CAR-T Meeting 2025 | Treatment failure patterns in second-line versus third-line introduction of CAR-T therapy in LBCL

CAR T-cell therapy has obviously transformed the care of large B-cell lymphoma. And as the treatment advances and we treated more and more patients and we saw that it was highly efficacious in the third line setting, it led to clinical trials studying it in second line setting. So we have studies looking specifically at axicabtagene ciloleucel and lisocabtagene maraleucel in second line, where we see that compared to the standard of care, the patients that got CAR T-cell products actually did better with respect to their PFS overall. So that was the rationale of introducing CAR T-cells earlier on in the course of the patients. 

We asked a slightly different question. So we didn’t ask what’s the better intervention in second line. We asked whether the outcomes of patients treated with CAR-T in second line were in fact better compared to patients treated in third line. And the question that was of most interest to us is about relapse pattern. 

In a study recently published by Magdalena Corona, what we found is that in fact patients treated with CAR T-cells for large B-cell lymphoma at second line versus those treated at third line had better overall survival. However relapse patterns or relapse incidence was completely overlapping with about a one-year relapse incidence of 40 percent and this was consistent even after adjusting for potential confounders and also despite the fact that the patients treated in third line were enriched for adverse factors. So what it tells us is that there may be some inherent mechanisms of resistance that are selected after failure of first-line therapy. And we need to get a better understanding essentially of the biology of what’s driving CAR T-cell failure.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.