PII-021 - EXPOSURE RESPONSE (E-R) RELATIONSHIPS OF LISOCABTAGENE MARALEUCEL (LISO-CEL) IN PATIENTS WITH RELAPSED OR REFRACTORY (R/R) MANTLE CELL LYMPHOMA (MCL)

K. Ogasawara, N. Balasubramanian, J. Cummings, H. Lin, A. Raviele, L. Peng, A. Omidpanah, R. Espinola, A. Kostic; Bristol Myers Squibb.

Background: Liso-cel is an autologous, CD19-directed, 4-1BB chimeric antigen receptor (CAR) T-cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells that has demonstrated considerable efficacy and a manageable safety profile across R/R B-cell malignancies. In the primary analysis of the MCL cohort of TRANSCEND NHL 001 study, liso-cel recently demonstrated a rapid, high rate of durable complete responses and was well tolerated with low incidence of grade ≥3 cytokine release syndrome (CRS), neurological events (NE), and infection in R/R MCL, who received a dose of either 50 or 100 × 10^6 CAR+ T cells. Here we characterize the cellular kinetics (CK) of liso-cel and the E-R relationships for clinical efficacy/safety endpoints in patients with R/R MCL.

Methods: Liso-cel transgene levels in peripheral blood were measured using a validated quantitative polymerase chain reaction assay. Noncompartmental CK parameters such as maximum transgene level (Cmax), time of Cmax (Tmax), and area under the curve for transgene level from 0 to 28 days after liso-cel infusion, were calculated as expansion metrics. The relationships between CK parameters and clinical parameters were assessed by Wilcoxon tests and Cox proportional hazards model.

Results: Liso-cel exhibited a rapid expansion with a median Tmax of 10 days in patients with R/R MCL (N=79). For E-R for efficacy, higher expansion was observed in complete responders than non-complete responders (3.6-fold higher median Cmax, p < 0.05). No apparent relationship was observed between CK parameters and objective response. A ten-fold higher expansion was associated with longer progression-free survival (PFS) and duration of response (DOR) (hazard ratio [95% confidence interval] for Cmax, 0.60 [0.40-0.91] and 0.63 [0.41-0.98], respectively, p < 0.05). For E-R for safety, higher expansion was observed in subjects who had any grade CRS, any grade NE, or grade ≥ 3 NE, as compared to subjects who did not (2.5-fold, 5.8-fold, or 4.9-fold higher median Cmax, respectively, p < 0.05). The frequency of grade ≥3 CRS was too low to assess potential relationships.

Conclusion: In patients with R/R MCL, higher liso-cel expansion was found to be associated with higher complete response rate, longer PFS/DOR, as well as higher incidence of CRS (any grade) and NE (any grade and grade ≥3).