CAR T cell immunotherapy continues to yield complete responses in leukemia

December 5, 2016, Children's Hospital of Philadelphia
Stephan A. Grupp, M.D., Ph.D., is the director of the Cancer Immunotherapy Frontier Program at Children's Hospital of Philadelphia. Credit: Children's Hospital of Philadelphia

A highly innovative, personalized cell-based treatment for a high-risk form of the most common childhood cancer continues to move through clinical trials. Pediatric oncologists from Children's Hospital of Philadelphia (CHOP) today reported new results using T cell immunotherapy against relapsed or refractory acute lymphoblastic leukemia (ALL).

The physician-scientists presented findings at the annual meeting of the American Society of Hematology today in San Diego.

This immunotherapy modifies a patient's own immune T cells, extracted and engineered to potentially seek and destroy the patient's leukemia cells. The CHOP researchers reported on the first global, multicenter clinical trial of these cells and on a separate single-center trial, the first to use a version of these cells carrying a "humanized" protein more similar to human proteins.

In both trials, the patients were children and young adults who had relapsed after previous leukemia therapies, and/or had persistent (refractory) disease.

CHOP pediatric oncologist Stephan A. Grupp, MD, PhD, director of CHOP's Cancer Immunotherapy Frontier Program, co-moderated the ASH session on advances in immunotherapy for ALL at which these findings were presented. At this session, he reported results from the first global, multicenter trial of chimeric antigen receptor (CAR) T cells, of which he is the lead investigator.

This study, sponsored by Novartis, is a global registration trial—one that will provide data to submit to the U.S. Food and Drug Administration (FDA), requesting approval for clinical use. It has enrolled 81 patients at 25 centers in the U.S., Canada, Europe, Japan and Australia. Among the 50 patients who have received a single dose of the T cells, designated CTL019 cells, 41 patients (82 percent) had a complete response (that is, no detectable leukemia cells) within one to three months after treatment.

As in previous, single-center trials, the immunotherapy stimulated a sometimes severe side effect called cytokine release syndrome (CRS), which the researchers successfully managed, following an existing protocol. CRS can present as a flu-like illness with high fever and muscle aches, and can extend to requiring ICU-level care.

"Our results in this first international clinical trial are similar to what we saw in our single-center trials—in both the safety profile and high levels of effectiveness," said Grupp. Novartis aims to apply for FDA approval in 2017.

The research reflects an ongoing collaboration between Grupp, his colleagues in the Perelman School of Medicine at the University of Pennsylvania led by Carl H. June, MD, a co-author of the current study, and Novartis, the sponsor of the trial.

During the same ASH session, CHOP pediatric oncologist Shannon L. Maude, MD, PhD, presented findings from a pilot phase 1 study of "humanized" CAR T cells in 36 children and young adults with relapsed and refractory ALL. In this study, researchers modified CAR T cells to carry a CAR protein more similar to human protein than is the murine (mouse) protein used in CTL019 and other CD19-targeted CAR T cell treatments.

This trial, conducted at CHOP, is the first to use these humanized CAR T cells, called CTL119 cells. Of the 36 patients, 14 had previously been treated with murine CAR T cells. Some had shown no response, some relapsed after an initial response, and in some the CAR T cells did not persist well. Another 22 patients in the trial had not received previous CAR T cell treatment.

At one month after treatment, 30 patients showed a complete response, including 57 percent of those previously treated with murine CAR T cells, and 100 percent of the CAR-naive patients. At a median follow-up of seven months, 24 patients remained in remission. CRS occurred in 33 patients, but was mild in most patients, and was successfully managed in all.

"These CTL119 results are consistent with the high remission rates we have seen with CTL019," said Maude. "It is also encouraging that previously treated with CD19 CAR T could respond to humanized CTL119."

In 2012, Novartis acquired exclusive rights from Penn to CTL019. Several scientists from Novartis and Penn Medicine are co-authors of the abstracts presented by Grupp and Maude. Both Grupp and Maude are consultants to Novartis, and Grupp receives research funding from Novartis.

Explore further: Benefits persist in T cell therapy for children with relapsed leukemia

Related Stories

Benefits persist in T cell therapy for children with relapsed leukemia

December 6, 2014
An innovative cell therapy against a highly aggressive form of acute lymphoblastic leukemia (ALL) continues to show highly promising results in children treated in a pilot study. Ninety-two percent of the 39 children receiving ...

High response rates, long-term remissions in Penn trials of personalized cell therapy

December 7, 2015
Ninety-three percent of pediatric patients (55 of 59) with relapsed/refractory acute lymphoblastic leukemia (ALL) went into remission after receiving an investigational therapy made from their own immune cells, with continuous ...

T cell immunotherapy: Promising results in children and adults with leukemia

December 7, 2013
Nearly 90 percent of children and adults with a highly aggressive form of acute lymphoblastic leukemia (ALL) showed no evidence of cancer after receiving a novel, personalized cell therapy that reprograms a patient's immune ...

Engineered immune cells produce complete response in child with an aggressive pediatric leukemia

December 9, 2012
By reprogramming a 7-year-old girl's own immune cells to attack an aggressive form of childhood leukemia, a pediatric oncologist has achieved a complete response in his patient, who faced grim prospects when she relapsed ...

CD19-targeting CAR T-cell immunotherapy yields high responses in treatment-resistant CLL

December 3, 2016
In a small, early phase trial, a high percentage of patients who had exhausted most traditional treatments for chronic lymphocytic leukemia saw their tumors shrink or even disappear after an infusion of a highly targeted, ...

Studies of personalized cell therapies define optimal doses

June 3, 2016
More precise dosing methods and cellular engineering techniques show promise in the effort to improve treatment of aggressive cancers with personalized cellular therapies, according to new studies from researchers in the ...

Recommended for you

'Hijacker' drives cancer in some patients with high-risk neuroblastoma

January 23, 2018
Researchers have identified mechanisms that drive about 10 percent of high-risk neuroblastoma cases and have used a new approach to show how the cancer genome "hijacks" DNA that regulates other genes. The resulting insights ...

Enzyme inhibitor combined with chemotherapy delays glioblastoma growth

January 23, 2018
In animal experiments, a human-derived glioblastoma significantly regressed when treated with the combination of an experimental enzyme inhibitor and the standard glioblastoma chemotherapy drug, temozolomide.

Scientists block the siren call of two aggressive cancers

January 23, 2018
Aggressive cancers like glioblastoma and metastatic breast cancer have in common a siren call that beckons the bone marrow to send along whatever the tumors need to survive and thrive.

Researchers identify a protein that keeps metastatic breast cancer cells dormant

January 23, 2018
A study headed by ICREA researcher Roger Gomis at the Institute for Research in Biomedicine (IRB Barcelona) has identified the genes involved in the latent asymptomatic state of breast cancer metastases. The work sheds light ...

Workouts may boost life span after breast cancer

January 22, 2018
(HealthDay)—Longer survival after breast cancer may be as simple as staying fit, new research shows.

Boosting cancer therapy with cross-dressed immune cells

January 22, 2018
Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. The study is published in Nature Methods.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.