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3038 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

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies: Poster III
Hematology Disease Topics & Pathways:
Biological, Diseases, Elderly, CAR-Ts, Therapies, DLBCL, B-Cell Lymphoma, Lymphoid Malignancies, Study Population
Monday, December 7, 2020, 7:00 AM-3:30 PM

Lindsey Fitzgerald, MD1, Adam S. Kittai, MD2, Loretta J. Nastoupil, MD3, Alexandra Waller4*, Caron Jacobson, MD, MMSc5, Anna Saucier6*, Nathan Denlinger, MS, DO7, Manali Kamdar, MD8, Janet Spradley9*, Ryan C. Lynch, MD10*, Jonathan Chipman11* and Boyu Hu, MD11*

1Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
2Division of Hematology, The Ohio State University, Columbus, OH
3The University of Texas MD Anderson Cancer Center, Houston, TX
4Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
5Dana Faber Cancer Institute, Harvard Medical School, Boston, MA
6Dana Farber Cancer Institute, Boston, MA
7Ohio State University Wexner Medical Center, Columbus, OH
8Division of Hematology, Hematologic Malignancies and Stem Cell Transplantation, University of Colorado Cancer Center, Denver, CO
9University of Colorado School of Medicine, Aurora, CO
10University of Washington/Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA
11Huntsman Cancer Institute-University of Utah, Salt Lake City, UT


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.


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.


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 (HRadj 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 (HRadj 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 (HRadj 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 (ORadj 11.14, CI 1.42-87.45; p = 0.02). Similarly, immune effector cell-associated neurotoxicity syndrome (ICANS) was associated with age ≥75 (ORadj 5.14, CI 1.31-20.14; p = 0.02), CIRS ≥6 (ORadj 6.12, CI 1.21-30.88; p = 0.028) and use of axi-cel (ORadj 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).


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.

Disclosures: Nastoupil: Bayer: Honoraria; Gilead/KITE: Honoraria; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; LAM Therapeutics: Research Funding; TG Therapeutics: Honoraria, Research Funding; Merck: Research Funding; Genentech, Inc.: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Gamida Cell: Honoraria. Kamdar: Roche: Research Funding. Lynch: Morphosys: Consultancy; Takeda: Research Funding; Incyte: Research Funding; TG therapeutics: Research Funding; Rhizen: Research Funding; Bayer: Research Funding; Juno: Research Funding; Cyteir: Research Funding; Genentech: Research Funding.

*signifies non-member of ASH