A CAR-T therapy trial in ten patients has shown “impressive efficacy” in patients with multiple myeloma, according to the study’s doctors. Researchers carried out the study at the Zhejiang University School of Medicine in China. The trial was carried out to judge the safety and efficacy of the experimental treatment in patients with multiple myeloma, including some who had received previous gene therapy treatments for their illnesses.
CAR-T stands for “chimeric antigen receptor T-Cell.” The gene-edited CAR-T therapy cells used in the Zhejiang study were developed by Oricell Therapeutics. OriCAR-017 was given to the ten patients in the study, which concluded in April of 2022, which resulted in a manageable safety profile.
Oricell has developed a second-generation CAR-T therapy in this instance, which targets a G-protein coupled receptor. GPRC5D is highly expressive in myeloma cells in bone marrow, while only marginally affecting other tissues like hair and nails (hard keratinized tissues).
The trial carried out in Zhejiang was named POLARIS. Patients enrolled in the study had to have confirmed GPRC5D expression in their bone marrow cells or in tumor tissue. Half of the patients had also previously been enrolled in B-cell maturation antigen therapy.
All patients first underwent lymphodilating chemotherapy before receiving an infusion of OriCAR-17. Three dose levels were administered to the patients:
- 1 x 106 cells per kilogram
- 3 x 106 cells per kilogram
- 6 x 106 cells per kilogram
Five men and five women participated in the study. They were between the ages of 41 and 71, with a median age of 64. Each patient had been through anywhere from three to 17 previous lines of therapy. The primary endpoints for the study were safety and tolerability of OriCAR-17, with efficacy being a secondary endpoint.
One of the key findings from the study was that there were no dose-limiting toxicities found. All patients experienced platelet deficiency, a reduction of white blood cells, and reduced neutrophils in the blood. Most also experienced Grade 3 or Grade 4 anemia. All of the patients also experienced cytokene release syndrome, although none of the cases reached Grade 3 or higher. Most importantly, however, none of the patients experienced treatment-related neurotoxicity.
As far as efficacy, every patient receiving CAR-T therapy in the study had an objective response to it. Six of the patients became cancer free with complete response or stringent complete response. Three patients experienced a very good partial response, and one had a partial response. In other words, every single patient experienced at least some level of relief from their multiple myelomas, if not a complete cessation of cancer.
All five of the patients who had previously received B-cell maturation antigen therapy experienced a positive response to the CAR-T therapy. Two experienced a stringent complete response, two had very good partial responses and one had a partial response.
28 days after the patients received CAR-T infusion, they were tested to determine whether cancer cells were present in the form of minimal residual disease-negative response. Their bone marrow flow cytometry was tested, and no cancer cells were found to be present.
The findings of the Zhejiang study conclude that the CAR-T therapy treatment is potentially highly effective against multiple myeloma. The therapy also has a positive safety profile at this point. Scientists have not announced when Phase 2 trials will begin.