Contributions
Abstract: EP541
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Concerns about adverse event management related to CAR T cell therapy have resulted in administration of this therapy largely in an inpatient setting. Infusion and monitoring of patients (pts) who receive CAR T cell therapy at nonuniversity medical centers (NMCs) and in outpatient settings have not been studied specifically.
Aims
To evaluate safety and efficacy of liso-cel in pts with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) across inpatient and outpatient settings at NMCs in OUTREACH (NCT03744676).
Methods
This open-label, multicenter, phase 2 study enrolled adult pts with R/R LBCL at NMCs, including centers naïve to CAR T cell therapy. Eligible pts had R/R PET-positive disease after ≥2 lines of prior systemic therapy, ECOG PS ≤1, and adequate organ function. Prior autologous HSCT was permitted. After leukapheresis and lymphodepleting chemotherapy, pts received sequential infusions of equal target doses of CD8+ and CD4+ cells at a total target dose of 100 × 106 CAR+ T cells. The primary endpoint was incidence of grade ≥3 cytokine release syndrome (CRS) graded per 2014 Lee criteria, neurological events (NEs), prolonged cytopenias (Day 29 grade ≥3 lab values), and infections. Secondary endpoints were safety and overall response rate (ORR). All study sites had a multidisciplinary CAR T cell therapy team and standard operating procedures (SOPs) for toxicity monitoring/management of pts treated and/or monitored as outpatients.
Results
At data cutoff, 46 pts (inpatients, n = 16, outpatients, n = 30) were treated with liso-cel. Median age was 63 (range, 34−83) y, 63% had diffuse LBCL not otherwise specified, and 91% were refractory to last therapy. Inpatients and outpatients had similar demographics and baseline disease characteristics. CRS was reported in 6 (38%) inpatients and 13 (43%) outpatients, with no grade ≥3 events. NEs were reported in 5 (31%) inpatients and 9 (30%) outpatients, with 1 grade 3 event in the inpatient group and 2 grade 3 events in the outpatient group. Median (range) time to onset of CRS and NEs, respectively, was 2.5 (1‒3) and 10 (3‒16) days for inpatients and 5 (2‒9) and 9 (6‒14) days for outpatients. Tocilizumab and/or corticosteroid use for CRS and/or NE management was generally low (inpatients, n = 3 [19%]; outpatients, n = 6 [20%]). Overall, the most common treatment-emergent adverse events (TEAEs) were neutropenia (32, 70%), leukopenia (22, 48%), and anemia (18, 39%). Any grade infections occurred in 3 (19%) inpatients and 8 (27%) outpatients, with 1 grade 3 bacterial infection in inpatients and 5 grade 3−4 pathogen unspecified infections in outpatients. Prolonged cytopenias (grade ≥3 lab values at Day 29) were reported for 2 (13%) inpatients and 9 (30%) outpatients. No grade 5 TEAEs were reported. Early (study Day ≤4) and overall hospitalization in outpatients was reported in 27% and 63%, respectively; median time to hospitalization was 5 (2–61) days and median length of stay was 6 (1–28) days. For efficacy-evaluable pts (n = 44), ORR was 75% for inpatients and 79% for outpatients; CR rates were 50% and 61%, respectively.
Conclusion
Liso-cel was successfully administered to pts with R/R LBCL in the outpatient setting and pts were monitored for CAR T cell therapy–related toxicities by multidisciplinary teams using SOPs. Incidences of severe CRS and NEs and tocilizumab and/or corticosteroid use were similar in inpatients and outpatients. Data were consistent with pivotal study observations (Abramson, The Lancet 2020). Updated data with longer follow-up will be presented.
Keyword(s): CAR-T, Safety
Abstract: EP541
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Concerns about adverse event management related to CAR T cell therapy have resulted in administration of this therapy largely in an inpatient setting. Infusion and monitoring of patients (pts) who receive CAR T cell therapy at nonuniversity medical centers (NMCs) and in outpatient settings have not been studied specifically.
Aims
To evaluate safety and efficacy of liso-cel in pts with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) across inpatient and outpatient settings at NMCs in OUTREACH (NCT03744676).
Methods
This open-label, multicenter, phase 2 study enrolled adult pts with R/R LBCL at NMCs, including centers naïve to CAR T cell therapy. Eligible pts had R/R PET-positive disease after ≥2 lines of prior systemic therapy, ECOG PS ≤1, and adequate organ function. Prior autologous HSCT was permitted. After leukapheresis and lymphodepleting chemotherapy, pts received sequential infusions of equal target doses of CD8+ and CD4+ cells at a total target dose of 100 × 106 CAR+ T cells. The primary endpoint was incidence of grade ≥3 cytokine release syndrome (CRS) graded per 2014 Lee criteria, neurological events (NEs), prolonged cytopenias (Day 29 grade ≥3 lab values), and infections. Secondary endpoints were safety and overall response rate (ORR). All study sites had a multidisciplinary CAR T cell therapy team and standard operating procedures (SOPs) for toxicity monitoring/management of pts treated and/or monitored as outpatients.
Results
At data cutoff, 46 pts (inpatients, n = 16, outpatients, n = 30) were treated with liso-cel. Median age was 63 (range, 34−83) y, 63% had diffuse LBCL not otherwise specified, and 91% were refractory to last therapy. Inpatients and outpatients had similar demographics and baseline disease characteristics. CRS was reported in 6 (38%) inpatients and 13 (43%) outpatients, with no grade ≥3 events. NEs were reported in 5 (31%) inpatients and 9 (30%) outpatients, with 1 grade 3 event in the inpatient group and 2 grade 3 events in the outpatient group. Median (range) time to onset of CRS and NEs, respectively, was 2.5 (1‒3) and 10 (3‒16) days for inpatients and 5 (2‒9) and 9 (6‒14) days for outpatients. Tocilizumab and/or corticosteroid use for CRS and/or NE management was generally low (inpatients, n = 3 [19%]; outpatients, n = 6 [20%]). Overall, the most common treatment-emergent adverse events (TEAEs) were neutropenia (32, 70%), leukopenia (22, 48%), and anemia (18, 39%). Any grade infections occurred in 3 (19%) inpatients and 8 (27%) outpatients, with 1 grade 3 bacterial infection in inpatients and 5 grade 3−4 pathogen unspecified infections in outpatients. Prolonged cytopenias (grade ≥3 lab values at Day 29) were reported for 2 (13%) inpatients and 9 (30%) outpatients. No grade 5 TEAEs were reported. Early (study Day ≤4) and overall hospitalization in outpatients was reported in 27% and 63%, respectively; median time to hospitalization was 5 (2–61) days and median length of stay was 6 (1–28) days. For efficacy-evaluable pts (n = 44), ORR was 75% for inpatients and 79% for outpatients; CR rates were 50% and 61%, respectively.
Conclusion
Liso-cel was successfully administered to pts with R/R LBCL in the outpatient setting and pts were monitored for CAR T cell therapy–related toxicities by multidisciplinary teams using SOPs. Incidences of severe CRS and NEs and tocilizumab and/or corticosteroid use were similar in inpatients and outpatients. Data were consistent with pivotal study observations (Abramson, The Lancet 2020). Updated data with longer follow-up will be presented.
Keyword(s): CAR-T, Safety