James H. Essell, MD, is a renowned expert on blood and marrow stem cell transplants and is a medical oncologist, hematologist, and blood and marrow transplant specialist. Dr. Essell is a national expert and author who directs The US Oncology Network’s cellular treatment program. Dr. Essell is the national principle investigator for The US Oncology Network’s CAR-T clinical trials and a principal investigator for blood cancer clinical trials at OHC. He is also the Medical Director of Mercy Health Cincinnati’s Cancer and Cellular Therapy Center at The Jewish Hospital. In this video Dr. Essell discusses the 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)
Due to concerns about adverse event management, CAR T cell treatments are typically administered in a hospital setting. The infusion and monitoring of patients receiving CAR T cell treatment in nonuniversity medical centers (NMCs) and outpatient settings have not been well investigated. Liso-cel is an autologous CD19-directed 4-1BB CAR T cell product with a specified composition and equal target dosages of CD8+ and CD4+ CAR T cells. In TRANSCEND NHL 001 (NCT02631044), liso-cel therapy resulted in an ORR of 73 percent (CR rate of 53 percent) in patients with third- or later-line LBCL, with grade 3 cytokine release syndrome (CRS) in 2% and grade 3 neurological effects (NE) in 10% of patients (Abramson et al. Lancet 2020). We present liso-cel results in patients with R/R LBCL treated at NMCs in the United States in both inpatient and outpatient settings in the OUTREACH project (NCT03744676).
Methods: Patients at NMCs, both those with university links and those who had never received CAR T cell therapy, were enrolled in the study. Adults with R/R PET-positive LBCL after 2 lines of treatment and an ECOG PS of 1 were included in the study. The study included patients with grade 3–4 cytopenias, mild to moderate organ function (LVEF 40%; serum CrCl > 30 mL/min), subsequent CNS lymphoma, and prior autologous HSCT. Patients were given liso-cel at a target dose of 100 106 CAR+ T cells after leukapheresis and lymphodepleting chemotherapy (LDC). Incidence of grade 3 CRS, NEs, persistent cytopenias (Day 29 grade 3 lab results), and infections were the primary endpoints. Safety, ORR, CR rate, duration of response (DOR), and liso-cel PK were also secondary objectives. The studies on B-cell depletion were purely exploratory. NCI CTCAE v4.03 was used to grade AEs, including NEs, and Lee criteria were used to rate CRS (2014). NEs were defined as neurological AEs linked to liso-cel that were identified by the investigator. A multidisciplinary CAR T cell therapy team and standard operating procedures (SOP) for outpatient toxicity monitoring and hospitalization for CRS/NE care were present at all trial sites.
71 pts were treated with liso-cel at NMCs at the data cutoff; 52 and 19 were tracked as outpts and inpts, respectively. 65 percent of patients had de novo DLBCL, 68 percent had screening ECOG PS of 1, 82 percent were chemotherapy refractory, 31 percent had three prior regimens, and 48 percent showed signs of significant tumor burden (pre-LDC LDH 500 U/L or SPD 50 cm2). Outpts and inpts had similar demographics and baseline disease features, with differences of up to 20% in the rates of high-grade B-cell lymphoma (4 percent vs 42 percent) and DLBCL changed from indolent lymphoma (29 percent vs 0 percent ). Overall, 39 percent of patients had any grade CRS (no grade 3) and 32 percent had NEs (grade 3–4, 10%); 27 percent received tocilizumab and/or corticosteroids for CRS or NEs. Outpts and inpts had equal rates of any-grade CRS and NEs, although grade 3 NEs, infections, and extended cytopenias were statistically greater in outpts, but similar to pivotal trial findings (Table). Neutropenia (68 percent), leukopenia (45 percent), CRS (39 percent), anemia (38 percent), thrombocytopenia (37 percent), and exhaustion were the most prevalent treatment-emergent AEs (35 percent ). There were no grade 5 AEs reported. In 33 percent and 69 percent of outpts, respectively, early (study Day 4) and overall hospitalization occurred; the median time to hospitalization was 5.0 days (range 2–141) in outpts. Outpts spent 6.0 days (1–28; n = 36) in the hospital after receiving liso-cel versus 10.0 days (0–31; n = 19) among inpts; 31% of outpts were not hospitalized. All of the points could be evaluated for efficacy. The ORR was 77 percent, with a CR of 51 percent. At a median follow-up of 8.1 months and 11.3 months, respectively, the median DOR for outpts was 14.8 months (95 percent CI, 3.9 not reached [NR]) and NR (95 percent CI, 2.0 NR) for inpts (Table). Outpts and inpts have similar PK characteristics. The target decrease of CD19+ B lymphocytes in peripheral blood was likewise identical in oupts and inpts, and it lasted for a year.
Conclusions: Patients with R/R LBCL were successfully treated with liso-cel in both outpatient and inpatient settings at NMCs, and toxicities associated with CAR T cell therapy were evaluated using SOPs and multidisciplinary teams. In both outpts and inpts, Liso-cel demonstrated long-term clinical effectiveness with a satisfactory safety profile. Severe CRS and NEs were uncommon, as was the use of tocilizumab and/or corticosteroids. These findings support the use of liso-cel in NMCs and outpatient settings.