Sequencing Bispecific Agents in a Rapidly Evolving Multiple Myeloma Space

In a conversation with CancerNetwork^® at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH), Ira Zackon, MD, highlighted considerations related to the sequencing of bispecific antibodies along with other anti-cancer therapies in the treatment of patients with multiple myeloma. He spoke about these treatment strategies in the context of a study he presented at the meeting, which detailed real-world use patterns of bispecific antibodies for patients with relapsed/refractory disease in a US community oncology setting.

According to Zackon, a hematologist/oncologist at Albany Medical Center of New York Oncology Hematology, bispecific antibodies are currently indicated for treatment following 4 or more prior lines of therapy, although ongoing trials are evaluating the efficacy of these agents in earlier settings. He posed the question of whether it was more effective to target BCMA using agents like teclistamab-cqyv (Tecvayli) and elranatamab-bcmm (Elrexfio) or use talquetamab-tgvs (Talvey), which is directed towards GPRC5D. Additionally, using bispecific antibodies before or after CAR T-cell therapy may raise the possibility of needing to target alternate proteins depending on the sequencing of these agents.

Transcript:

Currently, in the multiple myeloma space, bispecifics are approved after at least 4 lines of therapy. It’s a later-in-line treatment. Clinical trials are looking at earlier introduction of these therapies.

We still tend to use the other major classes of therapy by the time we get to that late stage. It’s going to be an even more important question [to answer] as these hopefully move to earlier [lines of therapy], as you need to make decisions in sequencing.

Two aspects that we still need to learn about sequencing is that 2 of the bispecifics, teclistamab, and elranatamab, target a protein called BCMA that is rich in myeloma plasma cells. Then talquetamab has a different target [in GPRC5D]....What’s our better target? There are some other BCMA-targeted therapies. For example, CAR T cells in multiple myeloma are targeted to the BCMA protein. We need to learn about the use of bispecifics after CAR T. Or, how effective is CAR T if they’ve had a bispecific in reverse order? Do we target an alternative protein? There’s still a lot to learn because it’s a rapidly evolving space.

Reference

Herms L, Su Z, Paulus J, Zackon I. Real-world utilization of bispecific antibodies for treatment of relapsed/refractory multiple myeloma in the US community oncology setting. Blood. 2024;144(suppl 1):2410. doi:10.1182/blood-2024-208825