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1695 Inferior Survival in Double Refractory Large B-Cell Lymphoma Eligible for Third-Line CD19 Chimeric Antigen T-Cell Therapy

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, B Cell lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Real-world evidence, Aggressive lymphoma, Treatment Considerations, Biological therapies, Lymphoid Malignancies
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Chathuri Abeyakoon, MBBS1, Sita D. Bhella, MD1, Katrina Hueniken2*, Rachel Aitken1*, Carmel Waldron3*, Anca Prica, MD1, Vishal Kukreti, MD, MSc4, Robert Kridel, MD, PhD1, Abi Vijenthira, MD, MS1, Christine I Chen, MHPE, MD5, Chloe Yang, MD6*, Richard Tsang, MD7*, David Hodgson, MD7*, Danielle Rodin, MD, MPH7*, Nauman Malik7*, Woodrow Wells7*, Michael Crump, MD1* and John Kuruvilla, MD, FRCPC1

1Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre - University Health Network, Toronto, ON, Canada
2Department of Biostatistics, Princess Margaret Cancer Centre - University Health Network, Toronto, ON, Canada
3Department of Hematology, St James' Hospital, Dublin 8, IRL
4Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
5Princess Margaret Cancer Centre - University Health Network, Toronto, ON, Canada
6Princess Margaret Cancer Centre, Toronto, ON, Canada
7Division of Radiation Oncology, Princess Margaret Cancer Centre - University Health Network, Toronto, ON, Canada

Background: Outcomes following CD19 chimeric antigen T-cell (CAR-T) therapy for patients (pts) with large B-cell lymphoma (LBCL) refractory (rf) to both an anthracycline and platinum-based therapy, referred to as double refractory (DR), are not well described. It is also unclear if these patients may be less likely to proceed to CAR-T infusion. We reviewed the outcomes of pts referred for CAR-T at our centre.

Methods: Retrospective review of the CAR-T database at the Princess Margaret Cancer Centre from April 2020 - December 2023. Anthracycline-refractoriness was defined as pts progressing/stable disease (PD/SD) on therapy or relapsing <3 months of completing treatment (typically R-CHOP). Platinum-refractoriness was defined as PD/SD while receiving platinum-based therapy (typically R-GDP). Inclusion criteria: adults >18 years from Ontario, Canada with LBCL referred for consideration of >3-line standard of care CD19 CAR-T therapy. Outcomes included progression free survival (PFS) defined from date of cell infusion to PD/death. Overall survival (OS) defined from date of initial CAR-T consultation to death. DR cohort outcomes were compared against non-double refractory (NDR) pts (defined as pts not relapsing <3 months or no PD/SD on anthracycline-based and no PD/SD on platinum-based treatment. Kaplan-Meier estimator was used to generate OS curves. Turnbull estimator was used to generate PFS curves.

Results: A total of 174 pts were identified that met inclusion criteria (59: DR, 115: NDR). There were no difference in baseline characteristics (median age, sex, ECOG, stage, disease bulk, presence of MYC and BCL2/BCL6 translocation, extra-nodal involvement including CNS disease) between the 2 cohorts. Median age 61-years (range 20-83), 63% male, median prior lines 2 (range 1-3) for LBCL and 29% had an intake ECOG of >2. Histologic subtypes: de novo diffuse large B-cell lymphoma (DLBCL) (67%), transformed DLBCL (28%), primary mediastinal B-cell lymphoma (5%). MYC and BCL2/BCL6 translocations were detected by FISH in 41/114 pts tested (35.9%). The majority had stage IV disease (53%) with extra-nodal involvement in 58%, a history of central nervous system (CNS) involvement in 6% and bulky disease (>7cm) in 43%. While no patients in the DR cohort had a prior autologous stem cell transplantation (ASCT), 43% of the NDR cohort had a prior ASCT. Bridging therapy (BT) was administered in 71% (n=122): radiotherapy (RT) (23%, n=39), chemotherapy (CT) (21%, n=36), RT and steroids (ST) (9%, n=16), ST only (9%, n=15), CT and ST (4%, n=7), CT, RT and ST (3%, n=5), CT and RT (2%, n=4), p=0.21. CAR-T product: axicabtagene ciloleucel 76%, tisagenlecleucel 24%.

Of all 174 pts, 36 (20.6%) were unable to proceed with the intended CAR-T infusion due to ineligibility (poor ECOG or PD) (48%), pt decline (22%), active CNS disease (12%), manufacturing failure (8%) or death (6%) [missing data 4%]. The failure rate to proceed with CAR-T infusion in the DR and NDR cohorts were 30.5% versus 15.6%, p=0.036.

Median follow-up for all pts was 17.5 months (range 14.7-21.1). In all pts the 12-month OS was 57% (95% CI 49-66.2%); DR 41.7% (95% CI 29.9-58%) versus NDR 65.2% (95% CI 55.6-76.6%), p=0.0046. In pts proceeding to CAR-T infusion, 12-month OS was 66.7% (95% CI 58-76.6); DR 57.2% (95% CI 42.9-76.4%) versus NDR 71% (95% CI 60.8-82.9%), p=0.23. In pts that proceeded to CAR-T infusion, 6-month PFS was 49.8% (95% CI 28.7-86.2%); DR 50.4% (95% CI 24.8-100%) versus NDR 51.7% (95% CI 29.2-91.8%), p=0.43. In pts that did not proceed to CAR-T infusion (DR: 18, NDR: 18) median OS was 2.56 months (95% CI 1.94-3.42); DR 1.94 months (95% CI 1.61-3.35) versus NDR 3.42 months (95% CI 2.56-NR), p=0.032. Univariable and multivariable analysis found DR status a predictor of inferior OS (adjusted p=0.034).

Conclusion: In our analysis, DR pts had inferior OS to NDR pts, driven by higher failure rates to proceed with CAR-T infusion. The OS of DR and NDR pts proceeding to CAR-T infusion appears similar but may be influenced by sample size. Identifying DR status at time of referral as a determinate of outcome would be clinically beneficial. Approaches to bridge DR pts to CAR-T therapy and assessing outcomes of DR pts (those progressing on platinum-based BT) in second line CAR-T therapy need to be prospectively investigated.

Disclosures: Bhella: Kite/Gilead: Consultancy, Honoraria. Prica: AbbVie: Honoraria; Kite-Gilead: Honoraria; Astra Zeneca: Honoraria. Kridel: Abbvie: Research Funding; ITM Isotope Technologies Munich SE: Current equity holder in private company; BMS: Research Funding; Acerta Pharma: Research Funding; Telix Pharmaceuticals: Current equity holder in publicly-traded company; Eisai: Other: Travel expenses; Roche: Research Funding; AstraZeneca: Research Funding. Chen: Eli Lilly and Company: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astrazeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forus Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rodin: Need Inc: Consultancy, Current holder of stock options in a privately-held company. Crump: Canada's Drug Agency (CADTH): Honoraria; Kyte/Gilead: Honoraria; Epizyme/Ipsen: Research Funding; Roche: Research Funding. Kuruvilla: DSMB Karyopharm: Other; F. Hoffmann-La Roche Ltd, AstraZeneca, Merck, Novartis: Research Funding; AbbVie, Amgen, AstraZeneca, BMS, Genmab, Gilead, Incyte, Janssen, Merck, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, Seattle Genetics: Honoraria; AbbVie, BMS, Gilead, Merck, F. Hoffmann-La Roche Ltd, Seattle Genetics: Consultancy.

*signifies non-member of ASH