Session: 626. Aggressive Lymphomas: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Epidemiology, 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, Transplantation (Allogeneic and Autologous)
Methods: Retrospective study of pts intended for ASCT at Princess Margaret Cancer Centre from January 2014 to July 2024. Inclusion criteria: adults >18 years with a histological diagnosis of de novo or transformed LBCL receiving ST (anthracycline or platinum-based) intended for ASCT with a pre-ASCT PET/CT (typically performed after 3 cycles of (R)GDP or 4-6 cycles of anthracycline-based treatment for transformed disease) demonstrating PR (per RECIST criteria) with DS5 (SUVmax >3 times liver). A control group of pts with PR with DS4 was included. Outcomes included progression-free survival (PFS) (date of pre-ASCT PET to progression or death after cell infusion (stem cells or CAR-T cells)) and overall survival (OS) from pre-ASCT PET. Survival probability and effect sizes were calculated using Kaplan-Meier method and cox regression. A two-sided p-value of 0.05 was used to establish significance.
Results: We included 105 pts with PR on pre-ASCT PET (45: DS5, 60: DS4). Of the 45 pts with DS5, 36 proceeded to ASCT and 9 to CAR T. There were no differences in baseline characteristics (age, sex, diagnosis, refractory status, revised international prognostic index (rIPI), stage, bulk and persistently FDG avid sites) between the 3 groups (ASCT DS4, ASCT DS5, CAR-T DS5). Median age was 58 yrs (IQR 46-63); 34% were female. De novo diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma, transformed DLBCL and primary mediastinal B-cell lymphoma comprised 54%, 9%, 30% and 7% of cases, respectively. Primary refractory disease (<3 months), early relapse (3-12 months), late relapse (>12 months), and POD24 with transformed DLBCL were seen in 56%, 12%, 28%, and 4% of cases, respectively. At time of relapse, 70% had stage III/IV, 39% had bulky disease (>10 cm) and 32% had high risk rIPI. Pre-ASCT PET SUVmax was similar between the ASCT DS5 and CAR-T DS5 groups; 14.9 (95% CI 12-19.5) vs. 19.4 (95% CI 17.1-24.2), p=0.26. All pts who underwent CAR-T received axicabtagene ciloleucel: 6/9 received radiation bridging, 2/9 received steroid bridging and 1/9 received no bridging.
During a median follow up of 424 days (IQR 214-1249), 56 (53%) pts progressed and 44 (42%) died. The 6-month PFS for pts receiving ASCT DS4, ASCT DS5, and CAR-T DS5 was 73% (95% CI 60-84), 46% (95% CI 30-63), and 63% (95% CI 29-96), p<0.0001. Among pts with DS5, CAR-T vs. ASCT demonstrated a HR of 0.77 (95% CI 0.32-1.89), p=0.56. ΔSUVmax >66% did not discriminate outcomes better than DS in pts receiving ASCT. Of pts who progressed after ASCT when CAR-T was available, 63% (17/27) received third-line CAR-T. There was no difference in 6-month OS between the three groups; ASCT DS4 93% (95% CI 86-100), ASCT DS5 77% (95% CI 63-91) and CAR-T DS5 88% (95% CI 65-100), p=0.08.
Conclusion: Our data represent a sizable cohort of pre-ASCT PET DS5 pts. Outcomes in the CART D5 group were not significantly different compared to the ASCT DS group, which may be related to inadequate statistical power with small sample size. Poor outcomes are noted in pts with pre-ASCT PET DS5 disease regardless of therapeutic approach representing an area in need of improved treatment. The analysis will be updated and we intend multicentre collaboration, as determining potential differences between D5 groups could impact clinical practice.
Disclosures: 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. Crump: Kyte/Gilead: Honoraria; Canada's Drug Agency (CADTH): Honoraria; Epizyme/Ipsen: Research Funding; Roche: Research Funding. Prica: Kite-Gilead: Honoraria; Astra Zeneca: Honoraria; AbbVie: Honoraria. Bhella: Kite/Gilead: Consultancy, Honoraria. 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. Metser: Radialis: Consultancy. Kridel: Acerta Pharma: Research Funding; BMS: Research Funding; Abbvie: Research Funding; Roche: Research Funding; Eisai: Other: Travel expenses; AstraZeneca: Research Funding; Telix Pharmaceuticals: Current equity holder in publicly-traded company; ITM Isotope Technologies Munich SE: Current equity holder in private company.
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