PII-101 - CHARACTERIZING EXPOSURE-RESPONSE RELATIONSHIPS OF IDECABTAGENE VICLEUCEL IN PATIENTS WITH TRIPLE-CLASS-EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA.

J. Zhou¹, J. Burnett², X. Zheng¹, Y. Chen¹, A. Caia³, M. Cook¹, A. Kondic¹, M. Lamba⁴, F. Wu¹; ¹Bristol Myers Squibb, ²Bristol Myers Squibb, 556 Morris Ave, United States, ³Bristol Myers Squibb, , United States, ⁴Bristol Myers Squibb, Summit, NJ, United States.

Background: Ide-cel (Idecabtagene Vicleucel) is a genetically modified autologous T cell immunotherapy product, which has demonstrated significantly improved progression-free survival and overall response rate in patients with Triple-Class–Exposed Relapsed/Refractory Multiple Myeloma (TCE RRMM). The current analyses aim to explore the exposure-response (E-R) relationship for key efficacy and safety endpoints in patients with TCE RRMM who had received 2 to 4 prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

Methods: The E-R analysis population included subjects (N=220) who have evaluable PK parameters from the ide-cel arm of Study KarMMa-3 (NCT03651128). The relationship between ide-cel exposure (represented by area under the curve of CAR transgene levels from 0 to 28 days or AUC0-28D) and progression free survival was described by a Cox Proportional Hazard model, the relationship between AUC0-28D and overall response rate (ORR) was described by a sigmoid Emax logistic regression model, and the relationship between expansion rate and cytokine release syndrome requiring treatment of tocilizumab/siltuximab (tCRS) or corticosteroids (sCRS) was described by linear logistic regression models. The potential covariate effects on the E-R relationship were assessed using multivariable regression methods based on Bayesian Information criteria (BIC).

Results: Apparent E-R relationships were observed for PFS, ORR, tCRS, and sCRS across exposure associated with actual doses ranging from 175 to 529×106 CAR+ T cells. The E-R analyses further suggested the higher risk of disease progression (i.e., shorter PFS) in subjects with prior triple refractory history status, whereas the lower risk of disease progression (i.e., longer PFS) in subjects with lower disease burden measured by baseline soluble BCMA. The analysis also suggested that presence of extramedullary plasmacytoma was associated with lower odds of response. No significant or clinically relevant covariates were identified in E-R relationship for tCRS and sCRS.

Conclusion: Overall, the E-R analyses suggested positive therapeutic benefit at exposure of ide-cel at doses above 300×106 CAR+ T cells in TCE RRMM patients who had received 2 to 4 prior lines of therapy.