Another Win for CAR-T Therapy, Medpage Today
Another Win for CAR-T Therapy
Earn Free CME Credits by reading the latest medical news in your specialty.
Activity Points
MONTREAL – The investigational chimeric antigen receptor T cell (CAR-T) therapy CTL019 induced “potent and durable responses” in children with central jumpy system (CNS) involvement in relapsing/refractory acute lymphoblastic leukemia (ALL), a researcher reported here.
In a secondary analysis of the phase I/IIa CHP nine hundred fifty nine investigate, looking only at children with CNS involvement, 71% remain in finish remission a median of eleven months after the therapy, reported Mala Talekar, MD, from Children’s Hospital of Philadelphia.
Presenting the findings at the annual meeting of the American Society of Pediatric Hematology/Oncology here, Talekar said the “remarkable milestone” underscores the potential for CTL019, a Novartis product that recently received “breakthrough” designation and is undergoing priority review by the FDA.
“Everybody knows that we do a fine job treating freshly diagnosed cases of ALL, standard risk, high risk, or any risk, but when it comes to very first relapse the curve basically plummets down,” said Talekar. “Our best survival rates at very first relapse fall inbetween a dismal 20%-60%, and once a child relapses a 2nd time they fall down to the 10%-20% range.”
The CHP nine hundred fifty nine investigate included sixty children with relapse/refractory CD19-positive ALL who underwent CTL019 CAR-T-cell therapy and were evaluated every three months for relapse in bone marrow and cerebrospinal fluid (CSF).
At 12-months post-infusion, overall survival was 79%, “and even at twenty four months overall survival is somewhere in the range of 65%, which is awesome if you consider the population that is receiving this therapy,” said Talekar. “This population is children who have had two or more relapses or have been refractory to therapy, with the majority being refractory to numerous therapies.”
Overall, the investigate displayed a 93% finish remission rate at day 28, with 100% of patients achieving CNS remission. Cytokine release syndrome was seen in 88% of patients but was only severe in 27%, she reported.
The researchers then determined to concentrate on the subset of seventeen patients whose indication for the therapy was CNS relapse.
“We defined CNS relapse as CNS3 by lumbar puncture or brain or ocular involvement on imaging.”
The number of relapses in this subgroup ranged up to seven, with ten patients having isolated CNS relapse and seven with combined bone marrow/CNS relapse.
“When we very first began enrolling, our eligibility criteria stringently specified either CNS one disease or CNS Two. We were not enrolling CNS three patients because we were not sure whether it was going to be efficacious or what the toxicities were going to be. But as we eyed the trial evolving and that the CTL019 cells were trafficking to the CSF we determined to enroll CNS3 patients as well,” she explained. They enrolled three.
At day twenty eight of follow-up, sixteen of the seventeen patients were staged as CNS1 according to CSF. Among the three patients who were CNS3 before therapy, one was not evaluable due to rapid progression of bone marrow disease, one was in accomplish remission, and the other had initial “pseudo progression” but subsequently accomplish remission at three months.
Of the twelve patients who remain in accomplish remission at 2-3 months post-infusion, five had isolated relapses in marrow but all were CNS negative, said Talekar.
Neurotoxicity with this therapy “is a hot topic right now,” she added. “One would think that patients who have CNS disease would be the ones who had the most toxicity but that did not seem to be the case.”
Among the seventeen CNS patients the rate of Grade three encephalopathy was 18% compared to a 28% rate in the non-CNS patients, and while one patient in each cohort had a grade two seizure, there was also two more patients with Grade three and four seizures in the non-CNS group versus none in the CNS group.
“We did see a broad multiplicity of neurotoxicity symptoms ranging from agitation, ataxia, dizziness, confusion, trigeminal neuralgia, speech disturbance and vision disturbance . but the significant thing to note was all patients were back to their neurologic baseline by month Trio,” she concluded.
Talekar announced she had no relevant financial interests.
