In an interview with Targeted Oncology, Binod Dhakal, MD, MS, associate professor of medicine at the Medical College of Wisconsin, Division of Hematology, discusses a study investigating the use of talquetamab (Talvey), a bispecific antibody, as bridging therapy before BCMA-directed CAR T-cell therapy.
This study provides crucial insights into the use of talquetamab as a bridging therapy for patients with multiple myeloma who are candidates for CAR T-cell therapy. The data suggest that talquetamab can be an effective and safe way to control the disease before CAR T-cell infusion. This approach is particularly valuable for patients whose high disease burden might otherwise compromise their eligibility or safety for CAR T-cell therapy.
The core finding is that talquetamab can act as a bridge, allowing patients to achieve better disease control, which in turn can lead to more favorable outcomes with subsequent CAR T-cell therapy. The study demonstrates that this sequential targeting—first with talquetamab, which targets GPRC5D, and then with BCMA-targeting CAR T cells is a promising strategy. By hitting 2 different antigens, this approach aims to eradicate as much of the myeloma as possible, potentially leading to more durable responses.
When considering a patient for this bridging strategy, it’s crucial to assess their eligibility for both bispecific antibody therapy (like talquetamab) and CAR T-cell therapy. While there can be some overlap, the eligibility criteria aren’t always identical. The ideal candidate for this bridging approach is a patient who is clinically eligible for CAR T-cell therapy but currently has a high disease burden that may be negatively impacting their overall health, such as their performance status. In such cases, using talquetamab to quickly reduce the tumor load can make the patient a safer and more viable candidate for the intensive CAR T-cell procedure. However, the benefits of this approach for patients with a lower disease burden who are already good candidates for CAR T-cell therapy need further prospective investigation.
One of the most intriguing aspects of the study is its findings on the safety profile of this sequential treatment. The data from 119 patients, with 98 receiving the therapy, showed no delayed toxicities, such as Parkinsonism or Guillain-Barré syndrome, in a follow-up of at least 7 months. This is a significant observation, especially considering the study’s global nature, involving 18 centers in the US and 2 in Germany.
This raises a critical question: Does the use of talquetamab as a bridging therapy actually have a protective effect, creating a more favorable safety profile for the subsequent CAR T-cell therapy?
Further research is needed to explore this possibility. While the current data are encouraging, it’s unclear whether the lack of severe delayed toxicities is a genuine effect of the treatment sequence or simply a result of chance. A deeper investigation into how this bridging strategy impacts the safety and efficacy of CAR T-cell therapy is essential. The hope is that this sequential, dual-antigen targeting approach not only enhances efficacy by eradicating more cancer cells but also mitigates some of the well-known adverse events associated with CAR T-cell therapy, ultimately improving the patient’s overall outcome and quality of life.