Personalized therapy achieved complete remission in 90% of leukemia patients

15 Oct 2014

90% of children and adults with acute lymphoblastic leukemia (ALL) who had relapsed multiple times or failed to respond to standard therapies went into remission after receiving an investigational personalized cellular therapy.

The therapy is called CTL019, and is being developed at the Perelman School of Medicine at the University of Pennsylvania. The results are published in The New England Journal of Medicine.


Small number of patients but promising results

The new data include results from the first 25 children and young adults (ages 5 to 22) treated at the Children's Hospital of Philadelphia and first five adults (ages 26 to 60) treated at the Hospital of the University of Pennsylvania.

27 of the 30 patients in the studies achieved a complete remission after receiving an infusion of these engineered "hunter" cells, and 78% of the patients were alive six months after treatment.


"The patients who participated in these trials had relapsed as many as four times, including 60% whose cancers came back even after stem cell transplants. Their cancers were so aggressive they had no treatment options left," said 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. "The durable responses we have observed with CTL019 therapy are unprecedented."

Shannon Maude, MD, PhD, an assistant professor of Pediatrics and a pediatric oncologist at CHOP, and Noelle Frey, MD, MSCE, an assistant professor of Medicine and an oncologist at Penn's Abramson's Cancer Center, are co-first authors of the new study. The research team is led by Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in the Abramson Cancer Center, along with David Porter, MD, the Jodi Fisher Horowitz Professor in Leukemia Care Excellence and director of Blood and Marrow Transplantation in the Abramson Cancer Center.

Patients in the study: how are they doing?

Nineteen patients in the study remain in remission, 15 with this therapy alone, including a 9 year old who was the first ALL patient to receive the therapy more than two years ago. The follow-up periods reported in the study are more than six months for most patients, with a range from 1.4 to 24 months. Five patients went off-study for alternate therapy, three of whom proceeded to allogeneic stem cell transplants while in remission. Seven patients relapsed, between 6 weeks and 8.5 months after their infusions, including three whose cancers returned as CD19-negative leukemia that would not have been targeted by the modified cells.

All patients who received the CTL019 "hunter" cells experienced a cytokine release syndrome (CRS) within a few days after receiving their infusions -- a key indicator that the engineered cells have begun proliferating and killing tumor cells in the body.

During this time:

  • 22 of 30 patients experienced mild to moderate CRS, which included varying degrees of flu-like symptoms, with high fevers, nausea, and muscle pain.
  • 8 patients developed severe CRS, which required treatment for low blood pressure and breathing difficulties.
  • 9 patients were treated with tocilizumab, an immunosuppressant drug that blocks the effects of the inflammatory cytokine IL-6, which have been found to spike during the most robust phase of the engineered cells' expansion in the body.
  • 6 patients also received short courses of steroids to combat CRS symptoms.

All patients on these studies fully recovered from the CRS.

Details on the personalized treatment that "can produce long-lasting remissions"

Tests of all patients who experienced complete remissions also showed that their normal, non-cancerous B cells, which also express the CD19 protein, had been eliminated along with their tumors. The researchers note that persistent absence of normal B cells following CTL019 treatment indicates continued activity of the gene-modified T cells, which are thought to provide long-term, vaccine-like activity preventing tumor recurrence. Since B cells play a role in helping fight infection, patients typically receive immunoglobulin replacement to maintain healthy immune function.

"Our results support that CTL019 can produce long-lasting remissions for certain heavily pre-treated ALL patients without further therapy," Frey said. "For our patients who have already relapsed after stem cell transplants, or don't have any options for donors, this option has provided new hope."

Breakthrough Therapy designation for the treatment of relapsed and refractory adult and pediatric ALL

In July 2014, the U.S. Food and Drug Administration granted CTL019 its Breakthrough Therapy designation for the treatment of relapsed and refractory adult and pediatric ALL, a step which is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions, if a therapy has demonstrated substantial advantages over available treatments. CTL019 is the first personalized cellular therapy to receive the designation. The first multicenter CTL019 trial has recently opened in the U.S., and additional multisite trials are expected to initiate by the end of the year.


Source: Science Daily

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