Bridging to CAR T: Talquetamab's Role in Late-Relapse Myeloma

In an interview with Targeted Oncology, Binod Dhakal, MD, MS, associate professor in the Division of Hematology at the Medical College of Wisconsin, discusses a clinical study on a specific treatment approach for multiple myeloma. The main focus is on the use of talquetamab (Talvey) as a "bridge" therapy before administering CAR T-cell therapy. Dhakal discusses the rationale, design, and objectives of the study.

The context of this study is the treatment of patients with multiple myeloma who have had multiple prior lines of therapy, specifically 4 or more. Both talquetamab, a bispecific antibody, and CAR T-cell therapy are approved for use in this heavily pretreated patient population. Dhakal clarifies that this study is not focused on patients who might be eligible for earlier lines of CAR T-cell therapy, but rather on those with late relapses. The core idea is to see if using talquetamab to control the disease while a patient is preparing for CAR T-cell therapy is a safe and effective strategy.

To investigate this, researchers conducted a retrospective study and looked back at data that had already been collected. The data was gathered from a consortium of centers, including 18 from the US Multiple Myeloma Immunotherapy Consortium and 2 German centers, all of which had experience with this specific talquetamab bridging approach. By pooling the data, the researchers could analyze a larger group of patients.

The primary objective of the study was to assess the feasibility of this approach, with a particular emphasis on safety. The researchers wanted to confirm that using talquetamab as a bridge therapy was safe both during the bridging period and after the subsequent CAR T-cell therapy. The safety endpoints included common side effects associated with both types of treatment, such as cytokine release syndrome (CRS) and emmune effector cell-associated neurotoxicity syndrome (ICANS). They also specifically looked at unique toxicities associated with talquetamab, as well as other potential adverse events that can occur with both bispecific antibodies and CAR T-cell therapies, such as infections, the development of secondary primary malignancies, and cytopenias.

Beyond safety, the study also aimed to evaluate the efficacy of this bridging strategy. This was assessed by looking at the patient's response to the treatment. Specifically, the researchers analyzed the response to talquetamab as a bridge and the subsequent response after the CAR T-cell therapy. The intent was to determine if this treatment sequence could lead to meaningful clinical outcomes. The efficacy end points included standard measures of disease control and survival, such as time to event outcomes, progression-free survival (PFS), overall survival (OS), and non-relapse mortality. The study's design ensures that all patients included had the intent to receive BCMA-targeted CAR T-cell therapies ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma) as the standard of care. This focus on intent to treat is crucial in clinical studies to avoid bias.