-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.

735 Five-Year Survival Results from the Remodl-B Trial (ISRCTN 51837425) Show Improved Outcomes in Diffuse Large B-Cell Lymphoma Molecular Subgroups from the Addition of Bortezomib to R-CHOP Chemoimmunotherapy

Program: Oral and Poster Abstracts
Type: Oral
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Frontline Treatment of Large B-cell Lymphoma
Hematology Disease Topics & Pathways:
Research, clinical trials, Lymphomas, Combination therapy, Clinical Research, Diseases, Therapies, aggressive lymphoma, Lymphoid Malignancies
Monday, December 12, 2022: 11:00 AM

Andrew J Davies, BSc, BM, FRCP, PhD1*, Louise Stanton, MSc2*, Josh Caddy, BSc2*, Sharon Barrans, PhD3*, Sam Wilding, MSc, PhD4*, Geoff N Saunders, MSc2*, Christoph Mamot, M.D.5,6*, Urban Novak6,7*, Andrew K. McMillan, MD8, Paul A Fields, MD, PhD9, Graham P. Collins, MBBS, MA, MRCP, FRCPath, DPhil10, Richard Stephens11*, Francesco Cucco, PhD12*, Chulin Sha, PhD13*, Moniek Van Hoppe, MSc3*, Reuben M Tooze, PhD3*, Matthew A Care, PhD, MSc, BSc14*, Gareth Griffiths, PhD2*, Anna Schuh, MD, PhD, FRCP, FRCPath15, Ming-Qing Du, PhD12, David R Westhead, D. Phil. M.A.14*, Cathy Burton, MBBChir, MA, MD, FRCPath3* and Peter Johnson, MD, FRCP16

1CRUK Experimental Cancer Medicines Centre, University of Southampton, Southampton, United Kingdom
2Cancer Research UK Southampton Clinical Trials Unit, University of Southampton, Southampton, United Kingdom
3Haematological Malignancy Diagnostic Service, Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
4CRUK Southampton Clinical Trials Unit, University of Southampton, Southampton, United Kingdom
5Medical Oncology, Cantonal Hospital Aarau, Switzerland
6The Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland
7Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
8Department of Haematology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
9Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, Kings Health Partners, London, United Kingdom
10Department of Clinical Haematology, Oxford University Hospitals, Oxford, United Kingdom
11Patient Representative, NCRI Consumer Forum, London, United Kingdom
12Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom
13Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, China
14School of Molecular and Cellular Biology and Leeds Institute of Data Analytics, University of Leeds, Leeds, United Kingdom
15Department of Oncology, University of Oxford, Oxford, United Kingdom
16Cancer Research UK Experimental Cancer Medicines Centre UK, Southampton, United Kingdom

Introduction: The REMoDL-B trial compared R-CHOP versus R-CHOP + bortezomib (RB-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL) stratified by cell of origin (COO) determined by gene expression profile (GEP). The primary analysis of the trial at a median follow-up of 30 months found no overall difference in progression free (PFS) or overall survival (OS) by treatment arm. Retrospective analysis using a gene expression based classifier identified a molecular high grade group (MHG) with distinct molecular features. We present an update of this analysis and the trial final results for patients with lymphomas of activated B-cell (ABC), germinal-centre B-cell (GCB) or MHG type.

Methods: REMoDL-B was an open label randomised phase 3 adaptive trial with patients recruited from UK and Switzerland. Eligible patients had untreated, histologically confirmed DLBCL stage I-IV, were >18 year old, ECOG performance status≤2, and had cardiac, lung, renal, and liver function sufficient to tolerate full dose chemotherapy. Patients with sufficient material from initial biopsies for GEP were randomised between R-CHOP or RB-CHOP from cycle 2, stratified by international prognostic index (IPI) and COO. COO classification was performed in the trial with the DLBCL automatic classifier in time for randomisation and reassessed retrospectively adding in the MHG classifier. Time to event analyses were performed using the Kaplan-Meier method and cox regression modelling. REMoDL-B was coordinated by the Southampton Clinical Trials Unit and funded by a grant from Janssen-Cilag and endorsed by Cancer Research UK after independent peer review (C328/A12128).

Results: 801 of the 1,077 patients registered were identified as ABC, GCB or MHG type in the final analysis. 128 were unclassified and in 148 the diagnostic biopsy sample was insufficient. Median age was 65 (range 20-86) and 67% were stage III/IV, 48% had abnormal LDH, 29% had bulk, 17% had high IPI and 30% high intermediate IPI, 31% ABC, 59% GCB and 10% MHG. At a median follow up of 64 months in those still alive, there was no overall benefit of bortezomib on PFS or OS (5-year PFS of 64% in R-CHOP and 70% in RB-CHOP HR, 0.81 p=0.085, 5-year OS of 76% vs 79% HR, 0.86; p=0.32). Improved PFS and OS with RB-CHOP was however seen in ABC patients; 5-year PFS of 54% with R-CHOP vs 69% with RB-CHOP (Figure 1); 5-year OS of 67% in the R-CHOP arm vs 80% in the RB-CHOP arm: OS HR 0.58; (95% CI, 0.35 to 0.95) p=0.032. PFS was significantly improved in MHG patients: 5-year PFS 29% with R-CHOP vs 55% with RB-CHOP: HR 0.46 (95% CI 0.26-0.84) p=0.011 (Figure 2). 5-year OS was 48% vs 60% HR, 0.62; 95% (CI, 0.32 to 1.20) p=0.156. Outcomes by LymphGen classification will be presented. Adverse events were similar to those reported previously, with the most common grade 3 or worse being haematological toxicity, reported in 38% R-CHOP patients and 42% RB-CHOP patients.

Conclusions: Gene expression profiling can identify subtypes of DLBCL which may benefit from the addition of bortezomib to R-CHOP in initial therapy, specifically, ABC and MHG types.

Disclosures: Davies: Celgene, a Bristol Myers Squibb Company: Consultancy, Honoraria, Other: Travel grants / expenses, Research Funding; Roche: Consultancy, Honoraria, Other: Travel grants / expenses, Research Funding; Kite, a Gilead company: Consultancy, Honoraria, Research Funding; GSK: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Incyte: Consultancy; Janssen: Research Funding. Novak: Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Ideogen: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; H & O Communication: Honoraria. McMillan: Roche: Honoraria; Prosethetics: Honoraria; Takeda: Honoraria, Other: Travel funding; Amgen: Honoraria. Collins: Gilead: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: 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, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; SecuraBio: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants / expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants / expenses, Speakers Bureau. Griffiths: BionTech: Research Funding; BMS: Research Funding; Heartflow: Research Funding; Roche: Research Funding; Astex: Research Funding; Novartis: Research Funding; AstraZeneca: Research Funding; Jannsenn-Cilag: Research Funding; Celldex: Other. Schuh: AstraZeneca: Honoraria, Other: Non-educational grant; Exact Sciences: Honoraria; Janssen: Honoraria, Other: Non-educational grant; Abbvie: Honoraria, Other: Personal fees; Oxford Nanopore Technology: Other: In kind contributions; Illumina: Other: In-kind contributions; Adaptive Biotechnology: Honoraria; Roche: Honoraria, Other: Personal fees; SERENOx: Membership on an entity's Board of Directors or advisory committees, Other: Founder of; Gilead: Honoraria, Other: Personal fees. Burton: Roche: Consultancy. Johnson: Kymera: Honoraria; Kite Pharma: Honoraria; Incyte: Honoraria; Genmab: Honoraria; Celgene: Honoraria; BMS: Honoraria; Boehringer Ingelheim: Consultancy; Oncimmune: Consultancy; Janssen: Consultancy; Epizyme: Consultancy, Research Funding; MorphoSys: Honoraria; Novartis: Honoraria; Takeda: Honoraria.

OffLabel Disclosure: The drug is bortezomib, this is not licensed for use in diffuse large B-cell lymphoma.

*signifies non-member of ASH