Bispecific Chimeric Antigen Receptor Targeting Both CD19 and CD22 T Cell Therapy in Adults with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

2019 ◽  
Author(s):  
Hanren Dai ◽  
Zhiqiang Wu ◽  
Hejin Jia ◽  
Chuan Tong ◽  
Yelei Guo ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Lymphoblastic Leukemia ◽  
Antigen Receptor ◽  
Receptor Targeting ◽  
T Cell Therapy ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals Optimizing Chimeric Antigen Receptor T-Cell Therapy for Adults With Acute Lymphoblastic Leukemia

2020 ◽  
Vol 38 (5) ◽  
pp. 415-422 ◽  
Author(s):  
Noelle V. Frey ◽  
Pamela A. Shaw ◽  
Elizabeth O. Hexner ◽  
Edward Pequignot ◽  
Saar Gill ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Therapeutic Potential ◽  
Lymphoblastic Leukemia ◽  
Antigen Receptor ◽  
High Dose ◽  
T Cell Therapy

PURPOSE The anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel (CTL019) has an 81% response rate in children with relapsed or chemotherapy refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). Cytokine release syndrome (CRS) is a life-threatening treatment-related toxicity that limits the full therapeutic potential in adults. We report outcomes for adults with r/r ALL treated with an optimized CTL019 dosing and CRS management strategy. METHODS Adults with r/r B-cell ALL received CTL019 in 1 of 2 trials. Patients received lymphodepletion followed by CTL019 as either a one-time infusion or fractionated infusions split over 3 days (day 1, 10%; day 2, 30%; day 3, 60%), which allowed for day 2 and day 3 doses to be held for early CRS. Total planned CTL019 dose varied with adaptive protocol modifications in response to efficacy and CRS toxicity. RESULTS Thirty-five adults with r/r ALL received CTL019 in 1 of 3 dosing cohorts. The low-dose cohort (n = 9) received single or fractionated dosing and had manageable toxicity with a 33% complete remission (CR) rate. In the high-dose single infusion cohort, 3 of 6 patients with refractory CRS concurrent with culture-positive sepsis died, and 3 achieved CR. The 20 patients in the high-dose fractionated (HDF) cohort had a 90% CR rate and manageable CRS. The HDF cohort had the highest survival, with a 2-year overall survival of 73% (95% CI, 46% to 88%) and event-free survival of 49.5% (95% CI, 21% to 73%). CONCLUSION Fractionated dosing of CTL019 with intrapatient dose modification optimizes safety without compromising efficacy in adults with r/r ALL.

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