CD19/CD22 chimeric antigen receptor T-cell (CAR-T) cocktail therapy is safe and effective in patients with refractory/relapsed (R/R) B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), according to the results of a phase 1/2 clinical trial (NCT05206071).

“Our current study has demonstrated promising clinical efficacy and manageable toxicity of a mixed infusion of CAR19/22 T-cell cocktail in patients with R/R [B-cell non-Hodgkin lymphoma],” the study authors wrote in Cells. “In parallel, we also compared efficacy and safety results among two groups of patients that received either a humanized or a murinized version of this cellular product.”

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Both the humanized and murinized cohorts achieved robust responses to therapy. On day 28 postinfusion, 91.7% of patients had achieved an objective response in the humanized cohort, with most (75%) showing a complete response (CR) and 16.7% having partial responses. In the murinized cohort, half of the patients showed a partial response and 42.9% achieved a CR.

Most (75%) patients in the humanized cohort maintained a CR at the 3-month evaluation, while the overall response rate and CR rate in the murinized cohort were 57.1% and 35.7%, respectively. Further group analysis showed that patients with a TP53 mutation who received a humanized cell infusion had a higher response rate than those who received murinized CAR-T (80% vs 33%, respectively), presenting a response rate similar to that observed for TP53 mutation-negative patients (78.6%).

Moreover, the murinized cohort had a median progression-free survival (PFS) of 140 days, whereas the humanized cohort had not reached the median PFS at the cutoff date (median follow-up, 330.5 days).

Nearly all (96.2%) patients experienced cytokine release syndrome, though 88.5% of cases were mild or low grade. Furthermore, 15.4% of patients experienced immune effector cell-associated neurotoxicity syndrome.

No fatal adverse events (AEs) or treatment-related deaths were reported. Severe AEs were mostly cases of cytopenia, which were managed in accordance with protocol-specific guidelines.

The study enrolled 32 patients with R/R B-cell non-Hodgkin lymphoma, though 6 patients were excluded due to rapid disease progression. Of the 26 patients remaining in the study, most (n=20) had a diagnosis of DLBCL. Fourteen patients (DLBCL, n=10) received the murinized CAR19/22 cocktail infusion and 12 (DLBCL, n=10) received the humanized version.

References

Huang L, Li J, Yang J, et al. Safety and efficacy of humanized versus murinized CD19 and CD22 CAR T-cell cocktail therapy for refractory/relapsed B-cell lymphoma. Cells. Published online December 16, 2022. doi:10.3390/cells11244085

Clinical study of SL19+22 CAR-T cells for relapsed or refractory non-Hodgkin lymphoma. ClinicalTrials.gov. January 25, 2022. Accessed December 28, 2022.