Bispecific Antibodies Get ‘Fantastic’ Responses in Pretreated Myeloma

Bispecific antibodies are eliciting impressive responses among patients with pretreated multiple myeloma, as one expert explained.

“Regardless of the actual bispecific therapy, just know that we're having excellent response rates,” explained Dr. Brandon Blue, a clinical instructor in the Department of Malignant Hematology at the Moffitt Cancer Center in Tampa, Florida. “So, the majority of the people who are getting these therapies are responding, which is what we all want because again, these are not for people at the beginning [of treatment]. These are people who have seen four, five, six, seven lines of therapy, and [we are] still able to see it work in such a high amount of people.”

Blue, serving as the summit chair for CURE®’s Educated Patient® Multiple Myeloma Summit, discussed a presentation prepared by his Moffitt Cancer Center colleague Dr. Ariel F. Grajales-Cruz, an assistant member of the Malignant Hematology, Myeloma Section.

He explained the science behind bispecific antibodies, which work by bringing healthy T cells — part of the body’s immune system — to myeloma cells. The goal is helping T cells kill the myeloma cells.

“Bi typically means two, and just know that [this] means that these are bifunctional antibodies, and so they can target two cell surface molecules at the same time,” Blue said. “Typically, it's the CD3 [protein], which is typically on the T cells, and then that CD3 is typically paired with either BCMA [protein] or some other plasma cell target.

“So, that's why the good thing for bispecifics is that if we keep finding more and more targets on the plasma cells, then we can keep having more and more therapies. Because we know that the plasma cells are really the problem, we just have to keep identifying more and more ways to kill them more effectively. We all are working towards getting to that cure.”

A notable example of a bispecific antibody for the treatment of multiple myeloma is Tecvayli (teclistamab), which, based on the findings of the MajesTEC-1 trial, received accelerated approval from the Food and Drug Administration in 2022 for the treatment of adult patients with pretreated, relapsed or refractory multiple myeloma. The agency reported that it was the first BCMA-directed CD3 T-cell engager approved for members of this patient population.

“These [treatments] are reserved for people who are in the relapsed and refractory setting, meaning that after you've seen some of the tried-and-true medicines for multiple myeloma. Now we have these extra therapies that will be used as a way to bring your disease from high, down to low and to get it back into remission, which is always the goal and always the plan,” said Blue. “Right now, unfortunately, they are approved for after you've seen several lines of therapy, but just like anything else, we will imagine that those will likely get pushed further and further earlier in the line of multiple myeloma treatment.”

Blue was among the researchers who, in real-world data presented at the 2023 American Society of Hematology Annual Meeting, showed that Tecvayli had comparable safety and efficacy among patients in clinics as it did in the phase 2 MajesTEC-1 trial.

Findings from MajesTEC-1 and five phase 1 trials such as MagnetisMM-1 and MonumenTAL-1 showed overall response rates (the percentage of patients whose disease responded partially or completely to treatment) ranged from 62% to 81% among patients who had received a median of five to six prior therapies.

“There has been a mantra in multiple myeloma that as you get further and further down the multiple myeloma road, the treatments work less and less and less,” Blue said. “But now we're seeing that’s actually not necessarily true. We still have people who've been exposed to multiple lines of therapy, but we still have medicines that work 50%, 60%, 70% of the time, which is fantastic.”

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