TY - JOUR
T1 - Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia
AU - Davila, Marco L.
AU - Riviere, Isabelle
AU - Wang, Xiuyan
AU - Bartido, Shirley
AU - Park, Jae
AU - Curran, Kevin
AU - Chung, Stephen S.
AU - Stefanski, Jolanta
AU - Borquez-Ojeda, Oriana
AU - Olszewska, Malgorzata
AU - Qu, Jinrong
AU - Wasielewska, Teresa
AU - He, Qing
AU - Fink, Mitsu
AU - Shinglot, Himaly
AU - Youssif, Maher
AU - Satter, Mark
AU - Wang, Yongzeng
AU - Hosey, James
AU - Quintanilla, Hilda
AU - Halton, Elizabeth
AU - Bernal, Yvette
AU - Bouhassira, Diana C.G.
AU - Arcila, Maria E.
AU - Gonen, Mithat
AU - Roboz, Gail J.
AU - Maslak, Peter
AU - Douer, Dan
AU - Frattini, Mark G.
AU - Giralt, Sergio
AU - Sadelain, Michel
AU - Brentjens, Renier
PY - 2014/2/19
Y1 - 2014/2/19
N2 - We report on 16 patients with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL) that we treated with autologous T cells expressing the 19-28z chimeric antigen receptor (CAR) specific to the CD19 antigen. The overall complete response rate was 88%, which allowed us to transition most of these patients to a standard-of-care allogeneic hematopoietic stem cell transplant (allo-SCT). This therapy was as effective in high-risk patients with Philadelphia chromosome-positive (Ph+) disease as in those with relapsed disease after previous allo-SCT. Through systematic analysis of clinical data and serum cytokine levels over the first 21 days after T cell infusion, we have defined diagnostic criteria for a severe cytokine release syndrome (sCRS), with the goal of better identifying the subset of patients who will likely require therapeutic intervention with corticosteroids or interleukin-6 receptor blockade to curb the sCRS. Additionally, we found that serum C-reactive protein, a readily available laboratory study, can serve as a reliable indicator for the severity of the CRS. Together, our data provide strong support for conducting a multicenter phase 2 study to further evaluate 19-28z CAR T cells in B-ALL and a road map for patient management at centers now contemplating the use of CAR T cell therapy.
AB - We report on 16 patients with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL) that we treated with autologous T cells expressing the 19-28z chimeric antigen receptor (CAR) specific to the CD19 antigen. The overall complete response rate was 88%, which allowed us to transition most of these patients to a standard-of-care allogeneic hematopoietic stem cell transplant (allo-SCT). This therapy was as effective in high-risk patients with Philadelphia chromosome-positive (Ph+) disease as in those with relapsed disease after previous allo-SCT. Through systematic analysis of clinical data and serum cytokine levels over the first 21 days after T cell infusion, we have defined diagnostic criteria for a severe cytokine release syndrome (sCRS), with the goal of better identifying the subset of patients who will likely require therapeutic intervention with corticosteroids or interleukin-6 receptor blockade to curb the sCRS. Additionally, we found that serum C-reactive protein, a readily available laboratory study, can serve as a reliable indicator for the severity of the CRS. Together, our data provide strong support for conducting a multicenter phase 2 study to further evaluate 19-28z CAR T cells in B-ALL and a road map for patient management at centers now contemplating the use of CAR T cell therapy.
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U2 - 10.1126/scitranslmed.3008226
DO - 10.1126/scitranslmed.3008226
M3 - Article
C2 - 24553386
AN - SCOPUS:84896335556
SN - 1946-6234
VL - 6
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 224
M1 - 224ra25
ER -