Teclistamab, a BCMA-targeted bispecific antibody, continues to show promising results in patients with relapsed/refractory multiple myeloma (R/R MM), particularly those who are triple-class refractory. Data from the MajesTEC-1 trial (NCT03145181, NCT04557098) highlight the drug's efficacy and manageable safety profile in this challenging patient population.
Efficacy in Heavily Pre-treated Patients
The MajesTEC-1 trial, a phase 1/2 open-label study, evaluated teclistamab in patients with R/R MM who had received more than three prior lines of therapy and were triple-class exposed. These patients were also B-cell maturation antigen (BCMA) naive. The treatment involved a step-up dosing regimen of teclistamab at 0.06 and 0.3 mg, followed by a treatment dose of 1.5 mg/kg weekly until disease progression. The primary endpoint was overall response rate (ORR), with key secondary endpoints including duration of response, depth of response, and minimal residual disease (MRD) status.
In this heavily pre-treated population, the ORR was 63%, with 46% achieving a complete remission (CR) or better. The median duration of response was 24 months (95% CI, 17.0-NE) for the overall population and was not reached (95% CI, 26.7-NE) for those achieving CR or better. At 30 months, the duration of remission was 45% overall and 60% for those with CR or better. The median progression-free survival (PFS) was 11 months, and the median overall survival (OS) was 22 months (95% CI, 15.1-29.9).
Safety and Supportive Care
While teclistamab demonstrates impressive efficacy, it is associated with certain adverse events. Cytopenias, including anemia, thrombocytopenia, and neutropenia, are common due to cytokine release and inflammation. Cytokine release syndrome (CRS) occurred in 72% of patients (any grade), with grade 3 to 4 CRS occurring in less than 1%. Infections are also a concern, given the immunosuppressed state of multiple myeloma patients and the hypogammaglobulinemia induced by bispecific antibodies.
To mitigate these risks, supportive care is crucial. This includes the use of growth factors, transfusions, and erythropoiesis-stimulating agents for cytopenias. Prophylaxis for viral infections (e.g., acyclovir for herpes) and Pneumocystis jirovecii pneumonia is recommended. Intravenous immunoglobulin (IVIG) supplementation is also important to prevent infections by addressing hypogammaglobulinemia.
Despite these potential adverse events, discontinuation due to adverse events was only 4.8% (n = 8, 5 due to infection), and dose reduction was used in 0.6% (n = 1), highlighting the manageability of teclistamab with appropriate supportive care.
MRD Assessment
Minimal residual disease (MRD) negativity is increasingly recognized as an important endpoint in multiple myeloma, correlating with prolonged PFS and OS. While MRD assessment methods vary across clinical trials (e.g., next-generation sequencing, polymerase chain reaction, flow cytometry), the Mayo Clinic NGS assay is a preferred method in practice.
Patient Characteristics
The MajesTEC-1 trial included a diverse group of patients, with approximately 15% older than 75 years. A significant proportion had high-risk features, including extramedullary disease (17.0%) and high-risk cytogenetics (25.7%). The study also included a substantial number of patients who were triple refractory (77.6%) and penta-drug refractory (30.3%).
