Impact of pre-lymphodepletion (pre LD) and day 30 (M1) immune cell counts on outcomes of CAR T therapy in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL).

7032 Background: The impact of immune cell counts pre LD and during immune reconstitution on CAR T therapy outcomes is poorly understood. We investigated the association between CD4, CD8 and NK cell counts and CAR T therapy outcomes in patients with LBCL. Methods: Retrospective study of R/R LBCL patients who received CAR T cells between 2016-24 at Mayo Clinic, Rochester, were included in this analysis. Peripheral blood CD4, CD8 and NK counts were measured pre LD and at M1 post CAR T infusion. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff for pre LD and M1 immune cells to predict patients who were alive and in remission at 6 months (M6) post CAR T infusion. Patients who progressed or were lost to follow up prior to day 30 were excluded from M1 ROC analysis. Results: Of 140 patients, 81 were alive and in remission at M6 (Group A), while 59 had relapse or death (Group B). Axicabtagene ciloleucel was the CAR T product given in 81% of patients (114/140). Median pre LD CD4 counts were significantly lower in Group B compared to group A (143 vs 280 cells/µL, p = 0.001). No significant difference was observed in median pre LD CD8 counts (205 vs 221 cells/µL, p = 0.8). ROC analysis identified an optimal pre LD CD4 count of 124.5 cells/µL for M6 alive+remission. Lower pre LD CD4 counts (<124.5) predicted worse progression free survival (PFS) in univariate (HR = 3.02, 95% confidence interval [CI]: 1.73–5.27, p< 0.01) and multivariable analysis (MVA) adjusted for IPI and the number of prior lines (aHR = 2.54, 95% CI: 1.39–4.62, p< 0.01).Lower pre LD CD4 counts also predicted inferior overall survival (OS) in MVA (aHR = 2.27, 95% CI: 1.08–4.77, p = 0.03). (Table 1) On day 30 landmark analysis, ROC identified M1 optimal CD4 count of ≥ 99.5 cells/µL to be associated with a trend toward superior PFS (P=0.09), but not OS (p=0.90) in MVA. Median pre LD NK cell counts were significantly lower in Group B (73 vs 98 cells/µL, p = 0.04). ROC analysis identified an optimal pre LD NK count of 151 cells/µL for M6 alive + remission. Lower pre LD NK counts (<151) predicted worse PFS, both on univariate (HR = 4.17, 95% CI: 1.29–13.47, p = 0.02) and MVA (aHR = 4.64, p< 0.01). The lower pre LD NK cell count group had worse OS in MVA (aHR = 5.69, 95% CI: 1.16–28.1, p = 0.01). (Table 1) On D30 landmark analysis, M1 NK cell count of ≥ 128.5 cells/µL was associated with a trend toward superior PFS (P=0.08), but not OS (p=0.30) in MVA. Conclusions: Pre LD CD4 and NK cell counts are significantly associated with PFS and OS post CAR T therapy in patients with R/R LBCL. Pre-treatment immune subset levels may identify patients at higher risk of relapse or death after CAR-T therapy. Groups Median PFS 2 Year PFS Median OS 2 Year OS CD4 ≥124.5 cells/µL (N=75) NR 58% 3.31 years 67% CD4 <124.5 cells/µL (N=30) 2.2 months 22% 1.59 years 45% NK ≥151 cells/µL (N=17) NR 77% NR 84% NK <151 cells/µL (N=82) 10.6 months 44% 3.31 years 62%