Tandem Meetings 2026 | The largest analysis of real-world outcomes with bispecific antibodies after CAR-T failure in LBCL

We performed a retrospective analysis utilizing the ABC Consortium, which is a consortium of 15 academic centers or CAR T-cell administering centers across the United States. And we identified 830 patients treated with anti-CD19 CAR-T cell therapy, of whom about 51%, in line with historical norms, did experience CAR-T cell failure, either primary refractory or disease relapse post-CAR T-cell therapy. And then of these 429 patients, 64 went on to receive bispecific antibodies as salvage therapy. And so really the reason we did this is because we know that bispecific antibodies are this really wonderful new therapy that’s emerging for large B-cell lymphoma, but of the phase two studies that led to their approval of single agent approval, a very small subset of these had previously been treated with CAR-T cell therapy. And so we really sought to look at the efficacy of efficacy of bispecific antibodies in patients who had previously received CAR T-cell therapy. 

And so overall response rates for bispecific antibodies were actually similar among patients with CAR-T refractory disease and those with CAR-T failure beyond 90 days. So of the patients that we included in this analysis, 30 patients or 47% were treated with epcoritamab, 21% were treated with glofitamab, seven were treated with mosunetuzumab, and 12 patients received these bispecific antibodies in combination with adjunctive therapy. Cytokine release syndrome occurred in seven patients treated with bispecific antibodies, but these were all low-grade, and four patients developed only grade one ICANS. And then overall response rate for patients treated with bispecific antibodies post-CAR T-cell therapy was 54% with a CR rate of 33%. And then we did do a multivariate analysis to kind of look to see what patient factors may correlate with improved progression-free survival and overall survival, and those details are all listed in the paper. But ultimately, I think what we’re looking at here is that bispecific antibodies are an effective therapy post-CAR T-cell therapy. They’re not significantly less effective in the post-CAR T-cell setting than when utilized prior to CAR T-cell therapy. And so this is still a potentially really effective therapy option. And I think, you know, further studies are needed to really demonstrate the proper sequencing of therapy as all these new therapies emerge. But as of right now, while CAR T-cell therapy remains a potentially curative therapy in the second line, I think we now know that bispecific antibodies are an effective therapy to be utilized after CAR T-cell therapy.

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