Promising Early Safety Profile of P-BCMA-ALLO1 CAR-T Therapy for Relapsed/Refractory Multiple Myeloma Patients
Dr. Dholaria Bhagirathbhai presents the early safety results of P-BCMA-ALLO1 in relapsed/refractory multiple myeloma patients with measurable disease who have received a proteasome inhibitor (PI), immunomodulatory agent (IMiD) and anti-CD38 monoclonal antibody therapy.
Abstract Title:
Early Safety Results of P-BCMA-ALLO1, a Fully Allogeneic Chimeric Antigen Receptor T-Cell (CAR-T), in Patients with Relapsed / Refractory Multiple Myeloma (RRMM) Presented at ASH 2023
What is the purpose of this trial?
The purpose of this trial is to evaluate the safety and determine the maximum tolerated dose (MTD) of P-BCMA-ALLO1, an innovative allogeneic Chimeric Antigen Receptor T-cell (CAR-T) therapy designed to target B-cell maturation antigen (BCMA). This treatment is tailored for patients with relapsed/refractory multiple myeloma (RRMM) who have previously undergone proteasome inhibitor (PI), immunomodulatory agent (IMiD), and anti-CD38 monoclonal antibody therapy.
P-BCMA-ALLO1 is crafted from healthy donor T-cells using a non-viral transposon-based integration method called the piggyBac® DNA Delivery System. This system introduces a human anti-BCMA VH-based CAR and incorporates an iCas9 safety switch. Notably, the piggyBac® DNA delivery system produces a highly enriched T stem cell memory product.
To enhance safety, the Cas-CLOVER™ Site-Specific Gene Editing System is employed to eliminate endogenous T cell receptor (TCR) expression. This involves knocking out the TCR beta chain 1 gene to prevent graft-vs-host disease (GvHD) and the beta-2 microglobulin gene to reduce Major Histocompatibility Complex (MHC) class I expression, thereby diminishing host-vs-graft responses.
The trial aims to understand the safety profile and determine the optimal dose by assessing dose-limiting toxicity (DLT) in RRMM patients with measurable disease. Additionally, a key secondary objective is to evaluate the anti-myeloma effect of P-BCMA-ALLO1. Exploratory objectives include studying CAR-T related cytokines, serum BCMA levels, and cellular kinetics. The compelling activity demonstrated by P-BCMA-ALLO1 in preclinical models supports the rationale for this critical first-in-human phase I study.
In this video:
Dholaria Bhagirathbhai, MBBS, (Vanderbilt University Medical Center — Nashville, TN) discusses the two objectives of study that uses P-BCMA-ALLO1 in relapsed/refractory multiple myeloma patients with measurable disease. The first aim of the trial was to determine the safety profile of maximum tolerated dose (MTD) of P-BCMA-ALLO1. The second was to evaluate the anti-myeloma effect of P-BCMA-ALLO1.
Conclusion:
Researchers find encouraging results with P-BCMA-ALLO1, a CAR-T therapy created without using viruses, making it a readily available "off-the-shelf" option. This innovative treatment is showing promise in a group of patients with Relapsed/Refractory Multiple Myeloma (RRMM) who have undergone extensive prior treatments. Importantly, P-BCMA-ALLO1 is administered swiftly and is well tolerated, carrying minimal risk of cytokine release syndrome (CRS) and neurotoxicity (ICANS).
These positive findings pave the way for potential advancements in RRMM care, offering a novel approach to treatment. Researchers are committed to sharing the latest updates and insights gained from this trial.
Trial Information: Abstract #3479
Doctor Bio:
Bhagirathbhai Dholaria, MBBS, is an Assistant Professor of Medicine within the Division of Hematology and Oncology at Vanderbilt University Medical Center. His professional expertise lies in malignant hematology and cellular immunotherapies, with a specific emphasis on lymphoid and plasma cell malignancies.
Dr. Dholaria is well-versed in diagnosing and treating advanced hematological malignancies using high-intensity chemotherapy and stem cell transplantation. He actively participates in the management of patients undergoing Chimeric Antigen Receptor (CAR) T-cell therapies through various clinical studies at VUMC. Notably, he contributes to the B cell Lymphoma Panel of the National Comprehensive Cancer Network (NCCN) and has conducted extensive research utilizing international transplant registries to analyze transplant outcomes in acute leukemia patients.
Dr. Dholaria's team has made significant contributions to the field, with their work on stem cell transplantation being featured in multiple published manuscripts. Currently, his research efforts are directed towards enhancing the outcomes of patients undergoing CAR T cell therapy and bi-specific antibody-based therapies.
