Contributions
Abstract: PS945
Type: Poster Presentation
Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00
Location: Poster area
Background
KTE-X19 is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy under investigation for adult relapsed/refractory acute lymphoblastic leukemia. In an interim analysis of Phase 1 of ZUMA-3 (NCT02614066), we reported manageable safety and encouraging efficacy of KTE-X19; 72% of patients achieved a complete remission (CR) or CR with incomplete bone marrow recovery (CRi; Wierda et al, ASH 2018. #897).
Aims
The aim of this report is to present end of Phase 1 results of ZUMA-3.
Methods
Adults with relapsed/refractory B cell acute lymphoblastic leukemia, greater than 5% bone marrow blasts, and an Eastern Cooperative Oncology Group performance status of 0–1 received 2 × 106, 1 × 106, or 0.5 × 106 KTE-X19 cells/kg after conditioning chemotherapy. Revised adverse event (AE) management was implemented for additional patients in a 1 × 106 dose cohort: corticosteroids were given earlier at onset of Grade ≥ 2 neurologic events (NEs) and tocilizumab was used only for active toxicity. The primary endpoint was the rate of dose-limiting toxicities (DLTs). Key additional endpoints were KTE-X19 levels, incidence of AEs, minimal residual disease, and CR/CRi rate.
Results
As of 9/27/18, 45 patients had received KTE-X19, with a median follow-up of 16 months. The median age was 46 years (range, 18–77 years); 30 patients (66%) had ≥ 3 prior therapies, and the median bone marrow blasts before conditioning chemotherapy was 70% (range, 0%–97%). Six, 23, and 16 patients received 2 × 106, 1 × 106, and 0.5 × 106 KTE-X19 cells/kg, respectively. There were no DLTs in the DLT-evaluable patients. The most common Grade ≥ 3 AEs were hypotension (38%), pyrexia (38%), and thrombocytopenia (31%). There were 2 previously reported KTE-X19–related Grade 5 AEs of cerebral infarction and multiorgan failure, both in the context of cytokine release syndrome (CRS). Grade ≥ 3 CRS and NEs occurred in 13 (29%) and 17 (38%) patients, respectively. Of 41 patients with ≥ 2 months of follow-up, 68% had CR/CRi, and 73% had undetectable minimal residual disease. Of 19 patients with ≥ 2 months of follow-up treated with 1 × 106 KTE-X19 cells/kg, 16 (84%) had a CR/CRi, and the median event-free survival was 15 months. In 9 patients treated with 1 × 106 KTE-X19 cells/kg who received revised AE management, 2 (22%) had Grade 3 CRS, and 1 (11%) had Grade 3 NE, with no Grade 4/5 events.
Conclusion
KTE-X19 dosing and safety management have been successfully refined by testing 3 cell doses and evaluating a new AE management guideline with altered corticosteroids/tocilizumab use for NEs/CRS. The pivotal Phase 2 portion of ZUMA-3 is ongoing at the 1 × 106 dose with revised AE management.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Cancer immunotherapy, CD19
Abstract: PS945
Type: Poster Presentation
Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00
Location: Poster area
Background
KTE-X19 is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy under investigation for adult relapsed/refractory acute lymphoblastic leukemia. In an interim analysis of Phase 1 of ZUMA-3 (NCT02614066), we reported manageable safety and encouraging efficacy of KTE-X19; 72% of patients achieved a complete remission (CR) or CR with incomplete bone marrow recovery (CRi; Wierda et al, ASH 2018. #897).
Aims
The aim of this report is to present end of Phase 1 results of ZUMA-3.
Methods
Adults with relapsed/refractory B cell acute lymphoblastic leukemia, greater than 5% bone marrow blasts, and an Eastern Cooperative Oncology Group performance status of 0–1 received 2 × 106, 1 × 106, or 0.5 × 106 KTE-X19 cells/kg after conditioning chemotherapy. Revised adverse event (AE) management was implemented for additional patients in a 1 × 106 dose cohort: corticosteroids were given earlier at onset of Grade ≥ 2 neurologic events (NEs) and tocilizumab was used only for active toxicity. The primary endpoint was the rate of dose-limiting toxicities (DLTs). Key additional endpoints were KTE-X19 levels, incidence of AEs, minimal residual disease, and CR/CRi rate.
Results
As of 9/27/18, 45 patients had received KTE-X19, with a median follow-up of 16 months. The median age was 46 years (range, 18–77 years); 30 patients (66%) had ≥ 3 prior therapies, and the median bone marrow blasts before conditioning chemotherapy was 70% (range, 0%–97%). Six, 23, and 16 patients received 2 × 106, 1 × 106, and 0.5 × 106 KTE-X19 cells/kg, respectively. There were no DLTs in the DLT-evaluable patients. The most common Grade ≥ 3 AEs were hypotension (38%), pyrexia (38%), and thrombocytopenia (31%). There were 2 previously reported KTE-X19–related Grade 5 AEs of cerebral infarction and multiorgan failure, both in the context of cytokine release syndrome (CRS). Grade ≥ 3 CRS and NEs occurred in 13 (29%) and 17 (38%) patients, respectively. Of 41 patients with ≥ 2 months of follow-up, 68% had CR/CRi, and 73% had undetectable minimal residual disease. Of 19 patients with ≥ 2 months of follow-up treated with 1 × 106 KTE-X19 cells/kg, 16 (84%) had a CR/CRi, and the median event-free survival was 15 months. In 9 patients treated with 1 × 106 KTE-X19 cells/kg who received revised AE management, 2 (22%) had Grade 3 CRS, and 1 (11%) had Grade 3 NE, with no Grade 4/5 events.
Conclusion
KTE-X19 dosing and safety management have been successfully refined by testing 3 cell doses and evaluating a new AE management guideline with altered corticosteroids/tocilizumab use for NEs/CRS. The pivotal Phase 2 portion of ZUMA-3 is ongoing at the 1 × 106 dose with revised AE management.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Cancer immunotherapy, CD19