A novel “armored” type of chimeric antigen receptor (CAR) T-cell therapy called huCART19-IL18 may prove to be effective in patients with non-Hodgkin lymphoma who do not respond to standard CAR T-cell therapy, according to recent findings from a phase I clinical trial presented by Svoboda et al at the 2024 ASCO Annual Meeting (Abstract 7004).
Background
Although CAR T-cell therapy has revolutionized treatment for patients with hematologic malignancies such as non-Hodgkin lymphoma, many of those who receive the therapy do not experience long-term remission. Among patients whose cancer recurs or becomes resistant after CAR T-cell therapy, the prognosis is often poor.
“By the time we treat [patients] with commercially available [U.S. Food and Drug Administration]-approved CAR T-cell therapies, they’ve already tried at least one other treatment that … didn’t work at all or their lymphoma relapsed, and they’re very hopeful that CAR T-cell therapy—which has made such a difference for so many—will work for them too. If the standard-of-care CAR T-cell therapy doesn’t work for them, it’s incredibly disappointing,” stressed lead study author Jakub Svoboda, MD, Associate Professor of Hematology-Oncology at the Abramson Cancer Center at Penn Medicine.
Researchers revealed that huCART19-IL18 is an anti-CD19 CAR T-cell therapy that was further modified to secrete the proinflammatory cytokine interleukin 18. Preclinical studies demonstrated that the novel therapy may enhance CAR T-cell activity.
“We’ve likened this CAR [T-cell therapy] to an armored truck or tank, because the release of [interleukin 18] further protects the CAR T cells and promotes their ability to attack the cancer cells,” explained senior study author Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the Perelman School of Medicine at the University of Pennsylvania.
Study Methods and Results
In this first-in-human study, the researchers analyzed the efficacy of huCART19-IL18 in 21 patients with non-Hodgkin lymphoma whose cancers were relapsed or had stopped responding to treatment after receiving a commercially available CAR T-cell therapy. The researchers found that the novel CAR T-cell therapy was safe and had a 3-month overall response rate of 80% in 20 of the patients.
They noted the production of huCART19-IL18 uses a process that shortens the manufacturing time for the CAR T cells to 3 days—representing an ability to initiate CAR T-cell therapy quicker than the current 9 to 14 days in patients with aggressive, fast-growing cancers. The shortened manufacturing time may also enhance the potency of the CAR T cells.
The addition of interleukin 18 did not result in any new or unexpected safety concerns beyond the known side effects of CAR T-cell therapy—including cytokine-release syndrome and neurotoxicity, both of which were managed successfully.
As patient follow-up continues, the median overall survival following treatment has not yet been determined. The researchers reported that some of the earliest patients treated have been in remission for 2 years or more.
Conclusions
“While we still have more follow-up to do, it’s gratifying to see so many patients with [non-Hodgkin] lymphoma responding to this novel CAR T-cell [therapy],” Dr. Svoboda concluded.
Disclosure: For full disclosures of the study authors, visit meetings.asco.org.
