ABCL-043 Prognostic Factors for High-Grade B Cell Lymphoma Patients Treated With Commercial CD19-Targeted CAR T-Cell Therapy

Abstract

We hypothesized that specific clinicopathologic characteristics are correlated with survival outcomes among high-grade B cell lymphomas (HGBCL) patients treated with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. To identify the prognostic factors for survival outcomes among patients with relapsed/refractory HGBCL undergoing CAR T-cell therapy. A retrospective study was conducted for consecutive HGBCL patients who received either tisagenlecleucel (tisa-cel) or axicabtagene ciloleucel (axi-cel) CAR T-cell therapy between 2017 and 2021 at a single institution. Post-CAR T best overall response was defined as the lowest disease burden measured at any time between post-CAR T-cell therapy and additional salvage therapies. A total of 101 HGBCL patients were identified with a median follow-up of 8.3 months (range, 0.13-49.5 months) from the date of CAR T infusion. The median OS and PFS for the entire cohort were 15 months (95% CI: 8.6 months-not reached) and 4.4 months (95% CI: 3.03 months-7.23 months), respectively. The best overall response (complete response-CR and partial response) and CR rates post-CAR T were 75% (n=71) and 48% (n=46), respectively. In univariate analysis, absence of CNS involvement (OR=6.8, p=0.001), IPI score <3 at the time of apheresis (OR=3.4, p=0.003), limited-stage disease at the time of apheresis (OR=3.2, p=0.005), low LDH level at the time of apheresis (OR=5.4, p<0.001), undergoing HSCT pre-CAR T (OR=3.1, p=0.01), and not receiving salvage radiotherapy pre-CAR T (OR=4.2, p=0.03) were predictive of achieving CR post-CAR T. Sixteen patients (22%) had bulky disease (≥5 cm) as per PET/CT post-CAR T, 81% (n=13) of which were bulky pre-CAR T-bulky data was missing for 4 patients. In multivariate analysis, presence of bulky disease (≥5 cm) post-CAR T infusion was a significant prognostic factor for worse OS (HR=6.3, 95% CI: 2.9-13.6, p<0.001). Regarding PFS, high LDH at the time of apheresis, age (≥60) at the time of apheresis, and bulky disease (≥5 cm) post-CAR T infusion were significant prognostic factors for inferior PFS (HR=1.9, 95% CI: 1.02-3.8, p=0.04, HR=2.6, 95% CI: 1.2-5.6, p=0.01, HR=3.4, 95% CI: 1.6-7.5, p=0.002, respectively). Bulky disease post-CAR T is the most significant prognostic factor that can independently predict survival outcomes among HGBCL patients treated with CAR T-cell therapy.