Contributions
Abstract: S800
Type: Oral Presentation
Presentation during EHA23: On Saturday, June 16, 2018 from 11:45 - 12:00
Location: Room A1
Background
Lisocabtagene maraleucel (liso-cel; JCAR017) is a CD19-directed 4-1BB CAR T cell product administered in defined composition at a precise dose of CD8 and CD4 CAR T cells. A multicenter, seamless design pivotal phase 1 trial of liso-cel in R/R B-NHL (NCT02631044) has enrolled.
Aims
Long-term follow up of the initial cohort is presented herein.
Methods
Pts with R/R DLBCL, PMBCL, FL3B, or MCL and adequate organ function are eligible. Treatment includes lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel. Multiple dose levels (DLs) and administration schedules were evaluated; DL2 (108 CAR T cells) was chosen for the pivotal cohort. The FULL dataset includes all pts in the initial DLBCL cohort (DLBCL NOS, PMBCL, FL3B) treated with liso-cel at all DLs; CORE dataset includes only pts meeting inclusion criteria for the pivotal cohort, including DLBCL NOS (de novo or transformed from FL) and high grade lymphoma. Study objectives include safety, PK, and antitumor response.
Results
As of Oct 9, 2017, 91 pts were treated and evaluable for safety, 88 for efficacy. Pt characteristics were previously reported (Abramson ASH 2017). CRS was seen in 35% of pts; a single pt (1%) developed grade 3-4 CRS. Neurotoxicity (NT) developed in 19% of pts including 12% grade 3-4; all but one event resolved at time of data snapshot. Median onset of CRS and NT was 5 and 10 days respectively. Nineteen pts (21%) received tocilizumab and/or dexamethasone. Long term safety, including B cell aplasia, infections, and cytopenias, will be reported.
Best ORR in FULL and CORE was 74% (65/88) and 80% (52/65), respectively; best CR was 52% (46/88) in FULL and 55% (36/65) in CORE. A higher rate of durable response at DL2 was observed in the CORE population, with 6-month ORR and CR of 50% and 50% (7/14), vs 40% (8/20) and 30% (6/20) at DL1. Long term efficacy, including 6-/12-month follow up from ~95/~55 pts, will be reported.
Conclusion
Liso-cel shows durable responses in pts with heavily pretreated R/R DLBCL and trends toward more durable responses at DL2. Observed acute toxicities have been manageable at all DLs tested and long-term safety from the initial cohort will be reported.
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): Adoptive immunotherapy, CD19, DLBCL
Abstract: S800
Type: Oral Presentation
Presentation during EHA23: On Saturday, June 16, 2018 from 11:45 - 12:00
Location: Room A1
Background
Lisocabtagene maraleucel (liso-cel; JCAR017) is a CD19-directed 4-1BB CAR T cell product administered in defined composition at a precise dose of CD8 and CD4 CAR T cells. A multicenter, seamless design pivotal phase 1 trial of liso-cel in R/R B-NHL (NCT02631044) has enrolled.
Aims
Long-term follow up of the initial cohort is presented herein.
Methods
Pts with R/R DLBCL, PMBCL, FL3B, or MCL and adequate organ function are eligible. Treatment includes lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel. Multiple dose levels (DLs) and administration schedules were evaluated; DL2 (108 CAR T cells) was chosen for the pivotal cohort. The FULL dataset includes all pts in the initial DLBCL cohort (DLBCL NOS, PMBCL, FL3B) treated with liso-cel at all DLs; CORE dataset includes only pts meeting inclusion criteria for the pivotal cohort, including DLBCL NOS (de novo or transformed from FL) and high grade lymphoma. Study objectives include safety, PK, and antitumor response.
Results
As of Oct 9, 2017, 91 pts were treated and evaluable for safety, 88 for efficacy. Pt characteristics were previously reported (Abramson ASH 2017). CRS was seen in 35% of pts; a single pt (1%) developed grade 3-4 CRS. Neurotoxicity (NT) developed in 19% of pts including 12% grade 3-4; all but one event resolved at time of data snapshot. Median onset of CRS and NT was 5 and 10 days respectively. Nineteen pts (21%) received tocilizumab and/or dexamethasone. Long term safety, including B cell aplasia, infections, and cytopenias, will be reported.
Best ORR in FULL and CORE was 74% (65/88) and 80% (52/65), respectively; best CR was 52% (46/88) in FULL and 55% (36/65) in CORE. A higher rate of durable response at DL2 was observed in the CORE population, with 6-month ORR and CR of 50% and 50% (7/14), vs 40% (8/20) and 30% (6/20) at DL1. Long term efficacy, including 6-/12-month follow up from ~95/~55 pts, will be reported.
Conclusion
Liso-cel shows durable responses in pts with heavily pretreated R/R DLBCL and trends toward more durable responses at DL2. Observed acute toxicities have been manageable at all DLs tested and long-term safety from the initial cohort will be reported.
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): Adoptive immunotherapy, CD19, DLBCL