Rare Disease Report

Promising New Treatment Option For Relapsed Acute Lymphoblastic Leukemia

OCTOBER 20, 2014
James Radke

Good news for patients with relapsed acute lymphoblastic leukemia (ALL).  A new study by Maude et al published in the New England Journal of Medicine found patients with multiple relapsed ALL had 90% response rates  following treatment with chimeric antigen receptor T cells targeting CD19.
Chimeric antigen receptors are genetically engineered receptors that can redirect cytotoxic T lymphocytes to cells expressing CD19. The technologies behind the treatment was developed by clinical scientists at University of Pennsylvania. The University has licensed the technology to Novartis Pharmaceutics.
In the study, a total of 30 children and adults with relapsed or refractory ALL were infused with autologous T cells transduced with a CD19-directed chimeric antigen receptor (CTL019) lentiviral vector (0.76x106 to 20.6x106 CTL019 cells / kg). Patients were monitored for a response, toxic effects, and the expansion and persistence of circulating CTL019 T cells.

The study found that complete remission was achieved in 27 patients (90%), including 2 patients with blinatumomab-refractory disease and 15 who had undergone stem-cell transplantation. CTL019 cells proliferated in vivo and were detectable in the blood, bone marrow, and cerebrospinal fluid of patients who had a response.
Sustained remission was achieved with a 6-month event-free survival rate of 67% (95% confidence interval [CI], 51 to 88) and an overall survival rate of 78% (95% CI, 65 to 95).

The study also noted that with a follow-up period of 2 to 24 months, sustained remissions were observed in 19 patients (15 of whom received no further therapy).

All the patients experienced some form of a cytokine-release syndrome within the first few days of the infusion. Most patients (n=22) experienced mild to moderate symptoms (flu-like symptoms, nausea, and muscle pain). Eight patients developed severe cytokine-release syndrome which required treatment for low blood pressure and breathing difficulties. Nine patients were treated with tocilizumab.  All patients fully recovered from the cytokine-release syndrome.
The study’s senior author, Stephan Grupp, MD, PhD, a professor of Pediatrics in Penn’s Perelman School of Medicine and director of Translational Research in the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia said:

“The patients who participated in these trials had relapsed as many as four times, including 60 percent whose cancers came back even after stem cell transplants. Their cancers were so aggressive they had no treatment options left.”

“The durable responses we have observed with CTL019 therapy are unprecedented.”

Novartis Pharmaceutic was granted orphan drug designation for CTL019 in January 2014. In July 2014, it was also granted breakthrough therapy designation.
A larger multicenter study has begun and additional clinicial trials with CTL019 are expected to begin later this year.


 Maude SL, Frey N, Shaw PA, et al. Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. N Engl J Med. 2014;371:1507-1517

Image of ALL smear courtesy wikimedia commons.

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