Novartis-Backed Leukemia Investigate Shows 82% Remission with CAR T Cell Therapy
A very innovative, personalized cell-based treatment for a high-risk form of the most common childhood cancer resumes to stir through clinical trials. Pediatric oncologists from Children’s Hospital of Philadelphia (CHOP) reported fresh results using T cell immunotherapy against relapsed or refractory acute lymphoblastic leukemia (ALL).
The physician-scientists introduced 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 ruin the patient’s leukemia cells. The CHOP researchers reported on the very first global, multicenter clinical trial of these cells and on a separate single-center trial, the very 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 youthful adults who had relapsed after previous leukemia therapies, and/or had persistent (refractory) disease.
CHOP pediatric oncologist Stephan A. Grupp, M.D., Ph.D., director of CHOP’s Cancer Immunotherapy Frontier Program, co-moderated the ASH session on advances in immunotherapy for ALL at which these findings were introduced. At this session, he reported results from the very first global, multicenter trial of chimeric antigen receptor (CAR) T cells, of which he is the lead investigator.
This examine, 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 eighty one patients at twenty five centers in the U.S., Canada, Europe, Japan and Australia. Among the fifty patients who have received a single dose of the T cells, designated CTL019 cells, forty one patients (82 percent) had a accomplish 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 very first international clinical trial are similar to what we spotted 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 inbetween Grupp, his colleagues in the Perelman School of Medicine at the University of Pennsylvania led by Carl H. June, M.D., a co-author of the current investigate, and Novartis, the sponsor of the trial.
During the same ASH session, CHOP pediatric oncologist Shannon L. Maude, M.D., Ph.D., introduced findings from a pilot phase one probe of “humanized” CAR T cells in thirty six children and youthfull adults with relapsed and refractory ALL. In this examine, 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 very first to use these humanized CAR T cells, called CTL119 cells. Of the thirty six patients, fourteen 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 twenty two patients in the trial had not received previous CAR T cell treatment.
At one month after treatment, thirty patients displayed a accomplish response, including fifty seven percent of those previously treated with murine CAR T cells, and one hundred percent of the CAR-naive patients. At a median follow-up of seven months, twenty four patients remained in remission. CRS occurred in thirty three 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 patients previously treated with CD19 CAR T cells could react to humanized CTL119.”
In 2012, Novartis acquired sensational rights from Penn to CTL019. Several scientists from Novartis and Penn Medicine are co-authors of the abstracts introduced by Grupp and Maude. Both Grupp and Maude are consultants to Novartis, and Grupp receives research funding from Novartis.