Teclistamab Response- and Relapse-Related Immune Correlates in the MajesTEC-1 China Cohort

Teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, demonstrated deep responses and manageable safety in the pivotal MajesTEC-1 study in heavily pretreated relapsed/refractory multiple myeloma (RRMM). Similar efficacy and safety were observed in a separate MajesTEC-1 China cohort (n = 26). In the pivotal cohort, teclistamab response correlated with immune fitness. Here, we evaluated baseline and longitudinal immune profiles in the China cohort to identify immune drivers and potential biomarkers associated with teclistamab response/relapse.

Patients with ≥ 3 prior lines of therapy and triple-class exposed RRMM received teclistamab 1.5 mg/kg weekly after step-up dosing; patients could switch to less frequent dosing with sustained complete response or better.

T-cell redistribution, T-cell activation, and cytokine induction were observed following treatment. Responders had higher baseline CD4⁺ T-cell levels and CD4:CD8 ratios. Lower baseline tumor necrosis factor-α (TNF-α), interleukin (IL)-8, and serum-soluble BCMA levels were associated with response and longer progression-free survival (PFS). Greater T-cell activation in early cycles, assessed by CD38 and programmed death-1 (PD-1), was associated with response. Early induction of IL-10 and IL-2 receptor-α, also indicative of T-cell activation, was associated with response and longer PFS. In patients who relapsed, CD38 and PD-1 expression/coexpression on T-cells remained elevated at relapse versus baseline, consistent with potential T-cell dysfunction.

Greater baseline immune fitness, increased early T-cell activation, and lower inflammation/tumor burden were associated with teclistamab response and longer PFS, while T-cell dysfunction was implicated in relapse. These findings align with teclistamab's mechanism of action and pivotal cohort results.