Standard Of Care CD19 CAR T-Cell Therapy in Transformed Indolent Lymphoma Evaluated

In a study of standard of care CD19 chimeric antigen receptor (CAR) T-cell therapy, researchers compared the treatment’s clinical results in relapsed or refractory transformed indolent lymphoma with its performance in de novo diffuse large B-cell lymphoma (DLBCL). It was presented at the 66^th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

“This study represents the largest evaluation to date of outcomes of CD19CAR in [transformed indolent lymphoma], and demonstrates that CAR is highly effective with an acceptable toxicity profile in [transformed indolent lymphoma] patients,” wrote lead author Swetha Kambhampati Thiruvengadam, MD, of City of Hope National Medical Center in Yorba Linda, California.

This multicenter retrospective study defined transformed indolent lymphoma as DLBCL or high-grade B-cell lymphoma. It had a total cohort of 1182 adults, 338 with transformed indolent lymphoma and 884 with de novo DLBCL. All patients had received standard of care CD19 CAR T-cell therapy outside of a clinical trial, 77% having received axicabtagene ciloleucel. The total cohort had a median age at CAR T-cell therapy of 64 years and was 36% female.

The total cohort had a median follow-up of 22.3 months. In the transformed indolent lymphoma and de novo DLBCL groups, the overall response rate was 83% and 81% (P=.3), complete response rate was 67% and 59% (P=.017), 24-month overall survival was 58% and 52% (P=.15), rate of survival at 24 months without progression or relapse was 41% and 38% (P=.16), and cumulative incidence of non-relapse mortality at 24 months was 10% and 11%, respectively.

From patient and treatment factors-adjusted calculations, the study investigators determined the transformed indolent lymphoma group had a 16% lower hazard of disease progression, relapse, or death following CAR T-cell therapy than the de novo DLBCL group (Hazard ratio: 0.84, P=.07). Furthermore, their multivariable analysis found that elevated lactate dehydrogenase, advanced disease stage, having three or more prior lines of therapy, undergoing bridging therapy, prior bendamustine within 12 months of CAR T-cell therapy, and central nervous system involvement before CAR T-cell therapy were each linked to inferior progression or relapse-free survival.

Regarding safety results in the transformed indolent lymphoma and de novo DLBCL groups, the rate of any-grade cytokine release syndrome (CRS) was 79% and 84%, and the rate of grade 3 or higher CRS was 7% and 8%, respectively (P=0.6). The rate of any-grade immune effector cell-associated neurotoxicity syndrome (ICANS) was 42% and 52%, and of grade 3 or higher ICANS was 21% and 27% (P=.024), respectively. The rate of tocilizumab use for CRS was 50% and 61% (P<.001), and of glucocorticoids for ICANS was 36% and 44% (P=.01), respectively.

Reference

Kambhampati Thiruvengadam S, Merryman RW, Wang Y, et al. Real-world outcomes of CD19CAR T cell therapy in adult patients with relapsed refractory transformed indolent lymphoma. Abstract #524. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.