Contributions
Abstract: PS1067
Type: Poster Presentation
Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00
Location: Poster area
Background
Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved in the European Union and United States for patients with relapsed/refractory large B cell lymphoma with ≥ 2 prior systemic therapies. In the 2-year follow-up of ZUMA-1, the objective response rate was 83% with a complete response rate of 58%. Grade ≥ 3 cytokine release syndrome (CRS) and neurologic events (NE) occurred in 11% and 32% of patients, respectively; 26% of patients received steroids, and 43% received tocilizumab (Locke et al. Lancet Oncol. 2019). A safety expansion cohort was added to evaluate the effect of earlier steroid use on the rates of these adverse events (AEs).
Aims
To assess the impact of early steroid use on outcomes in patients treated with axi-cel.
Methods
Eligible patients with relapsed/refractory large B cell lymphoma were leukapheresed and received conditioning chemotherapy followed by a target dose of 2 × 106 anti-CD19 CAR T cells/kg. Patients in this cohort received early steroid intervention starting at Grade 1 NE and at Grade 1 CRS when no improvement was observed after 3 days of supportive care. The primary endpoint for this cohort was incidence and severity of CRS and NE.
Results
As of September 14, 2018, 21 of 40 planned patients received axi-cel with a minimum follow-up of 1 month (median, 2.6 months). The median age was 63 years (range, 36 – 73), 67% were male, 81% had disease stage III-IV, 76% were relapsed/refractory to ≥ second-line therapy, and 10% had relapsed post-autologous stem cell transplantation. Seventy-six percent of patients received steroids and 81% received tocilizumab. Most patients (81%) had Grade ≥ 3 AEs, most commonly neutrophil count decreased (33%), anemia (29%), and pyrexia (24%). Grade ≥ 3 NE occurred in 10% of patients; the most common symptoms were somnolence (10%) and confusional state (10%). Grade 1 and 2 NE occurred in 38% and 5% of patients, respectively. No patient had Grade ≥ 3 CRS; 33% of patients had Grade 1 CRS and 67% had Grade 2. There were no deaths due to AEs; 1 patient died due to disease progression. The objective response rate per investigator assessment was 76% with 48% of patients achieving a complete response. Pharmacokinetic data will be presented.
Conclusion
Early use of steroids may help in managing severe CRS and NE by potentially reducing their incidence in patients treated with CAR T cell therapy without affecting response rates. Optimizing AE management may help to further improve the benefit:risk profile of CAR T cell therapy.
Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): Cancer immunotherapy, CD19, Non-Hodgkin's lymphoma
Abstract: PS1067
Type: Poster Presentation
Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00
Location: Poster area
Background
Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved in the European Union and United States for patients with relapsed/refractory large B cell lymphoma with ≥ 2 prior systemic therapies. In the 2-year follow-up of ZUMA-1, the objective response rate was 83% with a complete response rate of 58%. Grade ≥ 3 cytokine release syndrome (CRS) and neurologic events (NE) occurred in 11% and 32% of patients, respectively; 26% of patients received steroids, and 43% received tocilizumab (Locke et al. Lancet Oncol. 2019). A safety expansion cohort was added to evaluate the effect of earlier steroid use on the rates of these adverse events (AEs).
Aims
To assess the impact of early steroid use on outcomes in patients treated with axi-cel.
Methods
Eligible patients with relapsed/refractory large B cell lymphoma were leukapheresed and received conditioning chemotherapy followed by a target dose of 2 × 106 anti-CD19 CAR T cells/kg. Patients in this cohort received early steroid intervention starting at Grade 1 NE and at Grade 1 CRS when no improvement was observed after 3 days of supportive care. The primary endpoint for this cohort was incidence and severity of CRS and NE.
Results
As of September 14, 2018, 21 of 40 planned patients received axi-cel with a minimum follow-up of 1 month (median, 2.6 months). The median age was 63 years (range, 36 – 73), 67% were male, 81% had disease stage III-IV, 76% were relapsed/refractory to ≥ second-line therapy, and 10% had relapsed post-autologous stem cell transplantation. Seventy-six percent of patients received steroids and 81% received tocilizumab. Most patients (81%) had Grade ≥ 3 AEs, most commonly neutrophil count decreased (33%), anemia (29%), and pyrexia (24%). Grade ≥ 3 NE occurred in 10% of patients; the most common symptoms were somnolence (10%) and confusional state (10%). Grade 1 and 2 NE occurred in 38% and 5% of patients, respectively. No patient had Grade ≥ 3 CRS; 33% of patients had Grade 1 CRS and 67% had Grade 2. There were no deaths due to AEs; 1 patient died due to disease progression. The objective response rate per investigator assessment was 76% with 48% of patients achieving a complete response. Pharmacokinetic data will be presented.
Conclusion
Early use of steroids may help in managing severe CRS and NE by potentially reducing their incidence in patients treated with CAR T cell therapy without affecting response rates. Optimizing AE management may help to further improve the benefit:risk profile of CAR T cell therapy.
Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): Cancer immunotherapy, CD19, Non-Hodgkin's lymphoma
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