Comparing Teclistamab Trial Designs for Early Relapsed Multiple Myeloma

Roberto Mina, MD, associate professor of hematology at the Winship Cancer Institute at Emory University, highlighted the pivotal role of B-cell maturation antigen (BCMA) targeting therapies. Mina noted that while several trials, including those involving chimeric antigen receptor (CAR) T cells and antibody-drug conjugates (ADCs), have investigated these therapies, significant nuances exist in patient populations and study designs that clinicians must navigate.

Key Differences in Clinical Trial Design

The primary distinction between the MajesTEC-3 (NCT05083169) and MajesTEC-9 (NCT05572515) trials lies in the therapeutic combinations utilized. In the MajesTEC-9 study, teclistamab is administered as a monotherapy, focusing on its independent efficacy. Conversely, MajesTEC-3 explores the synergistic potential of teclistamab in combination with daratumumab (Darzalex), an anti-CD38 monoclonal antibody.

Beyond the drug combinations, the trials vary based on the prior treatment history of the enrolled patients. Both trials enrolled patients with 1 to 3 prior lines of therapy, thus including patients after their first relapse. These differences include varying levels of prior treatment with immunomodulatory drugs, differences in whether patients had previously progressed on therapies like daratumumab or isatuximab (Sarclisa), heterogeneity in patient age, frailty, and cytogenetic risk profiles across the different cohorts. As anti-CD38 antibodies have been introduced more recently, some patients may not have received them whereas those treated more recently may be refractory to them.

Clinical Implications and the Future of Care

Mina emphasized that both the MajesTEC trials and various CAR T-cell studies have yielded robust results, confirming that targeting BCMA is highly effective in early lines of therapy—potentially as early as the second line. Both progression-free survival (PFS) and overall survival (OS) data suggest that these platforms are transforming the standard of care.

Ultimately, the existence of multiple BCMA-targeting platforms—bispecific antibodies, CAR T-cells, and ADCs—provides clinicians with a complementary toolkit. Because these options differ in terms of logistics, such as off-the-shelf vs personalized, as well as access, and safety profiles such as the timing and severity of cytokine release syndrome, physicians can tailor treatments based on patient preference and clinical status.