Nina Shah and other experts discuss the use of CAR-T therapy in multiple myeloma, highlighting the impressive results of the CRB-401 study and the significance of deep responses. They also explore the improvements in quality of life with IDESL treatment, challenges related to determining treatment lines, and the approval of the first cell-based gene therapy. The podcast covers the safety, efficacy, and ongoing studies of Sulta Cell and the use of T-cell engaging antibodies for multiple myeloma, including factors to consider when selecting therapy.
Idocel (BB-2121) has shown promising results in trials, with FDA approval as the first cell-based gene therapy for multiple myeloma.
Bi-specific T-cell engagers (BiTEs) offer unique advantages such as off-the-shelf availability and shorter treatment timelines for multiple myeloma patients.
Deep dives
Idocel (BB-2121) as a BCMA CAR-T cell therapy for multiple myeloma
Idocel, also known as BB-2121, is an investigational chimeric antigen receptor T-cell therapy that targets B-cell maturation antigen (BCMA) in patients with multiple myeloma. The therapy has shown promising overall response rates and median progression-free survival in phase one and two trials. The updated data from the CRB-401 study revealed a median progression-free survival of 8.8 months and an overall survival of 34.2 months. Based on these positive results, Idocel has received FDA approval as the first cell-based gene therapy for multiple myeloma.
Seldecisil as an allogeneic BCMA CAR-T therapy for multiple myeloma
Seldecisil is an allogeneic BCMA CAR-T therapy that is currently being evaluated in a phase one study for relapsed or refractory multiple myeloma. Early data shows that Seldecisil has significant anti-tumor activity with an overall response rate of 69% and a very good partial response rate of 55% at the recommended phase two dose. The therapy has shown manageable safety profile with low-grade cytokine release syndrome and reversible neurotoxicity. Further studies are ongoing to evaluate the long-term outcomes, retreatment feasibility, and comparison with other treatments.
Bi-specific T-cell engagers (BiTEs) in multiple myeloma
Bi-specific T-cell engagers (BiTEs) are another promising approach for multiple myeloma treatment. These molecules target both BCMA and CD3, engaging T-cells to eliminate myeloma cells. Clinical trials with BCMA-targeting BiTEs, such as AMG420 and Takedolizumab, have shown significant anti-tumor activity, with response rates ranging from 40-70% and durable complete responses. While comparison between BiTEs and CAR-T therapy is challenging, BiTEs offer unique advantages such as off-the-shelf availability and shorter treatment timelines. Further research is needed to determine the optimal application of BiTEs in different patient populations.
Comparison of BiTEs and CAR-T therapy for multiple myeloma
Both Bi-specific T-cell engagers (BiTEs) and chimeric antigen receptor T-cell (CAR-T) therapy show promise in the treatment of multiple myeloma. Efficacy of these therapies is still being evaluated, and factors such as disease morbidity, risk assessment, treatment history, age, and comorbidities need to be considered when selecting the appropriate therapy. CAR-T therapy requires a longer manufacturing time and specialized centers, making it more suitable for patients with aggressive disease and younger age. On the other hand, BiTEs offer off-the-shelf availability and may be better suited for elderly patients or those with specific comorbidities. Familiar and social support also play a role in treatment selection. Further research is needed to determine the long-term outcomes and predictors of response for both BiTEs and CAR-T therapy in multiple myeloma.
The treatment of multiple myeloma is a rapidly evolving field with advances in the understanding of myeloma disease biology contributing to the development of novel targeted therapies. Recently, there has been a rapid increase in the number of chimeric antigen receptor (CAR) T-cell therapies being trialed for patients with multiple myeloma, and in March 2021, idecabtagene vicleucel became the first CAR-T therapy to receive FDA approval for the treatment of myeloma.
In this podcast, Nina Shah of the University of California San Francisco, CA; Saad Usmani of the Levine Cancer Institute, NC; Sham Mailankody of the Memorial Sloan Kettering Cancer Centre, NY; Adam Cohen of the Abramson Cancer Centre, PA; and Maria-Victoria Mateos of the University Hospital of Salamanca, Spain, discuss the use of CAR-T therapy in patients with multiple myeloma.