SAN FRANCISCO—Treatment with chimeric antigen receptor (CAR)-targeting CD19 (CTL019) cells is associated with a significant cytokine release syndrome that quickly responds to interleukin-6-targeted anticytokine treatment, and CTL019 cells can cause strong and durable responses in pediatric patients with relapsed, refractory acute lymphocytic leukemia (ALL), a study presented at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition has shown.

For the pilot study, researchers sought to investigate the outcomes of pediatric patients with relapsed, refractory ALL who received CTL019 therapy.

Researchers lentivirally transduced T cells with a CAR composed of anti-CD19 scFv/4-1BB/CD3ζ, activated/expanded ex-vivo with anti-CD3/anti-CD28 beads, and then administered into pediatric patients with relapsed or refractory CD19+ ALL.

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Of the 39 patients infused with the cells, 92%, achieved a complete response.Of the 10 relapses, five were CD19+ and 5 were CD19-. With a median follow up of 6 months (range 1.5-31), 15 patients experienced remission for 1 year or more, and there were no events after 12 months.

In addition, three patients had gone on to undergo stem cell transplantations. The 6-month event free survival was 70% (95% confidence interval [CI] 56-88) and the 6-month duration of response was 76% (95% CI 61-94).

All responding patients developed grade 1 to 4 cytokine release syndrome (CRS) during peak T-cell expansion, but CRS was “controlled with anti-interleukin-6 therapy, tocilizumab,” said Stephan A. Grupp, MD, PhD, from Children’s Hospital of Philadelphia and the Abramson Cancer Center in Philadelphia, PA, while presenting at the meeting. Analyses showed significant increases of interleukin-6 and interferon-γ.

In addition, “severity was related to tumor burden,” explained Dr. Grupp. Significant confusion and aphasia was also observed, but only in a small number of patients and after CRS, he added.

CTL019 therapy was designated Breakthrough Therapy by the U.S. Food and Drug Administration for both pediatric and adult patients with ALL. Phase 2 trials with CTL019 are currently in process.


Grupp, Stephan, MD, PhD, et al. “380 T Cells Engineered with a Chimeric Antigen Receptor (CAR) Targeting CD19 (CTL019) Have Long Term Persistence and Induce Durable Remissions in Children with Relapsed, Refractory ALL.” ASH 2014. Oral Presentation. December 8, 2014.