ASH 2023 | Anti-CD19 CAR-T for Richter’s transformation: an international multicenter retrospective study

Richter’s transformation is when CLL turns into an aggressive lymphoma, most often large B-cell lymphoma. Richter’s transformation is associated with dismal outcomes where there really is no standard of care therapy. So as we know, CAR T-cell therapy has revolutionized the way that we treat large B-cell lymphoma and it’s now approved in the second line for diffuse large B-cell lymphoma. But in those clinical trials that led to his approval, Richter’s transformation was mostly excluded. And so we sought to determine, if the CAR-T works for diffuse large B-cell lymphoma, maybe it works for Richter’s transformation as well, especially that Richter’s transformation, the treatment is really modeled after the treatment of diffuse large B-cell lymphoma. 

So previously we reported our study looking at nine patients with Richter’s transformation, and we treated them with Axicabtagene ciloleucel or axi-cel, one of the CD19-directed CAR T-cell therapies. And we found that eight out of nine patients had responded to the drug. And so given this preliminary data, we thought it best if we did a multicenter study to look at long-term responses to CAR T-cell therapy in a larger patient population, because Richter’s transformation is generally rare. And so we were able to work with 11 different institutes across the United States and Australia. We found 69 patients with Richter’s transformation that were treated with CAR T-cell therapy. So of those 69 patients, the most of them were actually clonally related. So clonally related is when the CLL literally transforms to Richter’s transformation into an aggressive lymphoma, and it’s associated with poor outcomes, and it’s classically the most prognostic factor that’s associated with poor outcomes with Richter’s. So of the 69 patients, about 40% had a complete response, 15% had a partial response, and 30% had progressive disease as their best response. And what we found was that the median PFS was around four months, and the median overall survival was eight months. So this data wasn’t as impressive as we hoped it would be. And what we also found that was very interesting was that the patients who attained a complete response had a very long duration of response of 27 months. 

So there are a select group of patients that do really well with CAR T-cell therapy for Richter’s transformation. So I don’t think all is lost. We just have to figure out which of those patients are most likely to respond to CAR T-cell therapy. And once again, these patients really had no other options at this point. They had received already two prior therapies for the Richter’s. And so really, I think CAR T-cell therapy should continue to be used, we should continue to work on when best to implement the CAR T-cell therapy, and we should really figure out which of those patients are most likely to respond to the treatment.