OriCAR-017 — a chimeric antigen receptor (CAR) T-cell therapy targeting G protein-coupled receptor class C group 5 member D (GPRC5D) — showed favorable treatment responses in all patients with relapsed or refractory (R/R) multiple myeloma (MM) in the long-term follow-up of the phase I POLARIS study.1 The results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
“OriCAR-017 showed deep and durable responses in patients with heavily pretreated MM,” said study author Shan Fu, PhD, of the First Affiliated Hospital of Zhejiang University School of Medicine in Hangzhou, China. “OriCAR-017 also showed a favorable safety profile.”
The single-arm, dose-escalation study evaluated the safety, tolerability, and efficacy of OriCAR-017 in patients with MM who had failed standard treatments. Initial results showed early signs of efficacy and favorable safety in these patients.2 These latest data comprise at least two years of follow-up.
The long-term follow-up included 10 patients (median age = 64 years; range = 41-71) with R/R MM (median of 5.5 prior lines). Of the patients, 70% presented with high-risk cytogenetics, 40% with extramedullary disease, and 30% with International Staging System stage III. Prior treatments included B-cell maturation antigen (BCMA) CAR-T cell therapy (50%), anti-CD38 antibodies (20%), and autologous hematopoietic cell transplantation (20%). Patients were administrated a single dose of intravenous OriCAR-017 at 1 × 106 CAR T cells per kg (n=3), 3 × 106 CAR T cells per kg (n=4), or 6 × 106 CAR T cells per kg (n=3).
As of January 16, 2024, all patients had responded to treatment, with 100% achieving an overall response rate; 80% reached a stringent complete response (sCR); and 20% experienced a very good partial response (VGPR). “Of the five patients who had prior BCMA therapy, three achieved sCR, and two achieved VGPR,” Dr. Fu said.
As of January 2024, all patients had responded to treatment, with 100% achieving an overall response rate.
All patients reached measurable residual disease (MRD) negativity at day 28. The median duration of response (DOR) was 10.43 months (95% CI 5.00-17.00), and the median progression-free survival (PFS) was 11.37 months (95% CI 5.93-18.00). The median overall survival was not reached (NR), with seven patients undergoing survival follow-up. Two patients died from COVID-19, and one patient died from disease progression. The high-dose group, of which 67% were previously treated with BCMA CAR-T, reached a median DOR of 17.23 months (95% CI 7.33-NR) and a median PFS of 19.10 months (95% CI 8.30-NR).
For all 10 patients, the rates of grade 1 and grade 2 cytokine release syndrome (CRS) were 90% and 10%, respectively, with a median onset time of two days and a median duration of six days. No grade 3 or greater CRS, immune effector cell-associated neurotoxicity syndrome, dose-limiting toxicities, or serious adverse events occurred.
At higher doses, CAR T cells were detectable nine months after infusion. GPRC5D was expressed on MM cells, “with very limited expression on normal tissue, such as nails or skin,” Dr. Fu said. “Importantly, GPRC5D expression is independent of BCMA expression,” making GPRC5D “an ideal target for MM treatment before or after BCMA-targeted therapy.”
Any conflicts of interest declared by the authors can be found in the original abstract.
References
- Huang H, Hu Y, Zhang M, et al. OriCAR-017, a novel GPRC5D-targeting CAR-T, in patients with relapsed/refractory multiple myeloma: long term follow-up results of phase 1 study (POLARIS). Abstract 7511. Presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting; June 4, 2024; Chicago, Illinois.
- Zhang M, Wei G, Zhou L, et al. GPRC5D CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first-in-human, single-centre, single-arm, phase 1 trial. Lancet Haematol. 2023;10(2):e107-e116.
