Mitigating Risk of Infection While Using BCMA Bispecific Antibodies as Treatment

At the 2024 Great Debates & Updates (GDU) in Hematologic Malignancies meeting in New York, Andrew Yee, MD, Massachusetts General Hospital, Massachusetts, and Harvard Medical School, Massachusetts, speaks about mitigating the risks of infection while using BCMA bispecific antibodies as treatment. 

Transcript:

Hi, my name is Andrew Yee. I'm the clinical director for the Center for Multiple Myeloma at Mass[achusetts] General Hospital, and I'm also an assistant professor of medicine at Harvard Medical School. I'm here today at the Great Debates & Updates [in] Hematological Malignancies [meeting] in New York. 

With BCMA bispecific antibody therapy, there is concern about infection. That is a point that my opponent might try to bring up. I will acknowledge [that] yes, there is a high proportion of infection seen with anti-BCMA and bispecific antibody therapy. One of the points I'm going to make is that you have to think about the context of when these trials were conducted.

Some of the initial studies with these bispecific antibodies were done [at] the height of the COVID-19 pandemic. A lot of the infections from these therapies were due to COVID-19. We know now that, in [the] current time, it's just a different landscape of how we think about [the] COVID-19 infection in terms of availability of vaccines, how almost there's probably universal exposure to COVID-19 or vaccination[s]. The concern for COVID-19 isn't as much as it was back then. So, the rate of infections [is] lower now than before in terms of infectious risk overall, respecting bispecific antibodies with BCMA, and that also is borne out in the real-world data as well. 

A couple of other points [are], as we've had more experience in using BCMA bispecific antibodies, we think more about how [we can] optimize the use. In addition to treating [the] risk of infection, I think there's more attention to using intravenous immunoglobulin to treat hypogammaglobulinemia, as well as also the schedule. Right now, for example, teclistamab is approved in the weekly schedule. But recently, in February, there was a change where you allow for every other week dosing.

We've already started to adopt that in practice, where patients can move from weekly dosing to every other week. That helps, obviously, for patient convenience. But also, it turns out that when you change to every other week dosing, you can decrease [the] risk of infection. That was borne out in one of the clinical trials. 

Also, when I think about BCMA and bispecific [antibodies], I just think about, overall, its excellent tolerability compared to some of the other agents out there I think [that] aside  from the risk of infection patients generally feel quite well on therapy so in addition to having a great response I think patients have a great quality of life. So, I think that's another key feature of what I think about using teclistamab or elranatamab. Compared to some of the other therapies we can use, I think patients in general feel quite well. 

One point it will make as a caveat in terms of when you think about BCMA followed by BCMA is that before I've been mainly talking about patients who relapse after CAR-T and how I'm fine using teclistamab or elranatamab, and I think that's an excellent choice. I think the other way around is a little bit more complicated. There's some early data looking at [the] efficacy of CAR T-cell therapy after prior anti-BCMA bispecific antibody.

Some of the early data suggests that those responses may not be as great compared to BCMA-naive patients. We'll point that out as a note of just something to think about. But, then again, it's a little bit more complicated, as all these topics are complicated. Where, in the patients who have progressive disease after BCMA bispecific [antibodies], I think CAR-T efficacy might be affected. But, there’s also emerging data looking at [how] if you use some BCMA bispecific [antibodies] but not necessarily to progression you maybe can achieve good response with CAR T-cell therapy. 

The theme [is], we're really excited about these bispecific antibodies in CAR T-cell therapies. They're new and used, and as time moves on, we're going to have more experience and more sophistication [in] how we use them, so I can think of how these responses are going to get better as we figure out ways how do we optimize the dosing and the sequencing. All in all, I think we're really excited about how we can apply these therapies in practice. 

Source:

Yee A. Debate- BCMA Therapy Followed by Another BCMA Therapy Is Appropriate – YES. Presented at the Great Debates and Updates in Hematologic Malignancies Meeting; April 5-6, 2024; New York, New York.