What Are the Survival Outcomes of Transformed Follicular Lymphoma After CAR-T?

CD19-directed chimeric antigen receptor (CAR) T-cell therapy led to improved survival in patients with transformed follicular lymphoma (FL) compared to patients with de novo diffuse large B-cell lymphoma (DLBCL), according to a retrospective, multicenter cohort study.

The results were presented by Matthew J. Cortese, MD, MPH, of the Roswell Park Comprehensive Cancer Center in Buffalo, New York, and presented at the 66th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

The 691 patients included in the study were further classified by double hit lymphoma (DHL) or double expressor lymphoma (DEL) status. Median age (60 years), gender, race, ECOG performance status, International Prognostic Index score, primary refractory disease (14% vs 16%) or early relapse less than one year after frontline therapy (28% vs 27%), requirement for bridging therapy, and DEL or DHL status were comparable across the DLBCL and FL groups.

Both groups had a median of two prior lines of therapy. Fewer patients with FL received anthracycline-based therapy compared to those with DLBCL (66% vs 87%, respectively), while more patients with FL received bendamustine-based therapy (24% vs 6%, respectively). The three-year overall survival (OS) rate of patients with FL with prior bendamustine exposure was 51%, compared to 61% without bendamustine (P=.15).

At 180 days after CAR-T, the overall response rate was 52% for FL and 36% for DLBCL. The complete response rate was 45% for FL and 31% for DLBCL. Fewer patients with FL than DLBCL relapsed after CAR-T (56% vs 40%, respectively; P<.01). The median time to relapse (98 days vs 91 days, P=.16) and CD19-negativity at relapse (39% vs 35%; P=.68) were comparable between the FL and DLBCL groups, respectively.

At a median follow-up of 29.3 months, the three-year OS and progression-free survival (PFS) were superior in patients with FL compared to DLBCL. The OS and PFS was 59% and 54% for FL, respectively, compared to 39% and 35% for DLBCL, respectively (both P<.01). In those with primary refractory disease or early relapse, the three-year OS was 51% in the FL group versus 35% in the DLBCL group (P=.02), and the three-year PFS was 46% in the FL group versus 35% in the DLBCL group (P=.04).

Finally, the researchers observed trends in survival outcomes between the DHL and DEL subgroups. Patients with DHL in the FL group had a better three-year OS (57% vs 39%, respectively; P=.03) and PFS (50% vs 39%, respectively; P=.06) than those with DHL from the DLBCL group.

However, those with DEL had inferior survival outcomes regardless of cohort, with a three-year OS of 33% in the FL cohort and 37% in the DLBCL cohort (P=.63).

“CAR-T appears to overcome some of the adverse prognostic impact of DHL in [transformed] FL [patients],” the researchers concluded. “The clinicopathologic and molecular features underlying these differential responses requires further investigation.”

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.