Managing Quality-of-Life Toxicities and Optimizing Sequencing in Dual-Bispecific Therapy for EMD

In discussing real-world considerations for talquetamab (Talvey; Johnson & Johnson)-teclistamab (Tecvayli; Johnson & Johnson) combination therapy, Saad Usmani, MD, MBA, FACP, FASCO, emphasizes that proactive counseling and multidisciplinary support are essential, as nearly 80% of patients experience low-grade yet adherence-threatening toxicities such as taste changes and skin or nail effects. Pharmacists play a key role in early symptom recognition, guiding dose adjustments, and coordinating nutrition and supportive care services.

Usmani also underscores how sustained efficacy in patients previously treated with CAR T-cell therapy or other bispecifics supports preferential use of dual-targeting strategies in difficult-to-treat populations, while emerging evidence on tumor volume highlights the value of assessing and cytoreducing high-burden disease before initiating combination bispecific therapy.

Q: With nearly 80% of patients experiencing taste changes, skin/nail toxicities, or other low-grade but quality-of-life–impacting adverse events, how should pharmacists counsel patients and caregivers to maintain adherence and manage these treatment-emergent effects?

Saad Usmani, MD, MBA, FACP, FASCO: Early recognition and then dose delays or even stretching out the dosing based on symptom resolution would be important. I think it's also important to appreciate that this is a multidisciplinary effort, so it might be important to have a nutritionist counsel patients on what they can have in terms of making sure that they get their caloric intake. Getting advice on how to manage those side effects is going to be important as well.

Q: Considering that talquetamab-teclistamab maintained efficacy even in patients with prior CAR-T or prior bispecific exposure, how do you see these influencing treatment sequencing recommendations?

Usmani: Given the fact that if you treat patients with either a BCMA or a GPRC5d bispecific and only get about 5-odd months of progression-free survival benefit based on the clinical trial data availability, I think it's going to be very important for us to actually use this combination preferentially for patients. It's not a big proportion of patients, but it is a very difficult-to-treat population of patients, so my preference would be dual targeting for these patients.

Q: How could tumor volume assessments be integrated into the decision-making, the education, and patient expectations?

Usmani: One thing that we are recognizing is that when patients are presenting with extramedullary disease and they have a high burden, we may need to reduce that disease burden with conventional chemotherapy before we start the bispecific directed treatments, and that's what we're starting to employ. So, this is the first study that is actually providing guidance on looking at the disease volume. In my practice, you know, I would start looking at patients who have more than 25 cm² of tumor burden and think about cytoreducing them before I put them on bispecific dual targeting the way that it was done in the RedirecTT-1 study.