ASH 2024 | Cevostamab in patients with heavily pretreated R/R myeloma: updated results from a Phase I trial

Yeah, so I’m really excited to see this study get presented. So, cevostamab is an FcRH5 CD3 bispecific T-cell engager. The study was a first-in-human dose escalation study for patients with refractory multiple myeloma. There were multiple cohorts evaluated, multiple step-up doses and target doses, and overall over 300 patients were actually enrolled on this study. The target dose, 160 milligrams was achieved, or 167 patients actually received that dose through and achieved that dose through a variety of step-up schedules, including two step-up doses as well as three step-up doses. The recommended phase two from this dose will be the three step-up dose regimen with 160 milligrams administered. 

So the data actually presented here in this abstract is the safety as well as preliminary efficacy data from this cohort of patients. So of course the main adverse effect that these patients experienced was CRS, or cytokine release syndrome, which was experienced in approximately 50% of patients, with the majority of these events being grade one. Infections were also observed, but the majority of them were non-serious infections. Serious infections as well as some fatal infections were actually observed on the protocol as well. 

The patient population overall though was heavily pre-treated with a total group of patients having received six prior lines of therapy. The majority were pentadrug refractory and over half have had received prior BCMA-directed treatments. And so, in this heavily pretreated patient population, you know, having this novel therapy is an advance for the field. So, the response rates overall were, for the 167 patients, were approximately 44%, with a quarter of these patients achieving VGPR or better. However, in individuals that had not received prior BCMA-directed therapy, the response rate was 60%, whereas those that received prior BCMA-directed therapy, the response was lower in the low 30%. Duration of response for those that achieved the VGPR or better was over 21 months or so. 

So I think this study represents sort of a novel target, a CD3 T-cell engaging therapy that’s not directed at BCMA, not directed at GPRC5D. So it’s another option for our patients. And it is active and leads to durable remission. One thing I should also add is this study was designed for a fixed duration of treatment where individuals received 17 cycles of treatment with a treatment once achieved to the target dose every three weeks. This was approximately one year of therapy, and among individuals that completed all the therapy, responses were quite durable off treatment, especially among individuals who achieved a complete remission with the majority of those maintaining response for more than six months.

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