-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

441 Relapse Is Uncommon in Patients with Large B-Cell Lymphoma Who Are in Complete Remission at the End of Fixed-Course Glofitamab TreatmentClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Immune Based and Targeted Therapies in Relapsed/Refractory Large B-Cell Lymphoma
Hematology Disease Topics & Pathways:
Biological therapies, non-Hodgkin lymphoma, Lymphomas, Bispecific Antibody Therapy, B Cell lymphoma, Diseases, aggressive lymphoma, Therapies, Lymphoid Malignancies
Sunday, December 11, 2022: 10:00 AM

Martin Hutchings, MD, PhD1*, Carmelo Carlo-Stella, MD, PhD2, Franck Morschhauser, MD, PhD3*, Emmanuel Bachy, MD, PhD4*, Paolo Corradini, MD5, Gloria Iacoboni, MD6*, Cyrus Khan7*, Krish Patel8*, Mark Hertzberg, MBBS9*, Lorenzo Falchi, MD10, Nancy L. Bartlett, MD11, Joshua Brody, MD12, Linda Lundberg13*, Yuying Xie14*, Estefania Mulvihill13*, Pauline Baumlin13*, James Relf15*, Emily Piccione16*, Kathryn Humphrey15* and Michael Dickinson, MD17

1Rigshospitalet, Copenhagen, Denmark
2Humanitas University and IRCCS Humanitas Research Hospital, Milan, Italy
3Hematology Department, Lille University Hospital, Lille, France
4Department of Hematology, Hospices Civils de Lyon, Lyon Sud University Hospital, Pierre Benite, France
5Università degli Studi di Milano and Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCSS) Istituto Nazionale dei Tumori, Milan, Italy
6Vall d’Hebron University Hospital, Barcelona, Spain
7Allegheny Health Network, Pittsburgh, PA
8Swedish Cancer Institute, Seattle, WA
9Prince of Wales Hospital and University of New South Wales, Sydney, NSW, Australia
10Memorial Sloan Kettering Cancer Center, New York, NY
11Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
12Tisch Cancer Institute, New York, NY
13F. Hoffmann-La Roche Ltd, Basel, Switzerland
14F. Hoffmann-La Roche Ltd, Mississauga, Canada
15Roche Products Ltd, Welwyn Garden City, United Kingdom
16Genentech, Inc., South San Francisco, CA
17Peter MacCallum Cancer Centre, Royal Melbourne Hospital and The University of Melbourne, Melbourne, Australia

Background: Glofitamab, a CD20xCD3 T-cell-engaging bispecific monoclonal antibody with a novel 2:1 (CD20:CD3) configuration, redirects T cells to eliminate normal and malignant B cells. Glofitamab is an off-the-shelf treatment, administered intravenously (IV) for a fixed duration of 12 cycles. In pivotal expansion cohorts of an ongoing Phase I/II study (NP30179; NCT03075696), glofitamab has demonstrated a manageable safety profile and induced frequent and durable complete responses (CRs) in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL; Dickinson et al. ASCO 2022). Here, we present data for the duration of CR from end-of-treatment (EOT) in patients with R/R LBCL enrolled in the dose escalation and expansion phases of this study.

Methods: Patients with R/R LBCL with ≥1 prior line of therapy (diffuse large B-cell lymphoma not otherwise specified [DLBCL NOS], high-grade B-cell lymphoma [HGBCL], primary mediastinal large B-cell lymphoma [PMBCL] or transformed follicular lymphoma [trFL]) were enrolled. Patients received 1000mg obinutuzumab pre-treatment 7 days prior to first dose of glofitamab, followed by IV glofitamab for up to 12 cycles (8.4 months). Glofitamab was given at a fixed dose (0.6–25mg) or with step-up dosing (target dose: 16mg or 30mg) every three weeks. Responses were assessed using Lugano 2014 criteria (Cheson et al. J Clin Oncol 2014).

Results: As of March 14, 2022, 61/214 (29%) patients with R/R LBCL who had received glofitamab at a dose of ≥0.6mg, including suboptimal doses, were in CR by investigator assessment at EOT by intent-to-treat analysis (DLBCL, n=41; trFL, n=18; HGBCL, n=1; PMBCL, n=1). Median age was 67 years (range: 22–85), and 51% were female. The median number of prior lines of therapy was 3 (range: 2–9), and the majority of patients (61%) had received ≥3 prior therapies. Overall, 43% of patients were refractory to their initial therapy, and 74% were refractory to their most recent regimen.

The median duration of CR follow-up was 18.1 months (95% confidence interval [CI]: 14.8–20.7). Fifty-three patients had reached 6 months follow-up post-EOT; the majority of patients with a CR at EOT (45/61; 74%) remained in CR, 1/61 (2%) had experienced progressive disease (PD), and 8/61 (13%) remained in follow-up but had not yet reached 6 months. At 12 months post-EOT, 34/61 (56%) patients remained in CR, 1/61 (2%) had experienced PD, and 17/61 (28%) remained in follow-up but had not yet reached 12 months. One patient experienced PD between 12 and 18 months post-EOT (Figure). Forty-six percent of patients had been in follow-up long enough to reach their 18-month post-EOT visit, and 20% of patients had reached their 42-month post-EOT visit. The median duration of CR had not been reached. Of the three patients who experienced PD after having a CR at EOT, one patient had initiated re-treatment at the time of the analysis and achieved a second CR. Five patients discontinued the study (two received an allogeneic transplant, two due to physician decision, one lost to follow-up). Five patients died (one due to secondary malignancy, two due to PD, two for unknown/other reasons).

Conclusions: Most patients with LBCL who achieved a CR at EOT experienced durable responses in the absence of continued treatment. Only 1 of 44 patients who reached 12 months follow-up post-EOT experienced progression. Longer follow-up is needed to further confirm the off-treatment durability of glofitamab-induced CRs in patients with R/R LBCL beyond the 12-month timepoint. It is particularly encouraging that off-treatment progression was rarely observed in this heavily pre-treated, largely treatment-refractory, LBCL patient population.

Disclosures: Hutchings: Celgene: Consultancy, Research Funding; Novartis: Research Funding; Genmab: Consultancy, Research Funding; Genentech: Research Funding; Janssen: Consultancy, Research Funding; Incyte: Research Funding; Roche: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; AbbVie, Celgene, Genmab, Janssen, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene, Genentech, Genmab, Incyte, Janssen, Novartis, Roche, Takeda: Research Funding; AbbVie: Consultancy. Carlo-Stella: Bristol Myers Squibb: Honoraria; ADC Therapeutics: Honoraria, Other: Consultancy/Advisory, Research Funding; Sanofi: Other: Consultancy/Advisory, Research Funding; Merck Sharp & Dohme: Honoraria; Janssen Oncology: Honoraria; Roche: Other: Consultancy/Advisory, Research Funding; Celgene/Bristol Myers Squibb: Other: Consultancy/Advisory; Takeda: Honoraria; Novartis: Honoraria; Incyte: Honoraria; AstraZeneca: Honoraria; Karyopharm Therapeutics: Other: Consultancy/Advisory; Scenic Biotech: Other: Consultancy/Advisory. Morschhauser: AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Allogene therapeutics: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Membership on an entity's Board of Directors or advisory committees; Janssen: Speakers Bureau; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genmab: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bachy: Kite, Gilead, Novartis, Roche, Incyte, Miltenyi Biotech, Takeda, Sanofi: Honoraria; Roche, Gilead, ADC Therapeutics, Takeda, Novartis, Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen, BMS: Research Funding; Hospices Civils de Lyon: Current Employment. Corradini: takeda: Honoraria; janssen: Honoraria; incyte: Honoraria; gilead: Honoraria; celgene: Honoraria; amgen: Honoraria; abbvie: Honoraria. Iacoboni: NOVARTIS, KITE/GILEAD, BMS/CELGENE: Consultancy; NOVARTIS, KITE/GILEAD, BMS/CELGENE, ASTRAZENECA, ROCHE, ABBVIE, JANSSEN, MILTENYI: Honoraria. Khan: Allegheny Health Network, Pittsburgh, PA: Current Employment; Acceleron, AstraZeneca, Beigene, Sanofi: Consultancy; Genentech, Beigene: Research Funding; BMS, AstraZeneca, Beigene, Sanofi, Incyte, Amgen, Genentech, Epizyme, Karyopharm, SeaGen, Pharmacyclics, Janssen: Honoraria, Speakers Bureau. Patel: AstraZenca, BMS, Celgene, Roche/Gen, Kite, Pharmacyclics/Janssen, TG: Speakers Bureau; Adaptive Biotechnologies, AptevoTherapeutics, AstraZeneca, BMS, Celgene, CRISPR, Curis, Epizyme, Fate Therapeutics, Roche/Gen, Kite, MEI, Nurix, Pharmacyclics/Janssen, Sunesis Pharmaceuticals, Trillium Therapeutics/Pfizer, Velos Bio, Xencor: Research Funding; Abbvie, ADC Therapeutics, AstraZeneca, Beigene, BMS, Caribou Biosciences, Celgene, Epizyme, Roche/Gen, Kite, MEI, Morphosys, Pharmacyclics/Janssen, TG, Trillium Therapeutics/Pfizer, Xencor: Consultancy. Hertzberg: Takeda: Membership on an entity's Board of Directors or advisory committees; Otsuka: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Roche, Takeda, Otsuka, Beigene, Gilead, Janssen, Novartis, Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Falchi: ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Seagen: Membership on an entity's Board of Directors or advisory committees. Bartlett: Autolus, Bristol-Meyers Squibb, Celgene, Forty Seven, Janssen, Kite Pharma, Merck, Millennium, Pharmacyclics: Research Funding; Washington University School of Medicine: Current Employment; ADC Therapeutics, Roche/Genentech, Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Brody: Genentech: Research Funding; Gilead/Kite: Research Funding; Merck: Research Funding; SeaGen, Roche, Genentech, Merck, ADC Therapeutics, Epizyme, Gilead, Kite, Astrazeneca: Research Funding; BMS: Research Funding; Seagen: Consultancy; ADC Therapeutics: Consultancy; Epizyme: Consultancy. Lundberg: F-Hoffmann La Roche: Current Employment, Current equity holder in private company, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months, Patents & Royalties. Xie: Roche: Current Employment. Mulvihill: Hoffmann-La Roche: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Baumlin: Hoffmann La Roche: Current Employment. Relf: Roche, F-Star Therapeutics: Current equity holder in publicly-traded company; Roche, F-Star Therapeutics and Harpoon Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months; Roche Products Limited: Current Employment. Piccione: F. Hoffman-LaRoche Ltd: Current equity holder in publicly-traded company; Genentech, Inc: Current Employment. Humphrey: Roche Products Ltd: Current Employment; Roche: Current equity holder in private company, Current holder of stock options in a privately-held company. Dickinson: Roche, BMS, Novartis, Kite, Gilead, NKARTA, AdiCet Bio, Interius, Janssen, MSD: Consultancy; Roche, BMS, Novartis, Kite, Gilead, NKARTA, AdiCet Bio, Interius, Janssen, MSD, Amgen: Honoraria; Roche, Novartis, Kite, Gilead, MSD, Takeda, Celgene: Research Funding.

OffLabel Disclosure: Glofitamab is a full-length, humanized immunoglobulin G1 bispecific monoclonal antibody with a 2:1 (CD20:CD3) configuration that facilitates bivalent binding to CD20 on B cells, and monovalent binding to CD3 on T cells. Glofitamab redirects T cells to eliminate normal and malignant B cells. Glofitamab is an investigational agent. Obinutuzumab (Gazyva) is a CD20-directed cytolytic antibody indicated: in combination with chlorambucil, for the treatment of patients (pts) with previously untreated CLL; in combination with bendamustine followed by obinutuzumab monotherapy, for the treatment of pts with FL who relapsed after, or are refractory to, a rituximab-containing regimen; in combination with chemo followed by obinutuzumab monotherapy in pts achieving at least a PR, for the treatment of adult pts with previously untreated stage II bulky, III or IV FL.

*signifies non-member of ASH