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Chimeric antigen receptor T-cells (CAR-T) are widely used for the treatment of relapsed/refractory Diffuse large B cell lymphoma (DLBCL). The data for CAR-T cell therapy in patients with extra-nodal(EN) lymphoma is restricted. We included 126 consecutive patients with DLBCL treated with commercially available CAR-T cells (tisagenlecleucel, n=100, 79.4% and axicabtagene ciloleucel, n=26, 20.6%). At lymphodepletion , 72/126(57%) had EN disease, 42/126(33%) patients had nodal disease (ND)-only and 12/126(10%) showed no disease assessed by PET-CT. There were no signi cant differences in CAR-T related toxicities and in the median PFS between EN patients and ND [10.76(95% CI: 7.8-13.6) vs 14.1 (95% CI:10-18.1) months, p =0.126)]. Similarly, median OS was not signi cantly different [15.36 (95% CI 12.5-18.2) vs. 18.4 (95% CI 14.8-22.1) months , p =0.100]. Subgroup analysis according to the number of EN involved sites showed that median PFS and OS were signi cantly higher in patients with ≤ 2 EN sites [12.3 months (95% CI 9-15.5)] vs 4.28 months (95% CI 0.6-7.9), p=0.010] compared to patients with EN sites,) vs 8.7 months (95% CI 4.6-12.8), p=0.05]. In multivariate cox regression analysis, increased number sites of EN disease and high LDH at lymphodepletion negatively impacted PFS (p=0.021 and <0.001, respectively), while sex, type of product administered, age and performance status did not predict PFS and OS. Of note, all the patients with involvement of gastrointestinal tract (n= 9), urinary tract (n= 9), or pharynx (n= 3) at lymphodepletion progressed or had an early relapse.In conclusions, both short and long term outcomes were similar in patients with EN and patients with ND at lymphodepletion, however patients with speci c sites of EN disease may demonstrate grim prognosis.

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