Optimal Use of Bispecific Antibodies for Multiple Myeloma Treatment

At the 2023 Lymphoma, Leukemia & Myeloma Congress in New York, New York, Ajai Chari, MD, University of California – San Francisco, San Francisco, California, discusses the role of bispecific antibodies in the treatment of patients with multiple myeloma, particularly highlighting when they should be implemented into the treatment regimen. 

Transcript:

Hi, my name is Ajai Chari. I’m a professor of clinical medicine and the director of the myeloma program at the University of California, San Francisco. 

Bispecifics are showing amazing responses in myeloma. We’re looking at 60 to 70% responses in heavily-treated patients. When you see that, of course the question is can we move them up earlier? I think the ability of a product to move up earlier is not just efficacy, but safety. 

With the [B-cell maturation antigen] (BCMA) bispecifics, we’re seeing, as a class, serious infections, as high as 55%, Grades 3 and 4, with the most mature follow-up of 23 months. Also, we’re seeing deaths, not due to progression, across all these BCMA bispecifics. I think that gives great pause for the ability of these drugs to move up earlier. I think if we’re going to do BCMA bispecifics, it’s going to be with [Intravenous immunoglobulin] (IVIg), which has shown the benefit of reducing those infections, and maybe looking at the dose, the schedule, and the duration.

With the non-BCMA, with talquetamab, for example, data look[s] really good. We don’t see those deaths. We don’t see those infections. There are other non-hem[atologic] toxicities like dysgeusia [and] palmar-plantar peeling, but interestingly, preliminary data suggests that that may be correlated to efficacy, and those [adverse events] (AEs) are also correlated to response. 

So, it’s possible that we may be able to reduce the dose in patients who are having these Aes, especially when you do combination therapies. We’ve seen data with dara[tumomab] and teclistamab showing [progression-free survival] (PFS) of 19 to 20 months, which is incredible for an off-the-shelf product, without any additive toxicity.
I think the [G protein–coupled receptor, class C] (GPRC5D)s may be [easier] to move, and [Fc receptor-homolog 5] (FcRH5), of course, we needed the data to be more mature and get approval, but that also looks really exciting. 

The final thing I would say would be, right now, we don't have data for these, but I think currently, if a patient's relapsing early or high risk, we really should be putting people on clinical trials to better understand whether this might be the right strategy moving forward.

Source: 

Chari A. Maintenance therapy: Should CD38 ab or bispecifics be incorporated? Does MRD inform type or duration maintenance? Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-21, 2023. New York, NY