Naive-like T-cell phenotype linked to longer PFS after CAR T therapy

Researchers analyzed CAR T-cell product characteristics and long-term outcomes in 580 patients with non-Hodgkin lymphoma treated with axicabtagene ciloleucel across multiple clinical trials. Median follow-up was 41.9 months. The primary finding was that a higher proportion of CCR7-positive, CD45RA-positive naive-like T cells was associated with longer progression-free survival (PFS); the hazard ratio for high versus low proportions was 0.46 (95% CI, 0.31–0.68; P=9.8×10−5).

The association remained significant after adjustment for product expansion and was independent of tumor microenvironment characteristics assessed in 112 patients. More prior lines of therapy correlated with a lower proportion of naive-like T cells in both the product and matched apheresis samples. Results were validated in an independent cohort of 203 patients treated with axicabtagene ciloleucel-based therapy or brexucabtagene autoleucel. Analysis of products from 116 patients also linked a CD8 naive-like phenotype without markers including TIGIT, LAG-3, and PD-1 to PFS.

The association was not accompanied by an observed difference in safety. These findings identify a product phenotype associated with outcomes, but do not show that changing treatment timing or selecting products by phenotype improves outcomes. The analysis is not evidence for a new clinical decision rule.