Transcript
Before we jump in, I want to acknowledge that ASH 2025 showcased important advances across multiple targets, including non-BCMA agents like cevostamab. This remains an essential part of our toolbox and will become more important over time. But I think in day-to-day practice, BCMA remains the most practical and widely used, most effective target, especially with the rapidly evolving CAR-T and bispecific options. In this next section, I’m going to focus on a key BCMA bispecific update.
So we learned from an oral ASH abstract—results from the MajesTEC phase III trial—this trial included, teclistamab and daratumumab in relapsed/refractory patients. The trial compared teclistamab plus sub-Q daratumumab (tec/dara) to current standard combinations, such as dara/pom/dex or dara/velcade/dex, and the results were very clear. So progression-free survival was significantly improved with tec/dara. We also saw early signs of overall survival and responses much deeper, with higher rates of VGPR or better, and meaningful MRD negativity rates in patients. Why does this matter for us as APPs in practice? I think this really positions the use of a BCMA bispecific, such as teclistamab plus daratumumab, a very important backbone in all of our myeloma therapy, as a potential second-line standard for those patients who are refractory to lenalidomide. So this is a big shift, being able to use a bispecific antibody in second line. Right now, we’re most familiar with using our bispecific antibodies in fourth line or more, but this is going to rapidly change.
Second, I think this introduces some real sequencing questions. So, at first relapse, we typically think about CAR-T in a high-risk patient, or another combination of our more standard myeloma drugs. If and when we get approval with tec/dara, we’ll be able to think about using a bispecific in this earlier space. And I think certainly there’s going to be patient populations who this is very important for. This means that APPs, we must guide our conversations about if and when this might be the potential treatment to use. You want to think about whether the patients had anti-CD38 exposure, so remember in MajesTEC-3, the patients enrolled in the trial had not had prior daratumumab exposure. We want to think about infection risk for patients, how frequently do they want to be or are they able to be in clinic. We want to think about their caregiver support, and then, of course, always include the patient preference in shared decision-making.
On the management side of this regimen, we saw from the trial that the safety profile is pretty consistent with what we know. CRS was mostly low grade and concentrated during the step-up doses of teclistamab, cytopenias were common, and then that infection risk remains real. For many community practices, as we are able to institute this, this will require building or updating our current bispecific orders, modifying, perhaps, the step-up protocols, redefining our CRS escalation pathways, and then having standard antimicrobial prophylaxis.
The real-world presentations at ASH reinforce that teclistamab can be safely delivered in the outpatient and hybrid models, especially when there are APP- and pharmacy-driven protocols, and the escalation pathways are clear.
I think the bottom line here with MajesTEC-3, it really positions teclistamab or a BCMA bispecific alongside daratumumab as a big contender for a really effective second-line therapy. For APPs, this means we need to continue to master the logistics of bispecific care from infection prevention. We need to inform patients about sequencing decisions, and then prepare our clinics for a future where bispecifics are used much earlier.
