A second-generation anti-CD19 chimeric antigen receptor (CAR) T-cell (CAR-T) therapy showed clinical benefit and low toxicity in a small group of patients with B-cell lymphoma in a phase 1 trial (ClinicalTrials.gov identifier NCT02842138). The trial results were published online in Nature Medicine.
In the single-arm trial, 26 patients with B-cell lymphoma were enrolled to receive a second-generation CD19 CAR-T cell therapy, referred to as CD19-BBz(86). One patient did not receive the therapy because a sufficient number of CAR-T cells could not be manufactured.
Three doses of infused CD19-BBz(86) CAR-T were evaluated: 3–6 × 106, 6–19 × 107, and 2–4 × 108 total CD19-BBz(86) CAR-T cells. For the lowest dose of 3–6 × 106 total CD19-BBz(86) CAR-T cells, responses were seen in 3 of 6 patients. For the intermediate dose of 6–19 × 107 total CD19-BBz(86) CAR-T cells, partial responses were seen in 4 of 8 patients. For the highest dose of 2–4 × 108 total CD19-BBz(86) CAR-T cells, responses were seen in 8 of 11 patients (72.7%), with 6 (54.5%) achieving a complete response and 2 (18%) achieving a partial response. Among the patients who achieved a complete response, the duration of response ranged from 162 days to 290 days.
As for adverse events, 7 of 25 patients had grade 1 cytokine release syndrome, none of which required medical intervention. No patients had higher-grade cytokine release syndrome and no patients had neurological toxicity of any grade.
“Thus, therapy with the new CD19-BBz(86) CAR T cells produces a potent and durable antilymphoma response without causing neurotoxicity or severe CRS, representing a safe and potent anti-CD19 CAR T cell therapy,” the study authors wrote in conclusion.
- Ying Z, Huang XF, Xiang X, et al. A safe and potent anti-CD19 CAR T cell therapy [published online April 22, 2019]. Nat Med. doi: 10.1038/s41591-019-0421-7