medwireNews: The CD-19/CD-20 bispecific chimeric antigen (CAR)-T cell therapy prizlo-cel, formerly JNJ-90014496, shows high response rates in patients with relapsed/refractory (R/R) CAR-T-cell-naïve patients with large B-cell lymphoma (LBCL), irrespective of CD-19 and CD-20 antigen levels and immunosuppressive tumor microenvironment archetypes, shows a phase 1b study.
Presenter Mahipal Suraneni (Johnson & Johnson, San Diego, California, USA) told delegates at the 67th ASH Annual Meeting and Exposition in Orlando, Florida, USA, that the findings indicate that with its “optimized CAR design,” prizlo-cel may prevent relapses due to antigen loss and address the challenge of tumor heterogeneity, which in turn “may overcome limitations of single-antigen targeting CAR-T cells, with a potential to improve clinical outcomes.”
He explained that prizlo-cel binds CD19, with a transmembrane CD28 domain and a 4-1BB costimulatory domain, and it also has a differentiated CD20 binder that targets the membrane-proximal epitope on B cells, which together “may improve synapse formation and T cell activation.”
As previously reported at the EHA congress in June 2025, treatment with prizlo-cel in patients with R/R LBCL, who had not received prior CAR-T cell therapy, achieved high rates of complete response (CR) across all doses tested (200 x 106 cells/kg, 150 x106 cells/kg, and 75 x106 cells/kg), irrespective of the number of prior lines of therapy. The objective response rate (ORR) was 91% and the complete response (CR) rate was 75%.
It also had a “favorable safety profile,” commented Suraneni, with few grade 3 cases of immune-effector cell-associated neurotoxicity syndrome (ICANS) or cytokine-release syndrome (CRS), “even in the absence of prophylactic steroids.”
For the current analysis, Suraneni and team studied biomarker data to see if any correlated with clinical outcomes in 51 of the patients.
They found that CAR-T cell expansion and persistence were comparable across the doses tested, and there was no significant dose effect on the number of CD4+ or CD8+ cells at peak expansion. Also, median B cell depletion occurred around day 5 and this was again consistent across the doses. Together, these features “drive strong efficacy,” said Suraneni.
Neither CAR-T cell expansion, nor the depth of response were dependent on CD19 and CD20 expression levels, “remaining high in patients with low expression of either antigen.”
Specifically, in 42 patients analyzed, 31 had medium-to-high levels of CD19 and CD20 expression, based on a histochemical score of 100 or above, while 11 had low levels of CD19 and/or low levels of CD20, but CAR-T expansion was similarly high in both groups.
The ORR was also high in patients with medium-to-high and low levels of CD19 and CD20 expression, at 100% and 82%, respectively, as was the CR, at 90% and 73%. This was the case even in 7% of patients who had low levels of both CD19 and CD20. This confirms the effective dual targeting of both antigens, the presenter pointed out.
Suraneni went on to discuss the treatment effects according to the three recently characterized lymphoma microenvironment archetype profiles, or LymphoMaps, for detecting clinical response, namely, lymph node (LN) architectural cell types with naïve and memory T cells supporting an immune environment; FMAC, with a sparsity of T cells and a high frequency of cancer-related fibroblasts and tumor-associated macrophages; and TEX, with activated macrophages and exhausted CD8+ T cells.
With standard of care CAR-T cell therapies, LN was associated with better efficacy than FMAC and TEX, but CR rates with prizlo-cel were 94% among 16 LN patients, 83% among six FMAC, patients and 88% among eight TEX patients. The “consistently high” CR rate is “potentially differentiating prizlo-cel from standard of care CD19 CAR-T,” said the presenter, by “overcoming immune cell suppressor tumor microenvironment and these findings warrant further investigation.”
