Bispecifics Under Development for The Treatment of R/R Multiple Myeloma

Dr Shaji Kumar highlights bispecifics under development and how BCMA-targeting therapies impact patient selection for the treatment of R/R multiple myeloma.


Shaji Kumar, MD: Unfortunately, myeloma continues to relapse. Even with the teclistamab or the CAR [chimeric antigen receptor] T cells, we are still looking at patients who continue to relapse. We need additional therapies for patients with myeloma. Thankfully, there are several bispecific antibodies in development that are not only targeting BCMA [B-cell maturation antigen] but also other antigens, such as FcRH5 in the case of cevostamab or GPRC5D in the case of talquetamab. All these bispecific antibodies, irrespective of the target, appear to have an activity that’s quite similar with almost two-thirds of the patients getting some response. Again, the responses are reasonably durable, lasting for upward of a year for most.

What we must understand over the next few years is how we sequence these different bispecific antibodies. Do we use different bispecific antibodies based on the target? Do we use them in sequence, or do we go after the same target but using different platforms such as CAR T-cell therapy, bispecific antibodies, or antibody-drug conjugates? Much needs to be learned, particularly in the context of bispecific. There are clinical trials looking at combinations, particularly with monoclonal antibodies, which might be the way we end up using bispecific in the future, in combination and potentially for a limited duration of time.

Fortunately, we have several platforms we can use to target the BCMA. We know it’s a well-validated target antigen in myeloma. A lot of it is determined by the availability of therapies while we have an antibody-drug conjugate like belantamab approved, as well as teclistamab and 2 CAR T cells approved for BCMA. A lot of the treatment choices are often driven by availability, particularly that of the CAR T. There’s limited availability for CAR T, and that is often preferred in the setting of a patient like whom we just talked about.

Unfortunately, a large proportion of those patients may not be able to access CAR T, either because we don’t have available slots or because they are in a smaller community practice without cellular therapy facilities. For those patients, bispecific antibodies are the best option, primarily in the sense of the good response rate we have seen.

If that is not an option, then certainly BCMA-targeted antibody-drug conjugates, such as belantamab, would be of value. There are phase 3 trials looking at combining belantamab with other standard-of-care agents, such as protostome inhibitors and immunomodulatory drugs. Hopefully, those trials will also provide some guidance in terms of when to use a specific combination, whether it be an antibody-drug conjugate or bispecific antibody.

Transcript edited for clarity.

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