Better CAR T-Cell Outcomes Shown in Transformed Follicular Lymphoma Versus DLBCL

Patients with transformed follicular lymphoma (tFL) showed a distinct survival advantage compared with patients with de novo diffuse large B-cell lymphoma (dnDLBCL) after receiving chimeric antigen receptor (CAR) T-cell therapy, according to a study presented by Matthew Cortese, MD, MPH, at the 66th American Society of Hematology Annual Meeting & Exposition.

Dr. Cortese also reported that CAR T-cell therapy “appears to overcome some of the adverse prognostic impact” of “double hit” lymphoma (DHL) in patients with tFL.

The study included 691 patients treated with CD19-directed CAR T-cell therapy at 14 academic institutions in the United States with follow-up until June 30, 2024. Of the patients, 552 had dnDLBCL, including 88 with DHL and 90 with “double expressor” lymphoma (DEL) status, and 139 had tFL, including 27 with DHL and 22 with DEL.

CAR T-Cell Therapy for Transformed Follicular Lymphoma or De Novo DLBCL

There were no significant differences in median age, sex, race, Eastern Cooperative Oncology Group  (ECOG) performance status, International Prognostic Index (IPI) score, or median prior lines of therapy between the two groups. Rates of prior autologous transplant, bridging therapy, DHL or DEL status, and primary refractory disease or early relapse within one year were also comparable.

Compared with the dnDLBCL group, fewer patients with tFL received anthracycline-based therapy (66% vs 87%); instead, more received bendamustine-based therapy (24% vs 6%). The 33 patients with tFL and prior bendamustine exposure had a three-year overall survival (OS) rate of 51% compared with a rate of 61% in those without prior exposure (P=.15).

At a median follow-up of 29.3 months, CAR T-cell therapy yielded significantly improved three-year OS (59% vs 39%; P<.01) and three-year progression-free survival (PFS) rates (54% vs 39%; P<.01) in patients with tFL compared with dnDLBCL. In the primary refractory disease or early relapse subgroups, patients with tFL had improved three-year OS (51% vs 35%; P=.02) and three-year PFS rates (46% vs 35%; P=.04) versus those with dnDLBCL.

A survival difference was also seen between the DHL subgroups for three-year OS (tFL, 57%; dnDLBCL, 39%; P=.03) and three-year PFS (tFL, 50%; dnDLBCL, 39%; P=.06)—an interesting finding according to Dr. Cortese. Comparatively, patients with DEL disease had worse three-year OS (tFL, 33%; dnDLBCL, 37%; P=.63) in both groups.

“The clinicopathologic and molecular features underlying these differential responses requires further investigation,” Dr. Cortese and colleagues suggested.

Reference

Cortese MJ, Herr MM, Nair N, et al. Clinical outcomes of transformed follicular lymphoma with CAR T-cell therapy: a US multicenter real-world analysis. Abstract #525. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.