Finding the Best Setting for Bispecific T-Cell Engagers in Multiple Myeloma

Shebli Atrash, MD, discussed considerations for optimizing T-cell engager efficacy in an interview with CancerNetwork® following his presentation on T-cell engagers in multiple myeloma that he gave at the 2025 Immune Cell Effector Therapy Conference.

Atrash, medical oncologist at Levine Cancer Institute and clinical associate professor of medicine at Wake Forest University, expressed that T-cell engager effectiveness is variable based on the setting in which it is used. To illustrate this, he explained that using the T-cell engager talquetamab-tgvs (Talvey) prior to chimeric antigen receptor (CAR) T-cell therapy may help reduce the incidence of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS).

On the other hand, he stated that using bispecifics for patients with rapidly progressing disease and high disease burden may not exhibit the same efficacy or clinical benefit for patients, underscoring a need to consider how and when they are used as well as who will most benefit from their use.

In conclusion, Atrash expressed a need in the field to identify why approximately 30% of patients do not respond to treatment with bispecific T-cell engagers, suggesting that it may have to do with the host immune system, fitness, and cancer cell soluble BCMA levels.

Transcript:

Using those bispecific [T-cell] engagers in the right setting is important. For example, utilizing talquetamab, a GPRC5D bispecific antibody, as a pre–CAR T drug to control myeloma prior to administering CAR T has helped us with decreasing CRS and ICANS. [Additionally, regarding] my experience with teclistamab, if it’s used in patients who are rapidly progressing with large disease burden, then it might not provide as much efficacy as it does for other patients. I feel the future directions will be regarding how to use it, when to use it, [and] which population is most fit for those treatments.

Also, we have noticed that when you start the treatment in the first month or two, you get a drop of about 30% in the survival curves, indicating that those patients did not respond to treatment. Predicting who [makes up that] 30% is important, and this has to do with the host immune system, fitness, as well as the cancer cell soluble BCMA levels. Those are the important takeaways.

Reference

Atrash S. Emerging T-cell engagers & novel immunotargets in multiple myeloma. Presented at: 2025 National Immune Cell Effector Therapy Conference; July 26, 2025; Orlando, FL.