CAR-T Meeting 2022 | Updates on CAR-T therapies in NHL: real-world data, trials & new indications

So, non-Hodgkin lymphoma represents, nowadays, the most frequent indication for treatment with CAR-Ts. And in fact, non-Hodgkin lymphoma patients are around 80% of the patients that have been reported to the EBMT registry, because of this specific treatment. So, nowadays, we have really consolidated data regarding long-term outcome and efficacy of the three different CAR-T constructs that we have for non-Hodgkin lymphoma, based on the data of the ZUMA-1 trial, the JULIET trial, and the TRANSCEND trial.

This data has allowed us to use CAR-T outside prospective clinical trials and the real-world data that we have nowadays coming from the US, and also coming from Europe have been able to reproduce quite well the efficacy data that we have in the pivotal trials, in the same way that the toxicity and the safety profile seems quite similar. And also the data coming from real-world and the long-term outcome data coming from the pivotal trials, have allowed us to establish or to understand some specific prognostic factors that are able to differentiate different subpopulations of patients that do better or worse with CAR-T therapy. And because of these excellent and really promising results of CAR-T in patients that have failed, at least, two prior lines of treatment, basically aggressive, large B-cell lymphoma, nowadays, we are seeing the possibility to move these CAR-T constructs either to earlier phases of the diseases or to different histologies. In the last ASH meeting, we had the positive results of two out of three prospective clinical trials that compared the three different constructs with the standard of care, so basically chemoimmunotherapy plus autologous stem cell transplantation in patients with primary refractory or early relapsed diffuse large B-cell lymphoma, and maybe in these specific groups of patients, the standard of care will change. CAR-T were able to offer better results in terms of event-free survival than the standard of care.

We have also seen the possibility to use CAR-T in the context of first-line treatment, in high-risk patients with aggressive large B-cell lymphoma. And we also have data coming from pivotal trials indicating the effectiveness of Tecartus, brexucabtagene in patients with relapsed/refractory mantle cell lymphoma, patients that have failed BTK inhibitors, and this is another indication that we have been able to start using in Europe. And we will have probably new indications in the future, basically looking at follicular lymphoma. In summary, the perspective with the use of CAR-T products in patients swith non-Hodgkin lymphoma is already bright and probably is going to be brighter in the future.