Identification of an optimal absolute lymphocyte count at leukapheresis in patients with lymphoma treated with CART.

Abstract

T-cell fitness can be impaired in patients with large B-cell lymphoma (LBCL) planned for CART (chimeric antigen receptor T-cell therapy). Although absolute lymphocyte count (ALC) at the time of leukapheresis has been shown to associate with outcomes in patients with LBCL treated axicabtagene ciloleucel (axi-cel), no threshold has been identified. This is a multicenter retrospective study including 1 axi-cel training and validation cohort, and 1 mixed-product validation cohort. The change-point method was used to identify an ALC threshold associating with optimal progression-free survival (PFS). Three hundred seventy-nine patients were included in the axi-cel training cohort. ALC as a continuous variable was associated with complete response on day 30 (median, 0.79 × 10³/μL vs 0.63 × 10³/μL; P = .004). An ALC of 0.34 × 10³/μL was identified as the optimal threshold for PFS (7 vs 3 months; P = .0013). The association was confirmed in the axi-cel validation cohort (165 patients; 19.8 vs 3.5 months; P = .04) but not in the mixed validation cohort (163 patients; 5 vs 1.5 months; P = .3). On univariate analysis, characteristics associated with ALC above the threshold included low International Prognostic Index score (P = .02), low serum C-reactive protein level (P = .02), low serum ferritin level (P < .001), and low number of prior lines of systemic therapy (P = .02). An ALC of >0.34 × 10³/μL at the time of apheresis is associated with optimal outcomes in patients with LBCL treated with axi-cel. A deeper investigation of the impact of prior therapies on the number and phenotype of lymphocytes at time of apheresis is warranted.