Official websites use. Share sensitive information only on official, secure websites. Corresponding author. 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 z chimeric antigen receptor CAR specific to the CD19 antigen. 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 z CAR T cells in B-ALL and a road map for patient management at centers now contemplating the use of CAR T cell therapy.
T cell therapy with tumor-targeted chimeric antigen receptor CAR โmodified T cells has recently transitioned from the laboratory to the clinic and yielded outcomes that support the tremendous potential of this approach to cancer therapy 1 โ 3. CARs are artificial receptors that redirect antigen specificity, activate T cells, and further enhance T cell function through their costimulatory component 4 , 5. In adults, relapsed B-ALL has a markedly poor prognosis with an expected median survival of less than 6 months 8 , 9.
In this setting of highly chemotherapy-resistant, rapidly progressive disease, therapy with CDtargeted CAR T cells resulted in complete molecular remissions CRm , as assessed by immunoglobulin heavy chain IgH deep sequencing, in five of five treated patients.
Achieving CRm in this chemotherapy-refractory population allowed for subsequent allogeneic stem cell transplants allo-SCT in clinically eligible subjects, the standard of care in adults for this disease after relapse 8. We have now treated an additional 11 patients with relapsed or refractory B-ALL. The clinical outcomes in these CDtargeted CAR T cellโtreated patients confirm the clinical efficacy of this approach seen with our initial results; z CAR T cells induced complete remissions CRs in the vast majority of patients, enabling many to transition to an allo-SCT.
