The experimental immunotherapy drug teclistamab (Tecvayli) is showing promising results in patients with advanced multiple myeloma who have exhausted multiple lines of treatment. The MajesTEC-1 trial demonstrated that teclistamab induced a significant response in patients with relapsed or refractory multiple myeloma, offering a potential new option for those with limited alternatives. The trial's findings, published in the New England Journal of Medicine, have led to teclistamab's approval in the European Union and anticipation for FDA approval in the United States.
Efficacy in Heavily Pretreated Patients
The MajesTEC-1 trial enrolled 165 adults with relapsed or refractory multiple myeloma who had previously received at least three prior therapies. Half of the participants had undergone five previous lines of treatment, and 82% had a prior stem cell transplant. The results showed that nearly two-thirds of participants experienced at least a partial response to teclistamab, and almost 40% achieved a complete remission. The median time patients lived without their cancer progressing was approximately 11 months, and the responses lasted a median of 18 months. According to Saad Usmani, M.D., chief of the myeloma service at Memorial Sloan Kettering Cancer Center and an investigator on the trial, these responses are impressive compared to other options for heavily pretreated patients, who typically have a survival expectancy of only 8 to 9 months.
Mechanism of Action and Target
Teclistamab is a bispecific antibody that targets BCMA (B-cell maturation antigen) on myeloma cells and CD3 on T cells. By binding to both targets simultaneously, teclistamab brings myeloma cells and T cells together, facilitating the T cells to recognize and destroy the tumor cells. BCMA is a protein commonly found on plasma cells and is often expressed at higher levels on multiple myeloma cells, making it an attractive therapeutic target.
Safety and Side Effects
While teclistamab demonstrated significant efficacy, it is associated with notable side effects. The most common serious side effects observed in the MajesTEC-1 trial were infections and low blood cell counts. Almost all participants (95%) experienced at least one side effect. Cytokine release syndrome, a potentially serious immune reaction, was also observed, though it was mostly mild or moderate and managed with supportive care. To mitigate the risk of severe reactions, patients received two smaller "step-up" doses of teclistamab before the full dose and were monitored in the hospital during the initial doses.
Comparison with CAR T-Cell Therapy
CAR T-cell therapy, another BCMA-targeted treatment for multiple myeloma, has shown high response rates in clinical trials. However, teclistamab offers some potential advantages. According to Dr. Usmani, teclistamab can be initiated more quickly than CAR T-cell therapy, which requires several weeks to manufacture the patient's own T cells. Additionally, teclistamab may be an option for older patients who are not eligible for CAR T-cell therapy based on current criteria. However, teclistamab requires weekly infusions to maintain its effect, while CAR T-cell therapy is a one-time treatment. James Kochenderfer, M.D., a senior investigator in NCI’s Center for Cancer Research, noted that neither CAR T-cells nor teclistamab are likely to cure more than a very small percentage of people with multiple myeloma, so research on better treatments is needed.
Future Directions
Ongoing studies are exploring the use of teclistamab in combination with other drugs for patients with multiple myeloma who have not received multiple prior treatments. Researchers are also investigating the optimal sequencing of teclistamab with other BCMA-targeted therapies, including CAR T-cell therapy. The availability of teclistamab represents an important advancement in the treatment of multiple myeloma, particularly for patients with relapsed or refractory disease.
