“The impossible exists only until we find a way to make it possible.”

Mike Horn

Emily Whitehead was five years old when she was diagnosed with acute lymphoblastic leukemia (ALL). After being treated with chemotherapy for two years, she experienced a failure of therapy which leads to remission in most children. With refractory disease, Emily was the first child to undergo an experimental chimeric antigen receptor (CAR) T-cell therapy and is now a healthy 16-year-old. This experimental CAR -T therapy is now a successful treatment for ALL.

Data presented in New Orleans at the 64th American Society of Hematology’s (ASH) Annual Meeting outlined information about the treatment of relapsed refractory multiple myeloma (RRMM) by various modalities. T cells genetically engineered to express chimeric antigen receptors have some promise in treating relapsed refractory multiple myeloma (RRMM). New strategies have been designed to improve the safety and efficacy of CAR-T cells. Toxicities can now be mitigated to make the procedure safer and more successful. Citacabtagene autoleucel (cilta cel) and idecabtagene vicleucel (ide-cel) are two currently approved CAR T-cell therapies
available with others in development. This has resulted in remission in patients with advanced disease including extramedullary involvement, although the duration of the remission is yet to be determined. So far, CAR T-cell therapy has not resulted in a cure for multiple myeloma.

Other options for treating relapsed refractory multiple myeloma includes T-cell-based immunotherapy known as bispecific T cell engagers (BsAbs). The engagers are constructed to bind a monoclonal antibody to a T cell receptor with the engager binding to the myeloma cell and resulting in cell death. Talquetamab, being the first bispecific to be approved by the FDA with others being evaluated for treating RRMM. These include elranatamab, alnuctamab and RG62349 (currently unnamed). These bispecifics can be taken off the shelf and do not require the complicated—and time consuming—process of engineering the T cell, which would make them more available to myeloma patients with refractory disease.

Until we have a cure for multiple myeloma, the advances in these therapies have been shown to prolong the survival of patients employing greater treatment options for refractory disease.

However, it is important that the best combinations of drugs be given at the right time for a good outcome. The evaluation of cytogenetics can also lead to individualized precision therapies with specific drug combinations.

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