Contributions
Abstract: S799
Type: Oral Presentation
Presentation during EHA23: On Saturday, June 16, 2018 from 11:30 - 11:45
Location: Room A1
Background
Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy with a high rate of durable complete responses and a manageable safety profile in adult patients (pts) with R/R DLBCL.
Aims
To report long-term follow up of safety and efficacy in a single-arm, open-label, global phase 2 trial of tisagenlecleucel in pts ≥18 y with R/R DLBCL (JULIET; NCT02445248).
Methods
Eligible pts had r/r DLBCL, received ≥2 lines of therapy, including rituximab and anthracycline, and were ineligible for/failed autologous stem cell transplant (ASCT). Centrally manufactured CAR T cells were provided using cryopreserved apheresis and a global supply chain. The primary endpoint was best ORR (CR + PR) per independent review committee. Efficacy results are reported for pts in the main cohort with ≥3 mo follow-up or earlier discontinuation; safety is reported for all infused pts.
Results
At data cutoff (8 Dec 2017), 165 pts were enrolled and 111 infused (95 with US-manufactured [main cohort] and 16 with EU-manufactured [cohort A] tisagenlecleucel) with a single dose of tisagenlecleucel (median, 3.0×108 [range, 0.1-6.0×108] cells). 92% of pts received bridging therapy and 93% received lymphodepleting chemotherapy. Median time from infusion to data cutoff, 13.9 mo. Median age, 56 y (range, 22-76; 23% >65 y). At study entry, 76% of infused pts had stage III/IV disease, 17% had double/triple hits in MYC/BCL2/BCL6. 57% had germinal center B-cell; 41% had activated B-cell molecular subtypes. Median number of prior lines of antineoplastic therapy, 3 (range, 1-6; 95% had ≥2); 49% had prior ASCT. 93 pts had ≥3 mo and 81 pts had ≥12 mo of follow-up or discontinued earlier and were evaluable for efficacy. Best ORR was 52% (95% CI, 41-62) with 40% CR and 12% PR. Response rates were consistent across prognostic subgroups (including prior ASCT and double-hit lymphoma). Median duration of response was not reached; the 12-mo probability of being relapse-free was 65% (95% CI, 49-78; max follow-up, 17.3 mo). Median OS among all infused pts was 11.7 mo (95% CI, 6.6-NE); OS probability at mo 12, 49% (95% CI, 38.5-59). No pts proceeded to allo/ASCT while in remission. Tisagenlecleucel was detected in peripheral blood by qPCR for ≤693 days in responders. Grade (G)3 or 4 AEs of special interest ≤8 weeks of infusion included cytokine release syndrome (CRS; 14% G3 and 8% G4 by the Penn grading scale and managed by a protocol-specific algorithm), neurologic AEs (12%, managed with supportive care; no cases of cerebral edema were observed), cytopenias lasting >28 days (32%), infections (20%), and febrile neutropenia (14%). 15% received tocilizumab for CRS management. 3 pts died ≤30 days of infusion (all disease progression). No deaths were attributed to tisagenlecleucel or CRS. Since previous reports, no new deaths occurred due to causes other than disease progression. Analyses to better characterize and predict severe CRS, including relationships with baseline clinical/laboratory parameters, cytokines, dose, cellular kinetics and neurologic events will be presented.
Conclusion
Tisagenlecleucel produces high response rates in a cohort of highly pretreated adult pts with r/r DLBCL. With longer follow-up, these results confirm findings of an earlier primary analysis and show prolonged durable responses can be achieved. Centralized manufacturing was feasible in the first global study of CAR T cell therapy in DLBCL. CRS and other AEs could be effectively and reproducibly managed by appropriately trained investigators without treatment-related mortality.
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): Diffuse large B cell lymphoma, Targeted therapy
Abstract: S799
Type: Oral Presentation
Presentation during EHA23: On Saturday, June 16, 2018 from 11:30 - 11:45
Location: Room A1
Background
Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy with a high rate of durable complete responses and a manageable safety profile in adult patients (pts) with R/R DLBCL.
Aims
To report long-term follow up of safety and efficacy in a single-arm, open-label, global phase 2 trial of tisagenlecleucel in pts ≥18 y with R/R DLBCL (JULIET; NCT02445248).
Methods
Eligible pts had r/r DLBCL, received ≥2 lines of therapy, including rituximab and anthracycline, and were ineligible for/failed autologous stem cell transplant (ASCT). Centrally manufactured CAR T cells were provided using cryopreserved apheresis and a global supply chain. The primary endpoint was best ORR (CR + PR) per independent review committee. Efficacy results are reported for pts in the main cohort with ≥3 mo follow-up or earlier discontinuation; safety is reported for all infused pts.
Results
At data cutoff (8 Dec 2017), 165 pts were enrolled and 111 infused (95 with US-manufactured [main cohort] and 16 with EU-manufactured [cohort A] tisagenlecleucel) with a single dose of tisagenlecleucel (median, 3.0×108 [range, 0.1-6.0×108] cells). 92% of pts received bridging therapy and 93% received lymphodepleting chemotherapy. Median time from infusion to data cutoff, 13.9 mo. Median age, 56 y (range, 22-76; 23% >65 y). At study entry, 76% of infused pts had stage III/IV disease, 17% had double/triple hits in MYC/BCL2/BCL6. 57% had germinal center B-cell; 41% had activated B-cell molecular subtypes. Median number of prior lines of antineoplastic therapy, 3 (range, 1-6; 95% had ≥2); 49% had prior ASCT. 93 pts had ≥3 mo and 81 pts had ≥12 mo of follow-up or discontinued earlier and were evaluable for efficacy. Best ORR was 52% (95% CI, 41-62) with 40% CR and 12% PR. Response rates were consistent across prognostic subgroups (including prior ASCT and double-hit lymphoma). Median duration of response was not reached; the 12-mo probability of being relapse-free was 65% (95% CI, 49-78; max follow-up, 17.3 mo). Median OS among all infused pts was 11.7 mo (95% CI, 6.6-NE); OS probability at mo 12, 49% (95% CI, 38.5-59). No pts proceeded to allo/ASCT while in remission. Tisagenlecleucel was detected in peripheral blood by qPCR for ≤693 days in responders. Grade (G)3 or 4 AEs of special interest ≤8 weeks of infusion included cytokine release syndrome (CRS; 14% G3 and 8% G4 by the Penn grading scale and managed by a protocol-specific algorithm), neurologic AEs (12%, managed with supportive care; no cases of cerebral edema were observed), cytopenias lasting >28 days (32%), infections (20%), and febrile neutropenia (14%). 15% received tocilizumab for CRS management. 3 pts died ≤30 days of infusion (all disease progression). No deaths were attributed to tisagenlecleucel or CRS. Since previous reports, no new deaths occurred due to causes other than disease progression. Analyses to better characterize and predict severe CRS, including relationships with baseline clinical/laboratory parameters, cytokines, dose, cellular kinetics and neurologic events will be presented.
Conclusion
Tisagenlecleucel produces high response rates in a cohort of highly pretreated adult pts with r/r DLBCL. With longer follow-up, these results confirm findings of an earlier primary analysis and show prolonged durable responses can be achieved. Centralized manufacturing was feasible in the first global study of CAR T cell therapy in DLBCL. CRS and other AEs could be effectively and reproducibly managed by appropriately trained investigators without treatment-related mortality.
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): Diffuse large B cell lymphoma, Targeted therapy