BCMA-TARGETED CAR-T CELL THERAPY FOR MULTIPLE MYELOMA

Smart overview of the Invention

Chimeric Antigen Receptor (CAR)-T cell therapy targeting B-cell maturation antigen (BCMA) offers a promising approach for treating multiple myeloma, particularly in patients who have not achieved complete response after initial therapies like stem cell transplantation. The treatment involves administering CAR-T cells that include a BCMA-specific CAR, which consists of an extracellular antigen binding domain, a transmembrane domain, and an intracellular signaling domain. This method aims to achieve minimal residual disease (MRD) negativity and improve clinical outcomes.

Therapeutic Approach

The treatment is designed for patients who have undergone stem cell transplantation and possibly high-dose chemotherapy. The CAR-T cells are administered at doses ranging from 1.0×10⁵ to 5.0×10⁶ cells per kilogram of body weight. Prior to CAR-T therapy, patients may receive induction therapy that includes proteasomal inhibitors or immunomodulatory drugs, as well as lymphodepletion therapy using cyclophosphamide and fludarabine.

Treatment Protocols

The therapy is tailored with options such as autologous stem cell transplantation and the use of specific drugs like lenalidomide post-CAR-T infusion. Lenalidomide dosing varies from 2.5 mg to 15 mg daily and can continue for several cycles, depending on patient response and tolerance. The treatment regimen may include bridging therapies and is adaptable to individual patient needs, ensuring optimal efficacy while minimizing toxicity.

Clinical Outcomes

The method shows effectiveness in achieving MRD negativity, assessed through next generation sequencing or flow cytometry at sensitivities as low as 10⁻⁵. MRD negativity is typically observed within 0.9 to 6.1 months post-treatment, with a median time of about 1.33 months. Response rates vary but can reach up to 80% for MRD negativity at high sensitivity levels.

Response Evaluation

The treatment's success is measured by various response levels, ranging from stringent complete response to minimal response. Initial responses are often seen between 0.9 and 12.5 months after CAR-T cell administration, with median times around 1.30 months for first responses and about 1.89 months for best responses. This approach highlights the potential for significant improvements in patient outcomes through targeted cellular therapies.