EHA Library - The official digital education library of European Hematology Association (EHA)

Abstract

Abstract: LB2604

Type: Late Breaking Oral Session

Presentation during EHA22: On Sunday, June 25, 2017 from 11:15 - 13:30

Location: Hall A

Background
CTL019 is an investigational chimeric antigen receptor (CAR) T-cell therapy with a high rate of durable complete responses (CRs) and a manageable safety profile in a previously reported single-center trial in adult patients (pts) with R/R DLBCL.

Aims
Results of a planned interim analysis of a single-arm, open-label, multicenter, global phase 2 trial of CTL019 in pts ≥ 18 y with R/R DLBCL (JULIET; NCT02445248) are reported.

Methods
Industry-manufactured CAR T cells were provided to pts at 27 centers on 4 continents using a global supply chain. Pts had received ≥ 2 lines of chemotherapy and had disease progression after or were ineligible for autologous stem cell transplant (autoSCT). Autologous T cells were transduced with a lentiviral vector encoding an anti-CD19 CAR, expanded, cryopreserved, shipped, and infused at study sites. The primary endpoint (centrally reviewed by an independent review committee) was best overall response rate (ORR: CR partial response [PR]).

Results
141 pts were enrolled. Following restaging, bridging therapy, and lymphodepleting chemotherapy (fludarabine 25 mg/m2/cyclophosphamide 250 mg/m2/day × 3 days or bendamustine 90 mg/m2/day × 2 days), 85 pts received a single dose of CTL019 transduced cells (median, 3.1 × 108 [range, 0.1-6.0 × 108] cells). Median time from infusion to data cutoff (20 December 2016) was 3.7 mo. Median age was 56 y (range, 24-75) and median prior lines of antineoplastic therapy, 3 (range, 2-7). 51% of pts had prior autoSCT. Among 51 pts with ≥ 3 mo follow-up or earlier discontinuation, best ORR was 59% (95% CI, 44% to 72%) with 43% CR and 16% PR; the primary endpoint was met. CR and PR rates at 3 mo were 37% and 8%, respectively. All pts in CR at 3 mo remained in CR at data cutoff. Efficacy was observed across prognostic subgroups. Median duration of response was not reached. CTL019 was detectable in peripheral blood by quantitative PCR for up to 355 days in responders. Cytokine release syndrome (CRS) was graded using the Penn scale and managed by a protocol-specific algorithm. CRS occurred in 57% of infused pts (17% grade 3; 9% grade 4); no CRS-associated deaths occurred. 16% of pts received tocilizumab for CRS management. 13% of pts had grade 3/4 neurologic adverse events (AEs), managed with supportive care; no cerebral edema was reported. Grade 3/4 cytopenias lasting > 28 days and grade 3/4 febrile neutropenia occurred in 21% and 14% of pts, respectively. 3 pts died from disease progression within 30 days of infusion. No deaths were attributed to CTL019.

Conclusion
This planned interim analysis of a global study of CTL019 in adults with R/R DLBCL confirms the high response rates and durable CRs observed in the previous single-center experience in a cohort of highly pretreated patients. Centralized manufacturing was feasible. CTL019 was generally tolerated without instance of treatment-related mortality. CRS and other AEs could be effectively and reproducibly managed by appropriately trained investigators.

Session topic: 20. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): CD19, Diffuse large B cell lymphoma, T cell

Abstract: LB2604

Type: Late Breaking Oral Session

Presentation during EHA22: On Sunday, June 25, 2017 from 11:15 - 13:30

Location: Hall A

Background
CTL019 is an investigational chimeric antigen receptor (CAR) T-cell therapy with a high rate of durable complete responses (CRs) and a manageable safety profile in a previously reported single-center trial in adult patients (pts) with R/R DLBCL.

Aims
Results of a planned interim analysis of a single-arm, open-label, multicenter, global phase 2 trial of CTL019 in pts ≥ 18 y with R/R DLBCL (JULIET; NCT02445248) are reported.

Methods
Industry-manufactured CAR T cells were provided to pts at 27 centers on 4 continents using a global supply chain. Pts had received ≥ 2 lines of chemotherapy and had disease progression after or were ineligible for autologous stem cell transplant (autoSCT). Autologous T cells were transduced with a lentiviral vector encoding an anti-CD19 CAR, expanded, cryopreserved, shipped, and infused at study sites. The primary endpoint (centrally reviewed by an independent review committee) was best overall response rate (ORR: CR partial response [PR]).

Results
141 pts were enrolled. Following restaging, bridging therapy, and lymphodepleting chemotherapy (fludarabine 25 mg/m2/cyclophosphamide 250 mg/m2/day × 3 days or bendamustine 90 mg/m2/day × 2 days), 85 pts received a single dose of CTL019 transduced cells (median, 3.1 × 108 [range, 0.1-6.0 × 108] cells). Median time from infusion to data cutoff (20 December 2016) was 3.7 mo. Median age was 56 y (range, 24-75) and median prior lines of antineoplastic therapy, 3 (range, 2-7). 51% of pts had prior autoSCT. Among 51 pts with ≥ 3 mo follow-up or earlier discontinuation, best ORR was 59% (95% CI, 44% to 72%) with 43% CR and 16% PR; the primary endpoint was met. CR and PR rates at 3 mo were 37% and 8%, respectively. All pts in CR at 3 mo remained in CR at data cutoff. Efficacy was observed across prognostic subgroups. Median duration of response was not reached. CTL019 was detectable in peripheral blood by quantitative PCR for up to 355 days in responders. Cytokine release syndrome (CRS) was graded using the Penn scale and managed by a protocol-specific algorithm. CRS occurred in 57% of infused pts (17% grade 3; 9% grade 4); no CRS-associated deaths occurred. 16% of pts received tocilizumab for CRS management. 13% of pts had grade 3/4 neurologic adverse events (AEs), managed with supportive care; no cerebral edema was reported. Grade 3/4 cytopenias lasting > 28 days and grade 3/4 febrile neutropenia occurred in 21% and 14% of pts, respectively. 3 pts died from disease progression within 30 days of infusion. No deaths were attributed to CTL019.

Conclusion
This planned interim analysis of a global study of CTL019 in adults with R/R DLBCL confirms the high response rates and durable CRs observed in the previous single-center experience in a cohort of highly pretreated patients. Centralized manufacturing was feasible. CTL019 was generally tolerated without instance of treatment-related mortality. CRS and other AEs could be effectively and reproducibly managed by appropriately trained investigators.

Session topic: 20. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): CD19, Diffuse large B cell lymphoma, T cell

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