Real-World Study Suggests Cell of Origin in DLBCL May Impact Response to CAR-T Therapy

By Kerri Fitzgerald - December 21, 2022

A study presented at the 2022 American Society of Hematology Annual Meeting assessed the efficacy of chimeric antigen receptor (CAR) T-cell therapy in patients with diffuse large B-cell lymphoma (DLBCL) and observed that the cell of origin may impact response and survival.

There are two major subtypes of DLBCL based on the cell of origin: germinal center B-cell-like (GCB) and activated B-cell-like (ABC). Approximately 10% to 15% of cases cannot be classified and are referred to as not otherwise specified (NOS). Previous studies have shown a more favorable prognosis for patients with GCB DLBCL.

In this retrospective, multicenter study, researchers assessed outcomes for 99 patients with DLBCL treated with CAR T-cell therapies to determine 12-month progression-free survival (PFS) based on tumor biology: GCB (n=50), NOS (n=39), and ABC (n=10).

Baseline characteristics did not appear to differ among the three cohorts. The median patient age was 65 years, 87% were white, and 62% were male. Patients received a median of three lines of treatment prior to CAR-T.

Median PFS was not achieved for the ABC subtype, 4.6 months for the GCB subtype, and 3.5 months for the NOS group (P=.34), suggesting “there may be a trend toward a greater PFS benefit for those with the ABC subtype,” according to the researchers. Median overall survival was 14.8 months, 13.4 months, and eight months, respectively (P=.083).

Complete responses occurred in 50% of patients with the ABC subtype, 32% with the GCB subtype, and 26% with the NOS subtype (P=.34). Progressive disease after CAR-T occurred in 51% of patients with NOS subtype, 32% of those with GCB subtype, and 20% with ABC subtype (P=.34).

The researchers noted that the small number of patients in the ABC subgroup limits the ability to determine a meaningful result from the outcomes. Overall, the study is also limited by a small sample size.

“In addition, the percentage of patients in the NOS group in this study (~39%) was much higher than the number reported in the literature (~10-15%),” the study’s authors noted. “This could be due to the retrospective nature of the study making it difficult to obtain cell of origin information from the time the diagnosis was made and leading to a patient being classified as NOS when they may have had a GCB or ABC subtype.”

The researchers indicated that future studies with larger cohorts should continue to examine CAR-T response by cell of origin in DLBCL, “as this may influence patient treatment selection,” they concluded.


Brinkman L, Wagner CB, Ying J, et al. CAR-T therapy in patients with relapsed or refractory diffuse large B cell lymphoma: real world outcomes based on tumor biology. Abstract #4296. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.

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