Novel anti-CD19 CAR T-Cell therapy shows efficacy in multiple BCL subtypes

Manali Kamdar, MD, MBBS, assistant professor of medicine-hematology and clinical director of lymphoma services at the University of Colorado Medicine, discusses the efficacy and tolerability of a Phase 1 clinical trial testing a new antigen receptor chimeric anti-CD19 (CAR) T-cell product in adults with relapsed/refractory (R/R) B-cell lymphoma (BCL).

The phase 1 trial investigated a new CD19-targeted CAR-T cell therapy in several subtypes of BCL, including marginal zone lymphoma, follicular lymphoma, transformed lymphoma and diffuse large BCL. One of the 7 patients treated with CAR T cells required a second apheresis.

At 90 days, 6 of 7 patients had a complete metabolic response, with one having progressive disease at 180 days, while 5 maintained remission for more than 12 months. Flow cytometry showed maximum expansion of CAR T cells at days 5–15, and cell persistence continued for these 5 patients through day 180.

Kamdar says toxicity was manageable for this CAR T cell product, with 2 patients suffering from Grade 2 cytokine release syndrome (CRS) and 1 patient suffering from Grade 2 neurotoxicity. However, no Grade 3 or higher toxicity has not been reported. Overall, this therapy has shown high efficacy and tolerability, and the trial continues to enroll patients.

TRANSCRIPTION:

0:08 |Regarding toxicity, the safety profile was very manageable. Two patients presented with grade 2 CRS; 1 patient experienced Grade 2 neurotoxicity. No Grade 4, Grade 3, or 5 CRS or neurotoxicity was reported. No new security signals were even detected. Flow cytometry was used to measure expansion and persistence of CAR T cells in 5 patients. We noticed that the peak expansion of CAR T cells ranged from day 5 to day 15. Cell persistence was detected [in] 4 to 5 patients until at least day 180.

0:45 | In conclusion, 7 patients diagnosed with 5 different subtypes of B-cell non-Hodgkin’s lymphoma have so far been treated with this CD19 CAR T-cell product. Manufacturing was successful for all patients. There were no safety-related out-of-specifications and no new post-infusion safety signals were detected… To date, 6 out of 7 patients are still alive, with 5 patients in complete metabolic response. Obviously, this phase 1 study looks very promising both in terms of its efficacy and its safety profile. It continues to register, so we hope to present follow-up data at future meetings.

Irene B. Bowles