Outreach: Results from a Phase 2 Study of Lisocabtagene Maraleucel (liso-cel) Administered As Inpatient (Inpt) or Outpatient (Outpt) Treatment in the Nonuniversity Setting in Patients (Pts) with R/R Large B-Cell Lymphoma (LBCL)

Background: CAR T cell therapies are generally administered in an inpt setting owing to concerns of AE management. Infusion and monitoring of pts who receive CAR T cell therapy at nonuniversity medical centers (NMC) and in outpt settings have not been studied specifically. Liso-cel is an autologous CD19-directed, defined composition, 4-1BB CAR T cell product administered at equal target doses of CD8 + and CD4 + CAR + T cells. In TRANSCEND NHL 001 (NCT02631044) in pts with third- or later-line LBCL, liso-cel treatment showed an ORR of 73% (CR rate, 53%), with grade ≥ 3 cytokine release syndrome (CRS) in 2%, and grade ≥ 3 neurological events (NE) in 10% of pts (Abramson et al. Lancet 2020). We report outcomes of liso-cel in pts with R/R LBCL across inpt and outpt settings at NMCs in the United States treated in the OUTREACH study (NCT03744676). Methods: The study enrolled pts at NMCs, including those with university affiliations and centers naïve to CAR T cell therapy. Adults with R/R PET-positive LBCL after ≥ 2 lines of therapy and ECOG PS ≤ 1 were eligible. Pts with grade 3-4 cytopenias, mild to moderate organ function (LVEF ≥ 40%; serum CrCl > 30 mL/min), secondary CNS lymphoma, and prior autologous HSCT were eligible. After leukapheresis and lymphodepleting chemotherapy (LDC), pts received liso-cel at a target dose of 100 × 10 6 CAR + T cells. Primary endpoint was incidence of grade ≥ 3 CRS, NEs, prolonged cytopenias (Day 29 grade ≥ 3 lab values), and infections. Secondary endpoints included safety, ORR, CR rate, duration of response (DOR), and liso-cel PK. B-cell depletion analyses were exploratory. AEs, including NEs, were graded using NCI CTCAE v4.03; CRS was graded per Lee criteria (2014). NEs were defined as investigator-identified neurological AEs related to liso-cel. All study sites had a multidisciplinary CAR T cell therapy team and standard operating procedures (SOP) for outpt monitoring of toxicity and admission for CRS/NE management. Results: At data cutoff, 71 pts were treated with liso-cel at NMCs; 52 and 19 were monitored as outpts and inpts, respectively. Median age was 65 years (range, 28-83; ≥ 65 years, 51%; ≥ 75 years, 18%); 65% of pts had de novo DLBCL, 68% had screening ECOG PS of 1, 82% were chemotherapy refractory, 31% had ≥ 3 prior therapies, and 48% had markers of high tumor burden (pre-LDC LDH ≥ 500 U/L or SPD ≥ 50 cm 2). Demographics and baseline disease characteristics were generally similar in outpts and inpts, respectively, w