KEY TAKEAWAYS
- The KarMMa phase II study (NCT03361748) aimed to characterize the exposure-response relationship of ide-cel with critical efficacy endpoints and safety events in patients receiving the target doses.
- Logistic regression models were used to quantify the observed exposure-response trends of ide-cel, and individual covariates were included in a stepwise regression analysis to modify the models.
- The study results indicated a positive benefit-risk assessment for the range of ide-cel exposures associated with the target dose range, with higher response rates and more safety events of cytokine release syndrome requiring tocilizumab or corticosteroids being associated with higher exposures.
The B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, Idecabtagene vicleucel (ide-cel; bb2121), has been approved to treat heavily pretreated relapsed and refractory multiple myeloma patients. An analysis investigated the relationship between ide-cel exposure, critical efficacy endpoints, and safety events. Exposure data from 127 patients treated with ide-cel doses of 150, 300, or 450 × 106 CAR+ T cells were evaluated using non-compartmental methods to calculate exposure metrics, including maximum transgene level and area under the curve of the transgene level from 0 to 28 days.
Logistic regression models were used to quantify observed exposure-response trends, and individual covariates were included in a stepwise regression analysis. The analysis revealed that higher exposure levels were associated with higher overall and complete response rates. Model-based evaluations also identified female sex and baseline serum monoclonal protein levels as predictive of higher objective and total response rates. The analysis also revealed exposure-response relationships for cytokine release syndrome safety events requiring tocilizumab or corticosteroids. The study results indicated the exposure-response models were used to quantify the ide-cel dose-response, which indicated a positive benefit-risk assessment for the range of ide-cel exposures associated with the target dose range of 150-450 × 106 CAR+ T cells.
Source: https://pubmed.ncbi.nlm.nih.gov/36794354/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03361748/
Connarn JN, Witjes H, van Zutphen-van Geffen M, de Greef R, Campbell TB, Hege K, Zhou S, Lamba M. Characterizing the exposure-response relationship of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma. CPT Pharmacometrics Syst Pharmacol. 2023 Feb 15. doi 10.1002/psp4.12922. Epub ahead of print. PMID: 36794354.
