Currently Viewing:
Newsroom
Currently Reading
The Allen Institute for Immunology Plans Long-term Goal of Mapping the Immune System
December 15, 2018 – David Bai, PharmD
Osteoporosis Working Group Creates Recommendations for Economic Evaluations
December 15, 2018 – Allison Inserro
Federal Judge Strikes Down Affordable Care Act
December 15, 2018 – Allison Inserro and Mary Caffrey
Osteoporosis Screening Strategies Don't Identify Younger Women at Risk
December 14, 2018 – Allison Inserro
Study Determines Why Patients With HIV Have Higher Rates of Cancer
December 14, 2018 – Alison Rodriguez
Sofosbuvir-Based Therapy Safe in Patients With HCV and Certain Cancers
December 14, 2018 – Samantha DiGrande
Gender Differences Found in COPD Hospitalizations and In-Hospital Deaths
December 14, 2018 – Alison Rodriguez
Nontuberculous Mycobacterial Lung Disease Doubled the Risk of Death in a Managed Care Population
December 14, 2018 – Jackie Syrop
What We're Reading: Court Trims Birth Control Rule; Guns as Public Health Issue; California Lenient Toward Doctors
December 14, 2018 – AJMC Staff

Single Resistant Cell Causes Case of Rare ALL Relapse After CAR T Therapy

Allison Inserro
A single leukemia cell was able to reproduce and cause a deadly relapse of pediatric B-cell acute lymphoblastic leukemia (ALL) after it had bonded with the leukemia-targeting chimeric antigen receptor (CAR) lentivirus and infused back into a patient. The case of the cell that became resistant to CAR T-cell therapy was published in the journal Nature Medicine Monday.
A single leukemia cell was able to reproduce and cause a deadly relapse of pediatric B-cell acute lymphoblastic leukemia (ALL) after it had bonded with the leukemia-targeting chimeric antigen receptor (CAR) lentivirus and infused back into a patient. The case of the cell that became resistant to chimeric antigen receptor (CAR) T-cell therapy was published in the journal Nature Medicine Monday.

CAR T-cell therapy modifies patients’ own immune T cells, which are collected and reprogrammed to potentially seek and destroy the patients’ cancer cells. Once they are infused back into patients’ bodies, these newly built cells both multiply and attack, targeting cells that express CD19. 

However, the CAR fused with a single leukemic cell. The presence of the CAR on the leukemic cell may have given that cell the ability to hide from the therapy by masking CD19.  Leukemic cells without CD19 are resistant to CAR T therapy, so this single cell led to the patient’s relapse. 

“In this case, we found that 100 percent of relapsed leukemic cells carried the CAR that we use to genetically modify T cells,” said the study’s lead author Marco Ruella, MD, an assistant professor of hematology-oncology at University of Pennsylvania, in a statement. “This is the first time in hundreds of patients treated at Penn and other institutions that we’ve observed this mechanism of relapse, and it provides important evidence that steps in the delicate and complex process of engineering personalized cells can play a role in patient outcomes.”
The first CAR T-cell therapy to be approved has an indication for ALL.
 The patient, a 20-year-old who received CAR T-cell therapy manufactured by Penn as part of a university-sponsored clinical trial which was completed in 2016, entered the trial with very advanced leukemia that had previously relapsed 3 times. The patient had a complete remission for 9 months before relapsing.


In about 60% of ALL relapses, testing shows cancer cells that do not express CD19. CD19 was also not detectable at relapse in this patient. But in this case, analysis showed the leukemia cells were positive for the CAR protein.

“We learn so much from each patient, in both success or failure of this new therapy, that helps us improve these still-developing treatments so they can benefit more patients,” said J. Joseph Melenhorst, PhD, an associate professor of pathology and laboratory medicine and a member of Penn’s Center for Cellular Immunotherapies. Melenhorst was the senior author on this study as well as the research showing remission from a single cell. “This is a single case, but is still incredibly important and can help us refine the intricate processes required for manufacturing CAR T-cell therapy to ensure the best chance of long-term remissions.”

Penn’s research led to the approval of tisagenlecleucel (Kymriah), sold by Novartis. The FDA approved tisagenlecleucel in August 2017 for the treatment of relapsed or refractory pediatric and young adult patients with B-cell precursor ALL. It is also approved for treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)—the most common form of non-Hodgkin’s lymphoma—as well as high grade B-cell lymphoma and DLBCL arising from follicular lymphoma.

The other approved CAR T therapy is axicabtagene ciloleucel (Yescarta)—Kite Pharma/Gilead’s treatment for adult patients with relapsed or refractory large B-cell lymphoma.

Related Articles

Case Study Identifies New Trigger for CAR-T Cell Expansion in DLBCL in JCAR017 Trial
5 Significant Developments With CAR-T Therapy
Companies Continue to Face Challenges With Developing CAR-T Treatment
UK Knocks Down Yescarta as CAR T Therapy Gains European Authorization
NCCN Report on CAR T-Cell Therapy, Recommendations for Future Use
 
Copyright AJMC 2006-2018 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
x
Welcome the the new and improved AJMC.com, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up
×

Sign In

Not a member? Sign up now!