ASH 2024 | Cevostamab in patients with triple-class refractory MM after prior BCMA-targeted bispecific antibody

So, in this study, we have looked at the role of cevostamab, which is an antibody that targets FCRH5 and CD3, in heavily pre-treated myeloma patients who were triple-class refractory and who were prior treated with another bispecific antibody. So in brief, that study had several cohorts. So one cohort was with patients who got prior treatment with antibody drug conjugate and CAR-T treatment and this cohort with prior bispecific antibody treatment. Patients received step-up dosing and then the therapeutic dose was given every three weeks at the optimal dose of 180 milligrams. Now in terms of safety we found that cevostamab was also very well tolerated in terms of the CRS events, in terms of bone marrow suppression, this was all very comparable with the other cohorts. And given the fact that patients had received in this cohort a median of eight prior lines of therapy, the overall rate of severe infections was very acceptable. It was only 29%. Now in terms of efficacy, these results were more disappointing compared to the other cohorts because the overall response rate was only 10% in patients who received a bispecific antibody after another, despite a washout period of at least three months. So we also did some correlative science in this particular cohort. And what we found is that there was high expression of immune exhaustion markers, like PD-1, like TIGIT. And that was much more pronounced in this cohort of one bispecific, so cevostamab after another bispecific antibody, compared to the other cohorts where patients received cevostamab post-antibody drug conjugate or post-CAR T. And that really emphasized, let’s say, that we also need a very functional immune system to make a bispecific antibody work, even if it’s an active antibody like cevostamab. Thanks for your attention.

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