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The 2022 Tandem Meetings | Bispecific anti-CD20, anti-CD19 CAR-Ts for R/R NHL

Nirav Shah, MD, Medical College of Wisconsin, Milwaukee, WI, comments on the results of a study evaluating bispecific anti-CD20, anti-CD19 CAR-Ts for relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). Dr Shah explains that these CAR-Ts have optimized manufacturing characteristics, with different reagents used and a shorter manufacturing time. The study reported an overall response rate (ORR) reaching 90%, with a low incidence of grade 3 or higher cytokine release syndrome (CRS) or neurotoxicity. The study also assessed the efficacy of these CAR-Ts in mantle cell lymphoma (MCL), where patients achieved an ORR of 100%, without any case of relapse. A Phase II trial evaluating this product in a larger patient population is currently underway. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT™ and CIBMTR® 2022 in Salt Lake City, Utah.

Transcript (edited for clarity)

So we know that single targeted CD19 CAR-Ts are incredibly effective for the treatment of B-cell malignancies. But one escape mechanism is loss of CD19 and development of a clonal escape in a population that is CD19 negative. For many years, now, our group has been working with a dual-targeted bispecific anti-CD20, anti-CD19 CAR-Ts. So this is a follow up trial where we basically optimized the manufacturing characteristics, increased the depth of lymphodepletion to basically try to improve outcomes from a prior study...

So we know that single targeted CD19 CAR-Ts are incredibly effective for the treatment of B-cell malignancies. But one escape mechanism is loss of CD19 and development of a clonal escape in a population that is CD19 negative. For many years, now, our group has been working with a dual-targeted bispecific anti-CD20, anti-CD19 CAR-Ts. So this is a follow up trial where we basically optimized the manufacturing characteristics, increased the depth of lymphodepletion to basically try to improve outcomes from a prior study. So in this study, we use different reagents to manufacture the CAR-Ts. And then we studied varying lengths of manufacturing time. This product was very effective in our clinical trial, which we’ll be discussing at our presentation today. The overall response rate was above 90% for all patients. And many of those responses were durable in terms of toxicity. There was only one grade 3 CRS, and the entire population of 29 patients and only three patients with grade 3 or higher neurotoxicity. Some of the exciting findings that we had is that we did find that a shorter manufacturing product did skew the CAR-Ts towards a more immature or T stem cell memory phenotype. So we do think that’s a better CAR-T product. And another exciting finding is we had a small Phase II arm in mantle cell, we’ve treated 10 patients. And the overall response rate was 100% in that population. And with the median follow up of 14 months, not a single patient has relapsed. So really some exciting findings with this dual-targeted CAR. We’re working with Miltenyi which is an industrial company, pharmaceutical company, and they have an ongoing Phase II multicenter trial to evaluate this product at a larger scale.

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