Severe Cytokine Release Syndrome Is Associated with Impaired Hematopoietic Recovery after CD19-Targeted CAR-T Cell Therapy

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.3229-3229
• Main Authors: Juluri, Krishna R., Hirayama, Alexandre V., Mullane, Erin, Cleary, Nancy, Wu, Qian Vicky, Maloney, David G., Turtle, Cameron J., Bar, Merav, Gauthier, Jordan
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-126922

Background Chimeric antigen receptor therapy (CAR-T) directed against CD19 has demonstrated efficacy in patients with relapsed/refractory (R/R) B-cell malignancies. Delayed hematopoietic recovery with grade 3/4 neutropenia and thrombocytopenia, requiring extended growth factor administration or transfusions, has been observed in patients undergoing CAR-T cell therapy, although the factors influencing recovery are poorly understood. In this study, we performed multivariable analyses to identify factors associated with hematopoietic recovery in patients undergoing CD19 CAR-T cell therapy. Methods We retrospectively analyzed 125 patients with R/R acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL), treated with CD19-targeted CAR-T cells on a phase 1/2 clinical trial in our institution (NCT01865617). Patients receiving more than one CAR-T infusion were excluded. Criteria for neutropenia, thrombocytopenia, and recovery were defined as per the Center for International Blood and Marrow Transplant Research (CIBMTR) reporting guidelines: neutropenia, absolute neutrophil count (ANC) ≤ 500/mm3; thrombocytopenia, platelet (Plt) count ≤ 20 x 109/L; neutrophil recovery, ANC > 0.5 x 109/L for three consecutive laboratory values obtained on different days irrespective of growth factor administration; platelet recovery, Plt > 20 x 109/L for three consecutive values obtained on different days in the absence of platelet transfusion for seven days. For competing risk analysis, an event was defined as having achieved ANC or Plt recovery, with the following considered as competing events: death, new cytotoxic therapy, relapse with marrow involvement in the absence of ANC or platelet recovery. Patients who never met the CIBMTR criteria for neutropenia of thrombocytopenia were considered as having recovered at time = 0. To identify factors associated with impaired hematopoietic recovery after CD19 CAR-T cell therapy, patient-, disease- and CAR-T cell therapy-related variables were included in a multivariable Fine and Gray model prior to variable selection using LASSO penalization (Table 2 footnote). Results We included 125 patients (ALL, n=44; CLL, n=37; NHL, n=44) with a median age of 55 (range, 20-76). Patients were heavily pre-treated with a median of 4 prior therapies (range, 1-10); 31% had undergone prior autologous or allogeneic hematopoietic cell transplantation (HCT). Median ANC and Plt prior to lymphodepletion were 2 x 1