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3100 Glofitamab and Epcoritamab in the Real World: A UK Multicentre Retrospective Analysis of Efficacy, Tolerability and Practical Implications

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Adult, Lymphomas, Non-Hodgkin lymphoma, Bispecific Antibody Therapy, Clinical Research, Diseases, Real-world evidence, Aggressive lymphoma, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Adverse Events, Study Population, Human
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Euan Haynes, MBBS1*, Kushani Ediriwickrema, MBBS, BSc, MRCPI2,3*, Sarah Lawless, BSc, FRCPath, MRCP4*, Kevin Joyce5*, Matthew Wells6*, Jeffrey Smith5*, Kim Linton7*, Anna Santarsieri, MBBS8*, George Follows, MA, BM, BCh, PhD, FRCP, FRCPath8*, John Willan, BMBS9*, Robert Osborn10*, Matthew R Wilson11*, Pamela McKay, MBChB (Hons), FRCP, FRCPath10*, Mahina Baloch, MBBS12*, Rory McCulloch, FRCPath, MRCP, MBBS12*, Mary Gleeson13*, David Wrench13,14*, David Foldes, MBBS15*, Edward Kanfer15*, Kyaw Zin Maw, FRCPath16*, Andrea Kuhnl17*, Matthew Ahearne18*, Mary Owen19*, Jane Norman20*, Ravindu De Silva, MBBS21*, Nimish Shah22*, Harriet Ambrose23*, Christopher P. Fox, MBChB(Hons), PhD, FRCP24, Janine Qasim25*, Graham P. Collins25, Martha Vickers26*, David Tucker27, Li Yuan Chan28*, Sunil Iyengar29, Dima el-Sharkawi29*, Rebecca Auer, MD, PhD30*, Catherine Cox31*, Hwai Jing Hiew, MD, FRCPath32*, Andrew J. Davies, MD, PhD32*, Philippa Kelsey, MBChB MRCP FRCPath33*, David John Lewis, MD34*, Abigail Martin34*, Gavin Preston, PhD, MBBS, FRCP, FRCPath35*, Dominic J. Culligan, MD, FRCP, FRCPath, BSc, MBBS35*, Angus Broom36*, William Wilson, PhD37*, Wendy Osborne, MD38,39* and William Townsend40*

1Newcastle-Upon-Tyne NHS Foundation Trust, Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
2University College London Hospitals NHS Foundation Trust, London, GBR
3University College London, CRUK and UCL Cancer Trials Centre, London, United Kingdom
4Belfast Health and Social Care Trust, Belfast City Hospital, Belfast, GBR
5Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, United Kingdom
6Clatterbridge Cancer Centre NHS Foundation Trust,, Liverpool, United Kingdom
7The Christie NHS Foundation Trust, Manchester Cancer Research Centre, and Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
8Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom
9Frimley Park Hospital, Frimley Health NHS Foundation Trust, Surrey, United Kingdom
10Beatson West of Scotland Cancer Centre, Greater Glasgow and Clyde NHS Foundation Trust, Glasgow, United Kingdom
11Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
12Gloucestershire Hospitals NHS Foundation Trust, Gloucester, United Kingdom
13Guys Hospital, Guys and St Thomas' NHS Trust, London, United Kingdom
14Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom
15Imperial College Healthcare NHS Trust, London, United Kingdom
16James Paget University Hospital NHS Foundation Trust, Norfolk, United Kingdom
17King's College Hospital NHS Foundation Trust, London, United Kingdom
18University Hospitals Leicester NHS Trust, Leicester, United Kingdom
19Leeds Teaching Hospital NHS Trust, Leeds, United Kingdom
20Manchester Royal Infirmary, Manchester, United Kingdom
21Norfolk and Norwich University Hospitals NHS Foundation Trust, Norfolk, United Kingdom
22Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom
23Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
24School of Medicine, University of Nottingham, Nottingham, United Kingdom
25Oxford University Hospitals, Oxford, United Kingdom
26Royal Cornwall Hospital NHS Trust, Cornwall, United Kingdom
27Haematology Department, Royal Cornwall Hospital, Truro, United Kingdom
28Royal Marsden NHS Foundation Trust, London, United Kingdom
29The Royal Marsden NHS Foundation Trust, London, United Kingdom
30Barts Health NHS Trust, London, United Kingdom
31St. George's University Hospitals NHS Foundation Trust, London, United Kingdom
32University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
33Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
34University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom
35Aberdeen Royal Infirmary, NHS Grampian, Aberdeen, United Kingdom
36Western General Hospital, NHS Lothian, Edinburgh, United Kingdom
37Cancer Research UK & UCL Cancer Trials Centre, University College London Cancer Institute, London, United Kingdom
38Newcastle Hospitals NHS Trust, Newcastle Upon Tyne, United Kingdom
39Newcastle University, Newcastle, United Kingdom
40University College Hospital London, London, United Kingdom

Background

Glofitamab (Glofit) and Epcoritamab (Epco), CD3:CD20 bispecific monoclonal antibodies (BsABs), have demonstrated remarkable monotherapy activity in relapsed/refractory large B-cell lymphoma with complete response rates (CRR) of 39% in their registration trials and durable remissions in many responding patients. Data from these trials indicate similar outcomes independent of prior CAR-T exposure. These data led to the licencing of both drugs internationally in 2023; in the UK access was granted in 2023 initially via compassionate access prior to full license and reimbursement. Real world data is limited and urgently needed to better understand efficacy and tolerability. To our knowledge, this is the largest real world data set of both drugs.

Aims

To provide insights into efficacy, tolerability, and practical implications of delivery of BsABs in the real world setting.

Methods

A multicentre, retrospective analysis of anonymised data from patients treated on UK compassionate/early access schemes or licensed approval.

Results

142 patients (pts.) were approved for Glofit at 26 UK centres: median age 68 years (range 25-90), 63% male and 99% performance status 0-2. Histological diagnoses included DLBCL (NOS) (61%), transformed follicular lymphoma (18%) and other NHL (20%). IPI score ≥3 in 54% (n=74), bulky disease in 23% (n=33) and a median of 3 lines of prior treatment with 15% (n=22) having received ≥4 lines. 60% (n=80) had prior CAR-T and 84% (n=117) were refractory to their most recent treatment. The majority (74%, n=86) wouldn’t have met registration trial eligibility, reasons included cytopenias (n=63), performance status (n=24), co-morbidity (n=7) and CNS involvement, prior or current (n=4).

6 pts didn’t receive Glofit due to PD prior to starting. At data cut-off, treatment was ongoing in 30 pts. A median of 3 (1-12) cycles were delivered with treatment delays in 36% (n=36). 33% (n=44) experienced cytokine release syndrome (CRS) (maximum grade 3 (4%, n=5), grade 2 (12%, n=16)) with 23 pts (17%) receiving tocilizumab. Immune effector cell-associated neurotoxicity syndrome (ICANS) was seen in 4% (n=5) (maximum grade 3 (1%, n=1), grade 2 (1%, n=1)). 22% (n=29) experienced grade ≥3 neutropenia and 45% (n=61) experienced infection during treatment. 7 pts (5%) required intensive care unit (ICU) admission, with no treatment-related deaths.

With a median follow-up of 6.1 months (IQR 2.5-9.1), complete metabolic response (CMR) was achieved in 27% (95% CI 19-36) with an overall response rate (ORR) 61% (95% CI 37-56). 6-month duration of CR (DoCR) was 86% (95% CI 53-96) with only 2/30 pts who achieved CR relapsing to date with short follow-up. Intention to treat (ITT) 6 month overall survival was 53% (95% CI 42-62) and 6 month progression free survival 44% (95% CI 34-53). Pts with prior Bendamustine (Benda) exposure (n=84) had inferior responses compared to Benda naïve pts (n=44) CRR 20% (95% CI 11-31) vs. 36% (95% CI 22-52), p=0.05, but this was restricted to those who had received Benda <6months prior to Glofit, CRR 9% (95% CI 2-21) vs. CRR 38% (95% CI 19-59), p=0.01.

Pts previously treated with CAR-T had a CRR 24% (95% CI 14-35), while CAR-T naïve patients had CRR 32% (95% CI 18-47), p=0.4. CRRs were higher in pts receiving Glofit >3 months post CAR-T, CRR 28% (95% CI 16-42) vs. 8% (95% CI 0.2-36), p=0.16.

38 pts were approved for Epco across 16 UK centres with a higher proportion of pts with ECOG ≥2 than the Glofit cohort. 1 pt progressed prior to starting treatment. 33% (n=9) experienced CRS (maximum grade 2, 10% (n=3)) and 2 pts (6%) received tocilizumab. 10% (n=3) experienced ICANS (maximum grade 3 (3% (n=1)), grade 2 (3% (n=1)) with 1 pt requiring ICU admission and no treatment-related deaths. At a median follow-up of 6.5 months (IQR 1.5-8.5), CMR was seen in 26% (95% CI 10-48) and 6-month DoCR was 100% (95% CI N/A).

Summary

In an ITT, real-world analysis of heavily pre-treated pts, BsABs achieved a CMR of 27%. CRS and ICANS occurred at relatively low rates, were mainly low-grade and ICU admission was rare. Initial data suggests inferior outcomes with Glofit in pts with prior Benda exposure, especially if within 6 months. CAR-T within 3 months was also associated with inferior outcome. These data indicate that encouraging outcomes with low toxicity can be achieved in the real world setting. Further analyses are needed to assess in which pts BsABs are an appropriate alternative to CAR-T and how best to sequence these treatments.

Disclosures: Haynes: Novartis: Honoraria. Ediriwickrema: Lymphoma Research Trust: Research Funding. Smith: AbbVie: Honoraria; AstraZeneca: Honoraria; Beigene: Honoraria; Gilead: Honoraria; MSD: Honoraria; Roche: Honoraria. Linton: Viracta: Research Funding; Celgene: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Step Pharma: Research Funding; Regeneron: Research Funding; MorphoSys: Research Funding; Nurix: Research Funding; MSD: Research Funding; AstraZeneca: Research Funding; Janssen: Research Funding; CellCentric: Research Funding; ADC Therapeutics: Research Funding; Roche: Consultancy, Research Funding; Kite/Gilead: Consultancy, Research Funding; BMS: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding, Speakers Bureau; Genmab: Consultancy, Other: Member of the Epcoritamab Global Council, Research Funding. Follows: Roche, AbbVie, Janssen, Takeda, Eli-Lilly, AstraZeneca: Consultancy, Other: Lecturing. Wilson: Kite Gilead: Honoraria, Other: travel grant, Speakers Bureau; Janssen: Honoraria, Other: travel grant, Speakers Bureau; Sobi: Honoraria, Speakers Bureau; Takeda: Honoraria, Other: travel grants, Speakers Bureau; Veriton Pharma: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Other: travel grant, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau. Gleeson: Incyte: Honoraria; Sobi: Honoraria. Kuhnl: Kite Gilead: Consultancy, Honoraria; Roche: Consultancy; Abbvie: Consultancy; Astra Zeneca: Honoraria, Other: Travel grant; BMS: Consultancy. Shah: Abbvie, Janssen, Roche, Kite-Gilead: Consultancy, Other: Speaker fees, scientific conferences; Abbvie, AstraZeneca, Roche, Jannsen, Kite Gilead: Consultancy, Honoraria. Fox: BeiGene, AbbVie: Research Funding; AbbVie, AstraZeneca, Atarabio, BMS, GenMab, Gilead/Kite, Incyte, Janssen, Lilly, Morphosys, Ono, Roche, SERB, SOBI, Takeda: Consultancy, Honoraria. Collins: Amgen: Research Funding; BMS: Research Funding; Kite: Honoraria, Speakers Bureau; Pfizer: Research Funding; Sobi: Consultancy, Honoraria; Beigene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Astra Zeneca: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau. Tucker: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria; Immunovant Corps: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Regeneron Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Iyengar: MSD: Honoraria; Kite/Gilead: Honoraria; Beigene: Honoraria; Astra Zeneca: Honoraria; Takeda: Honoraria. el-Sharkawi: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Conference/travel support; Adaptive: Honoraria; ASTEX: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Conference/travel support; Nurix: Honoraria; Roche: Honoraria, Other: Conference/travel support; SOBI: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria. Hiew: Roche: Speakers Bureau. Davies: Roche Pharma,: Other: Travel; Bristol Myers Squibb, Roche Pharma, Sobi, AstraZeneca, AbbVie,: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb, Roche Pharma, AstraZeneca, MSD, Cellcentric: Research Funding; Bristol Myers Squibb, Roche Pharma, Sobi, AstraZeneca, AbbVie, Johnson & Johnson,: Honoraria. Lewis: Janssen, Lilly, Roche, BeiGene, Kite, Astrazeneca: Consultancy, Honoraria. Preston: Abbive, Janssen-Cilag, Kite Gilead: Honoraria. Culligan: Abbvie: Honoraria; Celgene/BMS: Honoraria; Gilead: Honoraria; Jazz: Honoraria; Takeda: Honoraria. Broom: Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, conference fees, , Speakers Bureau; Kite Gilead: Consultancy. Osborne: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Kite Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Honoraria; Novartis: Honoraria; Kyowa Kirin: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Autolus: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Syneos: Membership on an entity's Board of Directors or advisory committees. Townsend: Research funding paid to my institution (UCL) by Roche: Research Funding; Roche, Abbvie, Sobi, Kite, Takeda, Janssen: Honoraria; Roche, Abbvie, Sobi, Kite, Takeda: Consultancy; Roche, Abbvie, Takeda, Sobi: Membership on an entity's Board of Directors or advisory committees, Other: Travel to international conferences from Roche.

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