Abstract
Idecabtagene vicleucel (ide-cel, ABECMA) is an autologous, B-cell maturation antigen-directed, chimeric antigen receptor (CAR) T-cell therapy, which has demonstrated significantly improved progression-free survival (PFS) and overall response rate (ORR) in patients with triple-class-exposed relapsed/refractory multiple myeloma (TCE RRMM). Here, we characterize cellular expansion of ide-cel in vivo and further evaluate associations between cellular expansion and clinical efficacy and safety endpoints. The exposure parameters of ide-cel were evaluated through non-compartmental analysis methods using the time course data of CAR transgene copy numbers collected from the ide-cel arm of Study KarMMa-3 (NCT03651128). Multivariable regression analyses were conducted between the exposure parameters and clinical responses to characterize relationships between cellular expansion in vivo and clinical outcomes and to evaluate potential effects of covariates on the exposure-response (E-R) relationships. There appears to be lack of a strong association between actual ide-cel dose and cellular expansion at the dose range evaluated in Study KarMMa-3. The multivariable E-R regression models suggest positive relationships between cellular expansion and clinical efficacy and safety endpoints, with higher exposure associated with longer PFS, higher ORR, and higher rates of cytokine release syndrome requiring tocilizumab or corticosteroids. The current analyses do not identify any clinically relevant covariate effects on the E-R relationships. The positive exposure-response relationships were found to be overall similar between KarMMa-3 and a previous study KarMMa. The modeling analyses, paired with clinical data, support extending the dose range from previously approved 300-460 × 10(6) CAR+ T cells to 300-510 × 10(6) CAR+ T cells for TCE RRMM patients.