Real World Outcomes of Elderly Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma Treated with Chimeric Antigen Receptor T Cell Therapy: An Updated Analysis

Background:

Chimeric Antigen Receptor T Cell (CAR-T) therapy has drastically improved outcomes for relapsed/refractory (R/R) Diffuse Large B Cell Lymphoma (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 ≥70 years old.

Methods:

We conducted a multi-institutional retrospective analysis of pts aged ≥ 70 years old with R/R DLBCL treated with either axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel). Pt demographics, tumor characteristics, CAR-T infusion data, and survival and toxicity outcomes were collected at the time of T-cell infusion and subsequent follow up. Comorbidities were measured using the cumulative illness rating score (CIRS) and the hematopoietic cell transplantation-specific comorbidity index (HCT-CI). In this updated analysis, the following changes were made: 1) inclusion of pre-CAR-T infusion lactate dehydrogenase (LDH) serum levels, 2) reduction of the number of baseline covariates incorporated into the multivariate analyses for more robust conclusions given sample size, and 3) performed a match-weighted propensity score analysis with axi-cel as the exposure.

Results:

A total of 77 pts were analyzed with a median age of 73 (range, 70-88); 30 (39%) pts were ≥75. Most pts received axi-cel (n=61, 79%). Unfavorable tumor characteristics included 27 (35%) pts with activated B-cell subtype, 52% with an LDH level greater than the upper limit of normal (ULN), 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 older pts (≥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. When comparing patients age 70-74 to those age 75 or older, there was no statistically significant difference in PFS (HR_adj 1.70, CI 0.68-4.25; p=0.25) and OS (HR 1.69, CI 0.64-4.45; p=0.29). Use of axi-cel was associated with improved PFS (HR_adj 0.12, CI 0.04-0.36; p=<0.001) and LDH > ULN was associated with worse PFS (HR 5.07, CI 1.91 – 13.46, p = 0.001) and worse OS (HR_adj 4.88, CI 1.75-13.58, p = 0.002). CRS was associated with CIRS ≥6 (odds ratio [OR]_adj 14.33, CI 2.01-101.9; p = 0.008) and use of axi-cel (OR_adj 11.14, CI 1.42-87.45; p = 0.02). Similarly, immune effector cell-associated neurotoxicity syndrome (ICANS) was associated with age ≥75 (OR_adj 5.14, CI 1.31-20.14; p = 0.02), CIRS ≥6 (OR_adj 6.12, CI 1.21-30.88; p = 0.028) and use of axi-cel (OR_adj 36.38, CI 5.13-258.31; p <0.001). Weighting by propensity-score analysis with CIRS ≥ 6, LDH > ULN, HCT ≥ 2, age, use of bridging therapy, double/triple hit status, and days between collection and infusion, we were able to match 7 patients to compare axi-cel versus tisa-cel. Axi-cel was confirmed to be associated with improved PFS (OR 0.19, CI 0.07-0.53, p 0.001) and higher ICANS grade (OR 16.48, CI 1.35-200.9, p = 0.03).

Conclusions:

In a patient population of ≥70 years old, there was not sufficient evidence to associate pts age ≥75 treated with CAR-T with different OS, PFS, and CRS rates compared to younger pts; however, they had an increased likelihood of developing ICANS. LDH > ULN was associated with worse PFS and OS outcomes. Prior validated frailty measurements (CIRS) was associated with increased CRS and ICANS. Use of axi-cel was associated with improved PFS but increased toxicities in the elderly (age ≥75), which was confirmed by weighted propensity-score analysis. There was not enough evidence, in the propensity-weighted analysis to observe a difference in OS between the use of axi-cel or tisa-cel. Additional pts and longer follow up are required to validate these results.