Myeloma Treatment: The STEM Trial Phase II Study on Cevostamab Consolidation After BCMA CAR T-Cell Therapy 

Dr. Adam D. Cohen discusses a novel approach using Cevostamab, a bispecific antibody that targets the antigen FcRH5. The aim of the study is to use Cevostamab along with CAR T-cell therapy to achieve sustained minimal residual disease negativity (MRD-). 

Abstract title:

Sequential T-Cell Engagement for Myeloma (“STEM”) Trial: A Phase II Study of Cevostamab Consolidation Following BCMA CAR T Cell Therapy Presented at ASH 2023   

What is the purpose of this trial?  

In this trial, researchers aim to enhance the effectiveness of CAR T-cell therapy for patients with relapsed or refractory multiple myeloma (RRMM). Current CAR T therapies, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have shown remarkable results but are not curative, especially in late-line patients with complete remission. Researchers suspect that issues like CAR T-cell persistence and resistance mechanisms, such as BCMA-low or -negative tumor cells, contribute to the lack of a cure. 

To address this, researchers are testing a novel approach using cevostamab, a bispecific antibody that targets a different antigen called FcRH5. This antigen is present on myeloma cells independently of BCMA expression. The hypothesis is that combining cevostamab with BCMA CAR T-cell therapy could rejuvenate the persisting CAR+ T cells against remaining BCMA+ tumor cells. Simultaneously, it may activate the body's natural T cells against FcRH5+ and BCMA-low/negative tumor cells. The goal is to improve the rates of sustained minimal residual disease (MRD)-negativity and the lasting effectiveness of the treatment.  

In this video: 

Adam D. Cohen, MD, (University of Pennsylvania — Philadelphia, PA) sheds light on a study that looks at the therapy of cevostamab, a bispecific antibody that targets the antigen FcRH5. The aim of the study is to use cevostamab along with CAR T-cell therapy to achieve sustained minimal residual disease negativity (MRD-). 

Conclusion: 

From the abstract: “This phase II study is exploring the efficacy, safety, and feasibility of cevostamab consolidation following BCMA-directed CAR T-cell therapy for relapsed/refractory multiple myeloma (RRMM), with the goal of sequential T-cell engagement against 2 different antigens to eliminate residual disease. Accrual started in July 2023.” 

Trial information: Abstract #3389 (https://ash.confex.com/ash/2023/webprogram/Paper187409.html) 

Doctor bio: 

Adam Cohen, MD, completed his medical degree and internal medicine training at the University of Pennsylvania, followed by a fellowship in hematology/medical oncology at Memorial Sloan-Kettering Cancer Center in New York. 

Board certified in internal medicine, medical oncology, and hematology, Dr. Cohen is an active member of several esteemed professional societies, including the American Society of Hematology, the American Society of Clinical Oncology, the American Association for Cancer Research, and the International Myeloma Society. Within the University of Pennsylvania, he serves as the Director of Myeloma Immunotherapy and contributes as a member of the Clinical Trial Scientific Review and Monitoring Committee. 

As a recognized authority in the field, Dr. Cohen frequently shares his expertise as an invited lecturer. He has authored numerous original articles, book chapters, and reviews covering topics such as DNA vaccines, tumor immunity, multiple myeloma, amyloidosis, and stem cell transplant. Dr. Cohen has also played a vital role as an ad hoc reviewer for reputable journals, including Annals of Oncology, Cytotherapy, Journal of Translational Medicine, Blood, Amyloid, and Clinical Cancer Research. 

His contributions to the field have been acknowledged with accolades such as inclusion in Best Doctors in America in 2016, America's Top Doctors in 2017, and consecutive recognitions in Philadelphia magazine's annual Top Docs issues from 2018 to 2020.