Major development in re-treatment with CAR T therapy

At the American Society of Hematology (ASH) Annual Meeting in 2022 (Abstract 2016), researchers from the Abramson Cancer Center at the University of Pennsylvania presented preliminary findings from an ongoing Phase I clinical trial demonstrating effective re-treatment with CAR T cell therapy for patients whose cancers relapsed after prior CAR T therapy.

Over the past ten years, CAR T therapies have transformed the way that blood cancer is treated, giving hope to patients who have exhausted all other forms of therapy. However, patients whose cancers recur or stop responding to CAR T therapy have few other treatment options.

In the first-in-human study (NCT04684563), non-Hodgkin lymphoma (NHL) patients who had previously failed CAR T therapy were evaluated for the efficacy of a novel fourth-generation CAR T therapy.

The research represents the initial clinical test using anti-CD19 CAR T cells that secrete interleukin 18 (IL 18) in the United States. According to preliminary findings, this combination approach is safe and did not lead to any additional side effects over other commercially available CAR T therapies.

We designed an ‘armored’ CAR that secretes IL18 and tested it in mice, where we found it to have potent antitumor efficacy in our preclinical studies.”

Carl June, MD, Richard W. Vague Professor, Immunotherapy, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania

All of the first seven patients to receive huCART19-IL18 responded to the treatment, including those who had previously relapsed after receiving commercial CAR T cell therapies or did not respond to them (four patients had a complete response and three patients had a partial response).

None of the four patients whose cancers had completely responded to treatment at month three have experienced a relapse of the condition, and all patients are still alive at a median follow-up of eight months.

Patients whose cancers don’t respond or become refractory to CAR T therapy tend to have poor outcomes, so we are very motivated to find new options for them. Although these are preliminary results, it is encouraging to see how well these patients have done.  Our team at Penn is very excited about this ongoing project and these early results continue to motivate us.”

Jakub Svoboda, MD, Study Lead Author and Associate Professor, Hematology-Oncology, University of Pennsylvania

Patients with CD19+ NHL or CLL that had relapsed or been resistant to at least two lines of therapy, including CAR T therapy, were enrolled in the study. Up until the ideal dose is identified, patients will be enrolled one at a time as the study continues to increase the dose of huCART19-IL18.

The toxicities associated with huCART19-IL18 were transient and resembled those that have been noted with other CAR T products. Four patients experienced cytokine release syndrome and two experienced neurotoxicity. There have not been any fatal study-related incidents or grade-four adverse events.

Notably, huCART19-IL18 can be prepared for administration more quickly than CAR T products with a typical manufacturing time of nine to fourteen days, which is crucial for patients with aggressive, rapidly progressing diseases. A previous preclinical study discovered that the T cells’ potency could be increased by quicker manufacturing time.

In a poster session held in Hall D on Saturday, December 10^th. 2022 from 5:30 to 7:30 p.m. CT, Svoboda presented the abstract.