Elranatamab, a BCMAxCD3 Bispecific Antibody, Demonstrates Effectiveness in Relapsed Myeloma Post-BCMA CAR-T Therapy 

Dan Sherbenou, MD, PhD, discusses an elranatamab trial that aims to contribute vital insights into optimizing the sequencing of BCMA therapies and maximizing benefits for patients at different stages of multiple myeloma.  

Abstract Title:

BCMAxCD3 Bispecific Antibody Elranatamab Is Effective in Patient Myeloma Relapsed after BCMA CAR-T Presented at ASH 2023

What is the purpose of this trial?   

In recent years, groundbreaking therapies targeting the BCMA protein have revolutionized the treatment landscape for patients with relapsed refractory multiple myeloma (RRMM). These therapies, including CAR-Ts and bispecific T-cell engaging antibodies (bsAbs), have shown remarkable effectiveness in late-stage, heavily treated patients. Now, researchers are investigating whether initiating these therapies earlier in the disease progression can yield even better outcomes. 

As the availability of BCMA-targeted agents has rapidly expanded, a critical knowledge gap exists on how to sequence these therapies to optimize patient benefits. This trial aims to address this gap by exploring whether prior exposure to BCMA agents impacts the efficacy of BCMA-targeted re-treatment. 

The approach involves utilizing Myeloma Drug Sensitivity Testing (My-DST) to assess the effectiveness of the anti-BCMA bsAb elranatamab across different disease stages – from initial diagnosis to the post-CAR-T setting. The study employs primary multiple myeloma samples, including patients' own T cells, to provide a comprehensive understanding of the therapy's impact. 

Methods involve obtaining bone marrow and peripheral blood samples from patients with their informed consent and Institutional Review Board approval. These samples are then subjected to My-DST, wherein mononuclear cells are exposed to elranatamab, and the multiple myeloma survival is analyzed using flow cytometry. The study also compares the efficacy of patient-derived T cells from various timepoints and against healthy donors, shedding light on the therapy's broader applicability. 

In this video: 

Dan Sherbenou, MD, PhD (UCHealth Blood Disorders and Cell Therapies Center - Anschutz Medical Campus —Aurora, CO) discusses an elranatamab trial that aims to contribute vital insights into optimizing the sequencing of BCMA therapies and maximizing benefits for patients at different stages of multiple myeloma. 

Conclusion: 

This study demonstrates the effectiveness of Myeloma Drug Sensitivity Testing (My-DST) as a valuable tool in identifying drug resistance to bispecific antibodies, especially when using ex vivo cultures that incorporate the patients' own T cells. The findings from this research strongly indicate that resistance to bispecific antibodies is predominantly linked to the health or quantity of T cells, rather than low BCMA expression.   

These results provide a promising foundation for considering BCMA-targeted re-treatment in patients with sufficient T cell health. The focus on T-cell factors, rather than BCMA expression, suggests a new avenue for optimizing treatment strategies.   

Future investigations will delve deeper into understanding the critical elements of T-cell health, with an emphasis on expanding the sample size. This continued exploration aims to refine our understanding and provide more comprehensive insights into the nuances of bispecific antibody resistance. 

The potential of My-DST as a precision medicine tool is noteworthy, as it holds promise in guiding the treatment of bispecific antibodies. Moreover, the findings suggest that My-DST can play a crucial role in informing the sequencing of bispecific antibodies alongside CAR-T therapies.  

Trial Information: Abstract #4684 (https://ash.confex.com/ash/2023/webprogram/Paper187385.html) 

Doctor Bio: 

Daniel Sherbenou, MD, PhD, is an Associate Professor of Medicine at the University of Colorado, where he is the Director of the Plasma Cell Disorder Program. His professional life is dedicated to treatment and research of multiple myeloma, with a focus on the development of improved treatment approaches. In clinical care, he takes pride in empowering patients with the care team, tools and knowledge to fight their disease and live their best life. As a faculty member in Hematology, Dr. Sherbenou oversees a translational research laboratory group focused on personalized medicine, drug development and understanding how drug resistance occurs and what approaches can be taken to combat it.