Session: 703. Adoptive Immunotherapy: Mechanisms and New Approaches: Poster III
Hematology Disease Topics & Pathways:
Biological, Diseases, Therapies, CAR-Ts, DLBCL, B-Cell Lymphoma, immunotherapy, Lymphoid Malignancies, transplantation
METHODS: Eligible were all patients referred to our institution with relapsed/refractory (R/R) DLBCL and a tumor board decision recommending treatment with CAR-T cells between 07/2018 and 02/2020 and those recommending allogeneic donor search between 2004 and 2019. Patients with DLBCL transformed from CLL were excluded. EASIX was evaluated retrospectively using uni- and multivariable analyses (with regards to age, gender and number of failed therapy lines) and mortality using Cox regression analyses.
RESULTS: 41 patients intended for CAR-T cells and 60 patients intended for alloHCT were included. In both cohorts nearly all patients had active disease at indication. Cohorts were comparable for sex, time from diagnosis, ZUMA1 eligibility, and PS, but CAR-T patients tended to be older (median 56 vs 51 years, p=0.093), and had more often primary refractory and bulky disease (p=0.004 and p=0.04, respectively). Median EASIX score across both cohorts was 1.50 (0.27-70.5), with significantly higher scores in the CART group both at indication (EASIX-ind; median 1.79 and 1.22 for CAR-T and alloHCT, respectively, p=0.031) and at conditioning for CI (EASIX-pre, median 2.24 vs 1.26, p=0.005). Median OS from indication was 475d for the CAR-T cohort vs 285d for the alloHCT cohort (p=0.88). On multivariate analysis, EASIX-ind was significantly associated with adverse OS if alloHCT was intended (HR per 2fold increase 1.43, 95%CI 1.08-1.90, p=0.013), but not if CAR-T was intended (HR per 2fold increase 1.16, 95%CI 0.88-1.53, p=0.3). After CI, 12-month estimates for NRM, relapse incidence, PFS, and OS for CAR-T vs alloHCT were 3% vs 21% (p=0.04), 59% vs 44% (p=0.12), 39% vs 33% (p=0.97), and 68% vs 54% (p=0.32). EASIX-pre predicted overall survival (OS) in both CAR-T (HR per 2fold increase 2.11, 95%CI 1.21-3.7, p=0.009) and alloHCT (HR per 2fold increase 3.69, 95%CI 1.54-8.31, p=0.003) cohorts. In the alloHCT group, the EASIX effect was largely driven by higher NRM risk with increasing EASIX-pre, while in the CAR-T group poorer OS with increasing EASIX-pre was largely relapse-related.
CONCLUSIONS: In patients undergoing CI for r/r LBCL, EASIX measured prior to conditioning can predict mortality after both CAR-T and alloHCT. If applied already at indication for CI, the predictive capacity of EASIX is weaker and no longer significant if CAR-T is intended. Further studies for validation of this data appear to be warrantable.
Disclosures: Schmitt: MSD: Membership on an entity's Board of Directors or advisory committees, Other: PI of clinical trials on letermovir; TolerogenixX Ltd: Other: Co-Founder and shareholder; Hexal: Other: Travel grants , Research Funding; Apogenix: Research Funding; Kite: Other: Travel grants, educational activities and conferences; Novartis: Other: educational activities and conferences, Research Funding. Dietrich: Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees. Schmitt: Hexal: Other: Travel grants ; TolerogenixX LtD: Other: Co-founder, Part-time employee ; Therakos/Mallinckrodt: Research Funding; Jazz Pharmaceuticals: Other: Travel grants . Dreger: Neovii: Research Funding; Roche: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy; Gilead: Consultancy, Speakers Bureau; AstraZeneca: Consultancy; AbbVie: Consultancy, Speakers Bureau.
See more of: Oral and Poster Abstracts