A risk-adapted approach to using preemptive tocilizumab indicated a clinically meaningful benefit against cytokine release syndrome (CRS) in a new study of pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) being treated with CTL019. Study results were reported in the Journal of Clinical Oncology.

CTL019 is a CD19 chimeric antigen receptor T-cell therapy and carries a risk of CRS. According to the study investigators, a high tumor burden in the bone marrow at baseline may be a risk factor for severe CRS.

In this open-label, prospective study (ClinicalTrials.gov Identifier: NCT02906371), children and young adults who had CD19-positive relapsed/refractory B-ALL were placed into either a low- or high-tumor burden cohort (LTBC or HTBC). LTBC patients had a tumor burden of less than 40%, while HTBC patients had a tumor burden of 40% or greater, as determined through baseline assessment of either a bone marrow biopsy or aspirate. The LTBC consisted of 55 patients, and the HTBC had 15 patients.

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Standard CRS management was given to the LTBC, while HTBC patients were given a dose of tocilizumab upon experiencing a persistent high fever. The incidence of grade 4 CRS was the primary study endpoint, with a clinically meaningful benefit for HTBC patients defined as fewer than 5 of 15 patients in this cohort experiencing grade 4 CRS.

Preemptive tocilizumab was given to all HTBC patients. Grade 4 CRS occurred with an incidence of 3.6% (95% CI, 0.4-13) in the LTBC and an incidence of 27% (95% CI, 8-55) in the HTBC. This reflected a clinically meaningful benefit with tocilizumab in the HTBC.

Best overall response rates were 100% for the LTBC and 87% for the HTBC. Compared with LTBC patients, HTBC patients showed poorer overall survival (P <.001), event-free survival (P =.004), and duration of remission (P <.001).

“In conclusion, we found that preemptive administration of tocilizumab to patients with high tumor burden decreased the expected incidence of severe CRS, meeting the primary endpoint, without compromising the antitumor efficacy or safety of CTL019,” concluded the study investigators in their report.

Disclosures: Multiple authors declare affiliation with or received funding from the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Kadauke S, Myers RM, Li Y, et al. Risk-adapted preemptive tocilizumab to prevent severe cytokine release syndrome after CTL019 for pediatric B-cell acute lymphoblastic leukemia: a prospective clinical trial. J Clin Oncol. Published online January 8, 2021. doi:10.1200/JCO.20.02477