Point-of-care CAR-T shows ‘promising’ efficacy, safety for B-cell non-Hodgkin lymphoma
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Early phase 1 trial results using a novel chimeric antigen receptor T-cell therapy manufactured at University of Colorado show encouraging efficacy for adults with relapsed or refractory B-cell non-Hodgkin lymphoma.
Data presented at American Association for Cancer Research Annual Meeting revealed that six of seven patients had an initial complete response to the investigational cell therapy and remain alive as of the study’s data cutoff date.
Background
Developing a new CD19-directed CAR-T for patients with B-cell non-Hodgkin lymphoma is necessary despite an already crowded market of commercially available therapies because approximately 60% of patients who receive the therapy lack a durable response and will experience disease relapse, according to Manali Kamdar, MD, associate professor of medicine/hematology at University of Colorado School of Medicine and clinical director of lymphoma services at CU Cancer Center.
Another issue with commercially available CAR T cells is the amount of time they take to manufacture, which can last from weeks to up to a month or more and prevent many patients from receiving the therapy, she added.
“Researchers are really trying to look for better CAR-T constructs with the ability to deliver treatments faster to patients who need it,” she told Healio. “Our goal was to hopefully design a better product in terms of efficacy and toxicity, but — most importantly — also do something local at the University of Colorado to make sure that the manufacturing time decreases so we can get patients enrolled and treated faster to get the full benefit of the products.
Kamdar and colleagues used a novel CD19-directed CAR T-cell therapy developed at University of Colorado Anschutz Medical Campus and manufactured on site using the CliniMACS Prodigy (Miltenyi Biotec) automated cell processing system.
The entire process from apheresis to infusion of the final cell product takes 2 weeks, Kamdar said.
Methodology
Seven patients (median age 61 years; range, 45-79) with relapsed or refractory large B-cell lymphoma received treatment in the study. Histology subtypes included marginal zone lymphoma (n = 1), follicular lymphoma grade IIIA (n = 1), transformed lymphoma (n = 3), low-grade follicular lymphoma (n = 1) and diffuse large B-cell lymphoma (n = 1).
Patients received lymphodepleting chemotherapy followed by a single infusion of CD19-directed CAR-T at an average dose of 1.2 ± 0.2 × 108 cells. Two patients received out-of-spec CAR-T that had transduction efficiency of less than 20%.
Median follow-up was 12 months.
Key results
Safety data showed that two patients experienced grade 2 treatment-related cytokine release syndrome. One of those patients also had grade 2 neurotoxicity — the only reported case of neurotoxicity during the study.
One patient experienced dose-limiting toxicity, whereas the two patients who received out-of-spec products did not show any additional safety issues.
Efficacy results showed a compete metabolic response for six of seven patients during a follow-up scan at 3 months after infusion, including the two patients who received out-of-spec products.
One patient died before their first post-infusion evaluation. Another patient experienced disease progression when being evaluated during a scan 6 months after infusion. The remaining five patients are still in remission as of the study’s data cutoff date.
Clinical implications
Kamdar said the CAR-T product in this trial shows “a promising safety and efficacy profile.” Her group continues to enroll more patients and plans on presenting longer-term follow-up results at future major meetings.
“The signals we are seeing with our product are certainly very encouraging,” she told Healio. “I hope to see this trend continue as we treat more patients.”
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Kamdar M, et al. Abstract CT522. Presented at: American Association for Cancer Research Annual Meeting; April 8-13, 2022; New Orleans.
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