PII-017 - CHARACTERIZING CELLULAR KINETICS OF IDECABTAGENE VICLEUCEL IN PATIENTS WITH TRIPLE-CLASS-EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA.

F. Wu¹, X. Zheng¹, J. Burnett², J. Zhou¹, Y. Chen¹, A. Caia³, M. Cook¹, A. Kondic¹, M. Lamba⁴; 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 cellular kinetics (interchangeably with pharmacokinetics or PK) 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 PK analysis population included subjects (N=224) who have measurable transgene levels post ide-cel treatment from the ide-cel arm of Study KarMMa-3 (NCT03651128) as of the data cutoff date of 01-Mar-2022. The PK parameters of ide-cel were evaluated using the time course data of droplet digital polymerase chain reaction (ddPCR)-quantified CAR transgene copy numbers through non-compartmental analysis (NCA) methods. A multivariable linear regression model was developed to evaluate dose-exposure relationship and potential covariate effects based on Bayesian Information criteria (BIC).

Results: The analyses suggested similar exposures between the dose categories of 300 to 460 ×10^6 and > 460 to 540 ×10^6 CAR+ T cells and considerable inter-subject PK variability across all doses (> 200% Geometric CV%). Further multivariable regression modeling analyses suggested a positive although statistically non-significant relationship between actual dose and exposure represented by area under curve of CAR transgene levels from 0 to 28 days (AUC0-28D). The regression analyses also identified significant covariates for exposure including baseline IL-15, presence of extramedullary plasmacytoma, post-infusion antidrug antibody, lentiviral vector type, and body weight.

Conclusion: The PK characterization analyses suggested that robust cell expansion was achieved at doses above 300×10^6 CAR+ T cells in TCE RRMM patients enrolled in KarMMa-3. Whilst statistically significant effects were identified for some covariates, their impact on cellular expansion is modest and not clinically relevant.