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France.
⁷ Department of Hematology, Cancer University Institute of Toulouse Oncopole, Toulouse, France.
⁸ Centre de Recherches en Cancérologie de Toulouse, INSERM U1037, Toulouse, France.
⁹ Department of Hematology, La Pitié Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
¹⁰ Department of Hematology, U1245, Henri Becquerel Institute, Rouen, France.
¹¹ INSERM U1245, Rouen, France.
¹² Department of Adults Cell Therapy and Clinical Hematology, University Hospital Clermont-Ferrand, Clermont-Ferrand, France.
¹³ Department of Clinical Hematology and Cell Therapy, University Hospital of Bordeaux, Bordeaux, France.
¹⁴ Department of Hematology, University Hospital of Lille, Lille, France.
¹⁵ ULR 7365 GRITA, Lille, France.
¹⁶ Department of Hematology, University Hospital Dijon Bourgogne, Dijon, France.
¹⁷ INSERM U1231, Dijon, France.
¹⁸ Department of Hematology, University Hospital, Nantes, France.
¹⁹ Department of Onco-Hematology, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
²⁰ University of Paris Cité, Paris, France.
²¹ Department of Hematology, University Hospital of Amiens, Amiens, France.
²² Department of Hematology, Saint Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
²³ Department of Hematology, University Hospital of Grenoble, Grenoble, France.
²⁴ Department of Hematology, University Hospital of Tours, Tours, France.
²⁵ Department of Hematology, University Hospital of Nancy, Nancy, France.
²⁶ INSERM 1256, Nancy, France.
²⁷ Department of Hematology, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
²⁸ Department of Biostatistics, LYSARC, Lyon-Sud Hospital, Pierre-Bénite, France.
²⁹ UMR1236, SITI Laboratory, University Hospital, INSERM, EFS, Rennes, France.
³⁰ Department of Pathology, Cancer University Institute of Toulouse Oncopole, Toulouse, France.
³¹ Department of Hematology, University Hospital of Lyon, Lyon, France.

PMID: 40181090
DOI: 10.1038/s43018-025-00941-2

Abstract

Persons with diffuse large B cell lymphoma (DLBCL) refractory or in first progression/relapsed (R/R) after chimeric antigen receptor T (CAR-T) cell therapy exhibit dramatic outcomes. We enrolled such persons in a phase 2 single-arm, nonblinded trial ( NCT04703686 ) to evaluate the efficacy and safety of glofitamab, a CD20-CD3 T cell-engaging bispecific antibody, using a short ramp-up regimen to reach full dose within 1 week. A total of 46 participants received at least one glofitamab infusion following obinutuzumab (anti-CD20 monoclonal antibody) pretreatment. The primary endpoint was overall survival (OS). Secondary endpoints included independent-assessed best overall metabolic response rate (OMRR) and complete metabolic response rate (CMRR), progression-free survival (PFS), duration of response, safety and tolerability and health-related quality of life. After a median follow-up of 15.3 months (95% confidence interval (CI), 10.1-17.7), the primary endpoint was met, achieving a median OS of 14.7 months (90% CI, 8.8-not reached). The best OMRR was 76.1%. The best CMRR was 45.7%. The median PFS was 3.8 months (95% CI, 2.4-19.6). Despite the shortened setup dosing, no excess cytokine release syndrome or neurotoxicity events were observed (grade ≥ 3, 0% for both). In conclusion, glofitamab improved OS in participants with R/R DLBCL after CAR-T cell therapy, with a favorable safety profile.

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Conflict of interest statement

Competing interests: G.C. has received honoraria and advisory/consultancy fees from Roche, Bristol-Myers Squibb, BeiGene, Novartis, Kite/Gilead, Takeda, AstraZeneca, AbbVie, Janssen, Onward Therapeutics and Mabqi. R.H. has received honoraria from Kite/Gilead, Novartis, Incyte, Janssen, MSD, Takeda and Roche and is a member on the board of directors or advisory committee of Kite/Gilead, Novartis, Bristol-Myers Squibb/Celgene, ADC Therapeutics, Incyte and Miltenyi. L.Y. has received honoraria and advisory/consultancy fees from AbbVie, AstraZeneca, BeiGene, Bristol-Myers Squibb/Celgene, Gilead/Kite, Janssen and Roche. S.C. has received honoraria and advisory/consultancy fees from AbbVie, AstraZeneca, Atara, BeiGene, Gilead/Kite, Janssen, Novartis, Pierre Fabre and Takeda. F.J. has received honoraria and advisory/consultancy fees from Roche, Bristol-Myers Squibb, Novartis, Kite/Gilead, Takeda, AbbVie and Janssen. F-X.G. has received honoraria and advisory/consultancy fees from Bristol-Myers Squibb, Novartis, Kite/Gilead, AstraZeneca, Janssen and Miltenyi. F.M. has received consultancy fees from AbbVie, Bristol-Myers Squibb, Gilead, Novartis and Roche, serves as an advisor for AbbVie, Gilead and Roche and has received honoraria from Chugai and Kaleda for scientific lectures. O.C. has received honoraria and advisory/consultancy fees from Roche, Takeda, Gilead/Kite, Bristol-Myers Squib, MSD, AbbVie, BeiGene and ADC therapeutics. T.G. has received travel and accommodation expenses from Roche. C.T. has received honoraria and advisory/consultancy fees from Roche, Bristol-Myers Squibb, Novartis, Kite/Gilead, Takeda, AbbVie and Janssen. L.D.L.R. has received honoraria and advisory/consultancy fees from Gilead/Kite, Novartis, Bristol-Myers Squibb, Janssen and Takeda. P.F. has received honoraria and advisory/consultancy fees from BeiGene, Kite/Gilead, AstraZeneca, AbbVie and Janssen. S.G. is an employee of LYSARC. P.S. has received honoraria and advisory/consultancy fees from Janssen, Roche, Bristol-Myers Squibb, AbbVie, AstraZeneca, Chugai, Novartis and Kite/Gilead. Y.A.T., M.J., C.L., F.L.B., A.M., J-O.B., C.R., L.R. and K.T. declare no competing interests.

References

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Glofitamab in refractory or relapsed diffuse large B cell lymphoma after failing CAR-T cell therapy: a phase 2 LYSA study

Affiliations

Glofitamab in refractory or relapsed diffuse large B cell lymphoma after failing CAR-T cell therapy: a phase 2 LYSA study

Authors

Affiliations

Abstract

Conflict of interest statement

References

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Miscellaneous