Background: Relapsed/refractory (R/R) DLBCL is associated with high healthcare resource utilization (HRU) and cost (Danese 2017). Patients with R/R DLBCL have poor outcome with median OS <10 months (Van den Neste 2015). As transformative therapies are being developed for these patients, resource utilization may become an issue. Liso-cel is an investigational defined composition, CD19-directed 4-1BB CAR T cell product administered at a precise dose of CD8 and CD4 CAR T cells in a multicenter, seamless design Phase 1 pivotal trial of (R/R) DLBCL (TRANSCEND NHL 001; NCT02631044). In a recent analysis with 6 months follow-up, liso-cel treatment demonstrated a best overall response rate of 75% (55% CR) with low rates of severe cytokine release syndrome (1%) and neurologic events (13%) (Abramson 2018). The objective of this analysis is to characterize HRU, including site of care, associated with liso-cel in an interim analysis of the TRANSCEND pivotal trial.
Methods: Eligible patients with R/R DLBCL, PMBCL, FL grade 3B, or MCL (≥18 years who received ≥2 lines of therapy) and adequate organ function (no minimum ALC requirement for apheresis) received lymphodepletion (LD) with fludarabine and cyclophosphamide, followed by a single flat-dose infusion of liso-cel at one of two dose levels (DL1, 5 × 107 cells; DL2, 1 × 108 cells). Clinical site of care for liso-cel infusion was not protocol-defined. HRU was collected at all sites.
Results: 94 patients (91 patients in the efficacy database and 3 patients from the safety database that were not in the electronic clinical as of data cut) were included in the preliminary site of care analysis. 86 patients received liso-cel in the inpatient setting and 8 patients in the outpatient setting. Mean (SD) number of hospital days was 15.6 (9.6) and 9.3 (11.9) among patients receiving inpatient and outpatient liso-cel infusion, respectively, reflecting a 40% lower duration in mean hospital days. The median time to hospitalization following outpatient infusion was 5 days (range: 4-22). No patients infused in the outpatient setting required subsequent ICU care or received corticosteroids, and only one received tocilizumab for cytokine release syndrome (CRS). Of all treated patients in the efficacy database (n=91), 12% (11/91) of patients required ICU care for management of toxicity, including 10% (9/91) for CRS or neurotoxicity and 3% (3/91) for management of acute respiratory events. Rates of hemofiltration and ventilation for patients in this cohort were 2% (2/91) and 7% (6/91), respectively. Outcomes based on site of administration will be presented (based on longer follow-up).
Conclusions: CAR T cell therapy represents an additional treatment option for patients with R/R DLBCL. Liso-cel has been infused in both the inpatient and outpatient setting. Outpatient infusion was associated with 40% lower mean hospital days compared with infusions administered in the inpatient setting. As enrollment is ongoing, updated data will be reported.
Palomba:Celgene: Consultancy; Pharmacyclics: Consultancy. Garcia:Juno Therapeutics, a fully owned subsidiary of Celgene: Employment, Equity Ownership. Wang:Juno Therapeutics, a fully owned subsidiary of Celgene: Employment, Equity Ownership. Dehner:Juno Therapeutics, a fully owned subsidiary of Celgene: Employment, Equity Ownership. Chung:Juno Therapeutics, a fully owned subsidiary of Celgene: Employment. Maloney:Janssen Scientific Affairs: Honoraria; GlaxoSmithKline: Research Funding; Seattle Genetics: Honoraria; Juno Therapeutics: Research Funding; Roche/Genentech: Honoraria.
Asterisk with author names denotes non-ASH members.