Contributions
Abstract: S143
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 12:00 - 12:15
Location: Room N109
Background
CD19-specific chimeric antigen receptor (CAR) modified T cells produce high anti-tumor activity in relapsed or refractory (R/R) ALL, but can be associated with cytokine release syndrome (CRS) and neurotoxicity (NTX).
Aims
We examined baseline and post-treatment clinical and laboratory parameteres to identify factors associated with severe NTX (≥Grade 3) in our phase I clinical trial of CD19-specific 19-28z CAR T cells for adult patients (pts) with R/R B-ALL (NCT01044069).
Methods
51 adult pts with R/R B-ALL were treated with 19-28z CAR T cells following conditioning chemotherapy at MSKCC. In order to identify clinical and serum biomarkers associated with severe NTX (sNTX), we examined demographic, treatment, and clinical blood parameters as well as in vivo CAR T expansion and serum cytokines, and performed univariate and multivariate analysis.
Results
In this cohort of ALL pts, 20, 8, 2, 18 and 3 pts experienced Gr 0, 1, 2, 3, and 4 NTX, respectively. No pt developed grade 5 NTX and no cerebral edema was seen. Disease burden (≥50% blasts) at the time of T cell infusion (p=0.0045) and post-treatment ≥Gr3 CRS (p=0.0010) were significantly associated with sNTX, but we found no association with age, weight, T cell dose, choice of conditioning chemotherapy (Flu/Cy s. Cy), and prior lines of treatment. Among the clinical and blood parameters, fever, low PLT, high ferritin and MCHC as well as elevated GM-CSF, IFNγ, IL-15, IL-5, IL-10, IL-2 at day 3 of T cell infusion at day 3 of T cell infusion were significantly associated with sNTX (all p<0.01). While some of these cytokines were also elevated in severe CRS cases, IL-5 and IL-2 at day 3 were unique to sNTX. Furthermore, in vivo peak CAR T expansion at day 7 (p=0.0001) significantly correlated with sNTX (p<0.01). Lastly, multivariate analysis revealed baseline PLT <60 or MCHC >33.2% and morphologic disease (>5% blasts) has 95% sensitivity and 70% specificity of identifying sNTX pts.
Conclusion
These data provide a characterization of early clinical and serum biomarkers of sNTX in adult pts receiving 19-28z CAR T cells and should help identify appropriate pts for early intervention strategy to mitigate NTX.
Session topic: 24. Gene therapy, cellular immunotherapy and vaccination
Keyword(s): toxicity, Cellular therapy, CD19, Acute lymphoblastic leukemia
Abstract: S143
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 12:00 - 12:15
Location: Room N109
Background
CD19-specific chimeric antigen receptor (CAR) modified T cells produce high anti-tumor activity in relapsed or refractory (R/R) ALL, but can be associated with cytokine release syndrome (CRS) and neurotoxicity (NTX).
Aims
We examined baseline and post-treatment clinical and laboratory parameteres to identify factors associated with severe NTX (≥Grade 3) in our phase I clinical trial of CD19-specific 19-28z CAR T cells for adult patients (pts) with R/R B-ALL (NCT01044069).
Methods
51 adult pts with R/R B-ALL were treated with 19-28z CAR T cells following conditioning chemotherapy at MSKCC. In order to identify clinical and serum biomarkers associated with severe NTX (sNTX), we examined demographic, treatment, and clinical blood parameters as well as in vivo CAR T expansion and serum cytokines, and performed univariate and multivariate analysis.
Results
In this cohort of ALL pts, 20, 8, 2, 18 and 3 pts experienced Gr 0, 1, 2, 3, and 4 NTX, respectively. No pt developed grade 5 NTX and no cerebral edema was seen. Disease burden (≥50% blasts) at the time of T cell infusion (p=0.0045) and post-treatment ≥Gr3 CRS (p=0.0010) were significantly associated with sNTX, but we found no association with age, weight, T cell dose, choice of conditioning chemotherapy (Flu/Cy s. Cy), and prior lines of treatment. Among the clinical and blood parameters, fever, low PLT, high ferritin and MCHC as well as elevated GM-CSF, IFNγ, IL-15, IL-5, IL-10, IL-2 at day 3 of T cell infusion at day 3 of T cell infusion were significantly associated with sNTX (all p<0.01). While some of these cytokines were also elevated in severe CRS cases, IL-5 and IL-2 at day 3 were unique to sNTX. Furthermore, in vivo peak CAR T expansion at day 7 (p=0.0001) significantly correlated with sNTX (p<0.01). Lastly, multivariate analysis revealed baseline PLT <60 or MCHC >33.2% and morphologic disease (>5% blasts) has 95% sensitivity and 70% specificity of identifying sNTX pts.
Conclusion
These data provide a characterization of early clinical and serum biomarkers of sNTX in adult pts receiving 19-28z CAR T cells and should help identify appropriate pts for early intervention strategy to mitigate NTX.
Session topic: 24. Gene therapy, cellular immunotherapy and vaccination
Keyword(s): toxicity, Cellular therapy, CD19, Acute lymphoblastic leukemia