Breaking Down Bispecific Antibodies and Their Shift to Earlier Lines of Treatment

Bispecific antibodies — a type of immunotherapy that brings immune cells into close proximity with cancer cells — are poised to move into earlier lines of treatment for patients with multiple myeloma. This shift is based on findings from recent clinical trials such as MajesTEC-3 and MajesTEC-9, both of which evaluated the use of Tecvayli (teclistamab-cqyv). As part of the “Speaking Out” video series, CURE sat down with Dr. Joseph Mikhael, chief medical officer of the International Myeloma Foundation, to discuss this paradigm shift and what it could mean for patients with multiple myeloma.

CURE: New data show that bispecific antibodies are now moving into the second line of treatment. How does having these powerful tools available at the first sign of relapse change long-term outlooks for patients?

Mikhael: We’ve demonstrated in the past when we have great therapies for myeloma, when we introduce them earlier in the disease course, they have a greater impact, because when patients are treated earlier, their disease is less refractory. It has less time to become more malignant, as it were, and so treatments can give people a deeper and a more durable response.

There’s no doubt that these bispecific antibodies, by the way that they work and the way they engage a patient’s own immune system, are very effective, and they’ve been very effective after four prior lines of therapy. We know that they can now be even more effective when given in the earlier phase and often given in combination, whereas they are initially given as just a single agent.

I really think this is going to open many more opportunities for our patients and the chance to have them achieve a deeper and a more durable response, even in that early-phase disease.

Unlike chimeric antigen receptor (CAR)-T cell therapies, these don’t require weeks of manufacturing. For a patient living far from a major city or a major cancer center, how do bispecifics make academic-level care more accessible in their local clinic?

Access to care is so fundamental in cancer, in general, and specifically in multiple myeloma. And although we know CAR-T cell therapy is a very effective therapy, a lot of patients simply cannot access it geographically and for other reasons. Being able to bring that same technology of immunotherapy, of engaging someone’s own immune system, right to them is, I think, a particularly important aspect of bispecific antibodies.

As we’re learning more about them, as we’re using them more, we’re finding that we can give these drugs more and more in the community. We can manage the side effects. Fewer and fewer patients all the time are needing to be admitted to hospital for these therapies, and so it can be delivered closer to home. And to me, that’s fundamental. Because, somewhere between 75% and 80% of all patients with myeloma are treated in the community, as it were, not connected to an academic center.

And so, we want to ensure that these great therapies that we have are accessible to all.

FDA updates now allow for less frequent dosing, every two weeks. How are we improving quality of life by reducing the time patients spend in the infusion chair?

I say it all the time: I don’t treat myeloma; I treat people. And we really have to look through that filter. It’s fundamental. I don’t just look at plasma cells. I look at the whole of the person. And although we want to give patients the best therapy possible to tackle their myeloma, we want to ensure that they can maintain their quality of life, and we’re learning more about that sweet spot when it comes to bispecific antibodies. In the earliest days, we gave them every week indefinitely.

Although it was very effective, often, it led to a lot of infections, a lot of extra visits to the clinic. And as you noted, it becomes very burdensome for our patients. So now, as we’re seeing how effective these therapies are, we’ve learned that we can back down to every other week after a few doses, and sometimes we’re even backing down to once a month after about six to nine months.

Furthermore, we’re now doing studies looking at the opportunity to stop therapy on certain patients, in particular, somewhere between that 12- to 18-month realm. Sometimes less is more as we care for our patients to get that deep and durable response but allow them less frequent visits, less likelihood of having infections, so that they can live the lives that they want to lead.

This transcript was edited for clarity and conciseness.

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