Noa Biran, MD, offers insights on ongoing research with bispecific antibodies in multiple myeloma.
Noa Biran, MD: There was an abstract recently presented at ASH [American Society of Hematology] using cevostamab, which is a bispecific T-cell engager with a different target, a receptor on the surface of myeloma cells called FcRH5, against the CD3, also on the T cell. Even though it was a relatively small number of patients, it proved the concept that the patients, even with 1 year of treatment and then stopping therapy, were able to see durable remissions even without therapy given the short-term follow-up. We saw more than a 6-month response, but my guess is that it may be much longer with longer-term follow-up.
Then we also have to think about the GPRC5D target, which has quite a different [adverse] effect profile compared with BCMA [B-cell maturation antigen]. And there’s one [drug] right now in development called teclistamab. There are others as well with that target being developed. Regeneron has one. We’re seeing that maybe the risk of infection is lower, but there are other toxicities that can be quite bothersome, such as taste changes, weight loss, and skin changes. And even though they sound mild, and even if they are mild, they can be very, very bothersome to patients and perhaps even limiting in terms of continuation of therapy.
But I think we have to examine different combinations and think about overlying toxicities. How can we minimize toxicity? We don’t want to give 2 drugs that are going to increase the risk of infection. And we don’t want to give 2 drugs that are going to overlap in terms of risk of weight loss and upper GI [gastrointestinal] and taste toxicities. So we have several ongoing studies that have multiple arms. The MajesTEC-7 trial [NCT05552222], for example, compares teclistamab and daratumumab-lenalidomide with daratumumab, Revlimid (lenalidomide), and dexamethasone in patients with newly diagnosed myeloma. The MajesTEC-2 trial has multiple arms looking at teclistamab in combination with daratumumab, bortezomib, lenalidomide, and even triplets and quadruplets with those combinations. We’ll see if we get increased efficacy without overlapping toxicity with these combinations.
Transcript edited for clarity.