Real-world outcomes of elderly patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated with chimeric antigen receptor T-cell (CAR-T) therapy.

Abstract

8039 Background: CAR-T has drastically improved outcomes for R/R DLBCL patients (pts). While CAR-T is now standard of care for the treatment of R/R DLBCL, little is known about its efficacy and toxicity in elderly pts. Methods: We conducted a multi-center retrospective analysis of pts age ≥ 70 years old with R/R DLBCL treated with either axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel). Pt demographics, tumor characteristics, CAR-T data, survival and toxicity outcomes were collected at the time of T cell infusion and follow up. Comorbidities were measured using the cumulative illness rating score (CIRS) and hematopoietic cell transplantation-specific comorbidity index (HCT-CI). Results: A total of 77 pts were analyzed with a median age of 73 (range, 70-88); 30 (39%) pts were age ≥75. Most pts received axi-cel (n = 61, 79%). Unfavorable tumor characteristics included 27 (35%) pts with activated B-cell subtype and 12 (16%) with double/triple hit lymphomas. Median CIRS was 8 (range 0-25) and median HCT-CI was 2 (range 0-9) with significantly higher median CIRS and HCT-CI in pts age ≥75. With a median time to follow up of 5.2 months (m), median progression free survival (PFS) was 12m and median overall survival (OS) was 15.5m. There was no difference in PFS when comparing younger pts (age 70-74) to older pts (age ≥ 75), but median OS was significantly shorter for older pts (7.8m vs. not reached; hazard ratio [HR] 0.46, CI 0.21-0.98; p = 0.04). In a multivariate analysis (MVA) of PFS adjusting for baseline characteristics, HCT-CI > 2 (HR 0.23, CI 0.07-0.77; p = 0.02) and use of axi-cel (HR 0.07, CI 0.02-0.32; p = < 0.001) were associated with worse PFS. Grade 3/4 (Lee criteria) cytokine release syndrome (CRS) and CAR-related encephalopathy syndrome (CRES) were assessed in MVA adjusting for baseline characteristics. CRS was associated with CIRS ≥6 (odds ratio [OR] 3.92, CI 1.07-14.3; p = 0.002) and use of axi-cel (OR 44.9, CI 8.20-245.6; p = 0.006). CRES was associated with older age (OR 6.10, CI 1.86-20.0; p = 0.003), CIRS ≥6 (OR 3.92, CI 1.07-14.3; p = 0.04) and use of axi-cel (OR 44.9, CI 8.2-245.6; p = < 0.0001). Conclusions: Pts age ≥75 treated with CAR-T had worse OS, but comparable PFS as compared to younger pts. Validated frailty measurements (CIRS) predicted for increased CRS and CRES. Use of axi-cel was associated with worse PFS and increased toxicities in the elderly, but propensity matched scoring analysis will need to confirm this. Additional pts and longer follow up are required to validate these results.