Breaking News
December 17, 2017 - Rural Workers Have Higher Exposures to COPD-Causing Pollutants
December 17, 2017 - Don’t Delay Hip Fracture Surgery. Here’s Why: MedlinePlus Health News
December 17, 2017 - NIH launches HIV prevention trial of long-acting injectable medication in women
December 17, 2017 - Op-Ed: Get Ready for a Tsunami of ECGs
December 17, 2017 - Observation care may save more than thought
December 17, 2017 - Scientists explore effectiveness of action video games to combat dyslexia
December 17, 2017 - Teens Acting Badly? Smog Could Be to Blame
December 17, 2017 - FDA Says ‘Yes’ to Short-Acting Insulin Admelog
December 17, 2017 - Vaping popular among teens; opioid misuse at historic lows
December 17, 2017 - Lower Urinary Symptoms Occur in Almost All Patients with SSc
December 17, 2017 - Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)
December 16, 2017 - Butler Hospital launches international Alzheimer’s disease prevention study
December 16, 2017 - iMedicalApps: Virtual Reality Boosts Self-Confidence for Med Students
December 16, 2017 - Researchers validate five new genes responsible for Amyotrophic Lateral Sclerosis
December 16, 2017 - New genetic analysis of candidiasis reveals surprising fungal sex secrets
December 16, 2017 - New high precision machine-learning model could help accelerate drug discovery
December 16, 2017 - Groundbreaking gene therapy trial brings cure for hemophilia closer
December 16, 2017 - Racial Differences Seen in IgG4 Disease
December 16, 2017 - Treacher Collins Syndrome
December 16, 2017 - New approach to tracking how deadly ‘superbugs’ travel could slow their spread
December 16, 2017 - Muscle paralysis may promote breakdown of bones
December 16, 2017 - WSU scientists create injectable dye to track progression of diseases
December 16, 2017 - Kaiser Permanente delivers clot-busting drugs to stroke patients more than twice as fast as national rates
December 16, 2017 - Some Great Holiday Foods for Weight Loss
December 16, 2017 - Shared Decision-Making Strategies for Lung Ca Screening Get High Marks
December 16, 2017 - Lactic acid bacteria can protect against Influenza A virus, study finds
December 16, 2017 - Cancer immunotherapy’s effectiveness may depend on patient’s genetic makeup
December 16, 2017 - Researchers explore patient-doctor conversations, best practices linked to opioid tapering
December 16, 2017 - ‘Virtual child’ to help professionals learn key techniques to treat children with autism
December 16, 2017 - IU scientists discover way to make drug treatment more successful against malaria
December 16, 2017 - Prostate cancer researchers find significant disparities between two liquid biopsy providers
December 16, 2017 - ED-Diagnosed Lung Ca Patients Worse Off: Clin Onc News Report
December 16, 2017 - Calcium in Urine Test: MedlinePlus Lab Test Information
December 16, 2017 - Pregnancy-related conditions taken together leave moms—and dads—at risk
December 16, 2017 - Research uncovers mechanism implicated in defective function of tumor-associated dendritic cells
December 16, 2017 - OncoBreak: Stubborn Racial Disparities; Paid Medical Leave & Chemo; DIY Gene Tests
December 16, 2017 - Critical link between obesity and diabetes has been identified
December 16, 2017 - Transfusion dependence reduces access to high-quality end-of-life care for leukemia patients
December 16, 2017 - Porvair and Suzhou Tianlong Bio to develop epigenetic analysis technologies
December 16, 2017 - FDA Approves Ixifi (infliximab-qbtx), a Biosimilar to Remicade
December 16, 2017 - Morning Break: Trump to Get Check-Up; Cancerous Transplant; Death Knell for MIPS?
December 16, 2017 - First transcatheter implant for diastolic heart failure successful
December 16, 2017 - ‘Sushi-like’ nanodiscs provide structural snapshots of misfolding proteins
December 16, 2017 - Inherited gene variation may be to blame for poor survival of patients with early-onset breast cancer
December 16, 2017 - Sign-up deadline is Friday, but some people may get extra time
December 16, 2017 - Higher Booze Taxes Might Pay Off for Public Health
December 16, 2017 - Regular Activity in Midlife Spares Joints in Women
December 16, 2017 - Rain May Not Cause Achy Joints After All: MedlinePlus Health News
December 16, 2017 - MedDiet adherence doesn’t affect acute heart failure mortality
December 16, 2017 - HKBU experts develop new generation of smart anti-cancer drug molecules
December 16, 2017 - Chronic Kidney Disease Audit finds wide variations in coding of CKD patients in primary care
December 16, 2017 - Scientists use nanoparticles to fight Mucoviscidosis
December 16, 2017 - Increasing physical activity decreases risk of death from lymphoma
December 16, 2017 - Fear compromises the health, well-being of immigrant families, survey finds
December 16, 2017 - Rejected antibiotic candidate could be worth a second look, research finds
December 16, 2017 - Is Nation on the Right Track to Combat Opioid Crisis?
December 16, 2017 - Arthritis No Longer Just a Disease of the Old: MedlinePlus Health News
December 16, 2017 - Study reveals biology behind why muscle stem cells respond differently to aging or injury
December 16, 2017 - Family members without inherited mutation have increased risk of melanoma
December 16, 2017 - Researchers reveal previously unknown mechanism that inhibits cells’ ability to develop into tumors
December 16, 2017 - Studies highlight potential of fMRI applications to detect, treat epilepsy in children
December 16, 2017 - Active surveillance proposed as first-line approach to manage patients with low-risk PMC of the thyroid
December 16, 2017 - Patients’ life values affect their attendance at medical treatment for pelvic-floor dysfunction
December 16, 2017 - Experts consider hazards of antibiotic resistances to be high
December 16, 2017 - Study finds erectile dysfunction as risk factor for early cardiovascular disease
December 16, 2017 - Amber-tinted glasses may reduce insomnia severity
December 16, 2017 - Arthritis Drug Seen Lowering GvHD Risk
December 16, 2017 - Atoh1, a potential Achilles’ heel of Sonic Hedgehog medulloblastoma
December 15, 2017 - Cornell engineers develop new method to measure vital signs using radio waves
December 15, 2017 - Rutgers studies highlight need for salon clients, workers to protect themselves from health risks
December 15, 2017 - FDA Approves Nucala (mepolizumab) for Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)
December 15, 2017 - Morning Break: CVS Buying Aetna; Uterus Transplant Baby; Your Brain on Drugs, Redux
December 15, 2017 - Social phobia linked to autism and schizophrenia
December 15, 2017 - Timestrip technology helping to prevent missed vaccinations
December 15, 2017 - Researchers win NIH grants for Alzheimer’s research on Amish resilience and rapid onset
December 15, 2017 - Mitochondrial error-correction mechanism essential for energy production of cells
December 15, 2017 - New report reveals steep rise in lung disease admissions to emergency departments during winter
December 15, 2017 - Study finds social stigma as barrier to successful treatment of children with HIV in Ethiopia
December 15, 2017 - Health Tip: Keep Gift-Giving Stress Under Wraps
December 15, 2017 - Long Stoppage of Bisphosphonates Tied to More Fractures
Study provides detailed characterization of neurotoxicity arising from CD19 CAR T-cell therapy

Study provides detailed characterization of neurotoxicity arising from CD19 CAR T-cell therapy

image_pdfDownload PDFimage_print

Bottom Line: New potential biomarkers and a novel algorithm could help identify patients at increased risk of suffering from severe neurotoxicity after receiving CD19 CAR T-cell therapy. The study extensively characterized common and occasionally fatal side effects of this immunotherapy.

Journal in Which the Study was Published: Cancer Discovery, a journal of the American Association for Cancer Research.

Authors: Cameron J. Turtle, MBBS, PhD, associate member at Fred Hutchinson Cancer Research Center, associate professor at the University of Washington, and attending physician on the Immunotherapy Service at Fred Hutch.

Background: On August 30, 2017, the FDA approved the first CD19 CAR T-cell therapy, tisagenlecleucel (Kymriah), for the treatment of acute lymphoblastic leukemia (ALL) in certain pediatric and young adult patients. Different CD19 CAR T-cell therapies are being developed and tested, and reports show that a small number of patients who received certain forms of this therapy in clinical trials have died from severe neurotoxicity.

Turtle and colleagues sought to provide a detailed clinical, radiological, and pathological characterization of neurotoxicity arising from CD19 CAR T-cell therapy.

How the Study Was Conducted: The researchers used data from a clinical trial in which 133 adult patients with relapsed and/or refractory CD19 B-cell ALL, non-Hodgkin lymphoma or chronic lymphocytic leukemia were treated with lymphodepletion chemotherapy followed by infusion of JCAR014, a type of CD19 CAR T-cell therapy developed at Fred Hutchinson Cancer Research Center.

Within 28 days of treatment, 53 patients (40 percent) developed grade 1 or higher neurologic adverse events and of these 28 (21 percent) had grade 3 or higher neurotoxicity; alterations in neurologic status completely resolved in a majority of cases. Four of the 133 patients (3 percent) developed fatal neurotoxicity.

Results: Turtle and colleagues found that patients with an early onset of CRS were at increased risk of subsequently developing severe neurotoxicity. While tocilizumab (Actemra), an IL-6R antagonist approved by the FDA to treat CRS, was effective in ameliorating CRS-related fever and hypotension in most patients, the team found that its role in preventing or treating neurotoxicity is less clear.

Patients who experienced neurotoxicity were mostly younger and had B-cell ALL, higher tumor burden, and more CD19-positive cells in the bone marrow, compared with those who did not develop this side effect. Data also revealed that those with severe neurotoxicity had endothelial activation, which could contribute to manifestations such as capillary leak, blood coagulation abnormalities, and disruption of the blood-brain barrier that were observed in patients with severe CRS and neurotoxicity.

Turtle and colleagues developed a predictive classification tree algorithm based on the side effects, including fever, and high serum IL-6 and MCP-1, to identify patients, within the first 36 hours after CAR T-cell infusion, who are at increased risk for severe neurotoxicity. Patients at increased risk for this adverse event may benefit from early intervention, Turtle noted; however, he pointed out that additional studies are required.

Authors’ Comments: “CD19 CAR T-cell therapy is a highly effective, novel treatment modality that has rapidly expanded in the cancer research and treatment field over the past few years, including recent approval of one form of this therapy by the U.S. Food and Drug Administration [FDA],” said Turtle.

“There is understandably anxiety about some of the side effects of CD19 CAR T-cell therapy, but these treatments have been very effective for a subgroup of patients with resistant disease,” he said. “It is important to understand the side effects, such as cytokine release syndrome [CRS] and neurological toxicity.”

Enormous improvements have been made in the last few years in strategies to minimize the risk of toxicity, Turtle noted. “Because CAR T-cell therapy is so new, we are still learning how to improve the delivery and reduce the side effects,” he added.

Limitations: Limitations of the study include that the characterization of side effects was only from patients who received JCAR014 and not other forms of CD19 CAR T-cell therapies, Turtle said.

Tagged with:

About author

Related Articles