Researchers show CTL019 cells proliferate and persist

Event-free survival is 70% at 6 months, and 76% of patients had a 6-month duration of response.

Toxicity

Cytokine release syndrome (CRS) is a “significant toxicity,” Dr Grupp said, but investigators are beginning to understand some correlates that impact treatment.

Patients with extraordinary levels of the cytokine interleukin-6 (IL-6)—those who require blood pressure or respiratory support—have significantly more severe CRS than those with lower IL-6 levels (P<0.001). Responding patients have high IL-6 levels as well, but patients with severe CRS have very high levels.

The effector cytokine IFNγ, which may be required for the T-cell response, is also elevated in patients with severe CRS compared to those without CRS (P<0.001).

“The thing that I think we’ve really learned from these patients is the impact of disease burden,” Dr Grupp said.

Patients with high disease burden—those with more than 50% bone marrow blasts—have a high likelihood of developing severe CRS. Patients with less burden—fewer than 50% blasts—have a low likelihood.

Dr Grupp pointed out that only 2 patients with more than 50% blasts did not have severe CRS, and they did not respond to therapy.

“This is highly significant and quite predictive for our patients,” he said, adding that CRS is quite controllable via IL-6 blockade with tocilizumab.

B-cell aplasia is “inevitable” as long as these patients have their CAR T cells, Dr Grupp noted. Patients require IVIg replacement therapy for the entire period.

Macrophage activation syndrome, the flip side of CRS, is also a concern, and neurotoxicity, consisting of confusion and aphasia, occurred in a small number of patients and required no therapy.

Given these results, the investigators believe that CTL019 cells may be able to provide long-term response without subsequent therapy.

CTL019 recently received breakthrough therapy designation from the US Food and Drug Administration.

CTL019 was invented at The University of Pennsylvania but has been licensed to Novartis. Several researchers involved in this study reported research funding and/or consultancy payments from Novartis, and 2 researchers are employed by the company.

*Data in the presentation differ from the abstract.