Clinical Summary: 

• Design/Population: This first-in-human phase 1 study evaluated OL-101, a dual-target BCMA/GPRC5D CAR T-cell therapy, in 15 patients with heavily pretreated relapsed or refractory multiple myeloma, including patients with extramedullary disease and prior BCMA- or GPRC5D-directed therapy.
• Key Outcomes: OL-101 demonstrated high response rates, deep MRD-negative remissions, and activity in high-risk subgroups, with a manageable safety profile.
• Clinical Relevance: Dual-target CAR T-cell therapy may help overcome antigen escape and therapeutic resistance in heavily pretreated multiple myeloma.

According to results from an ongoing phase 1 study, OL-101, an investigational dual-target CAR T-cell therapy directed against BCMA and GPRC5D, produced deep responses among heavily pretreated patients with relapsed or refractory multiple myeloma. 

These results were presented by Mingming Zhang, MD, PhD, The First Affiliated Hospital and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China, at the European Hematology Association (EHA) Congress in Stockholm, Sweden. 

In this dose-escalation study, 15 patients who had received at least 3 prior lines of therapy, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 antibody, received a single infusion of OL-101 following lymphodepleting chemotherapy. Dose levels ranged from 1.0 × 10⁶ to 2.0 × 10⁶ CAR T cells/kg using a modified 3+3 design. The primary end point was safety. Key secondary end points included objective response rate (ORR), median time to first response, CAR T expansion, and minimal residual disease (MRD) negativity. 

At a median follow-up of 7.2 months, the most frequently reported grade ≥3 treatment-related adverse events were hematologic toxicities, including grade 4 neutropenia in 66.7% of patients and grade 4 thrombocytopenia in 53.3% of patients. Cytokine release syndrome was reported in all patients, including grade 1/2 events in 73.3% of patients and grade ≥3 events in 26.7% of patients. No cytokine release syndrome-related deaths were reported. Grade 1 immune effector cell-associated neurotoxicity syndrome was reported in 1 patient.

Among 13 efficacy-evaluable patients, the ORR was 100%. Very good partial response or better was achieved in 84.6% of patients, including stringent complete responses in 69.2% of patients. Responses were also observed in difficult-to-treat subgroups. Among patients with extramedullary disease, 83.3% achieved very good partial response or better and 66.7% achieved stringent complete response. Among patients previously treated with BCMA- and/or GPRC5D-directed therapies, 66.7% achieved very good partial response or better and 50% achieved stringent complete response.

Median time to first response was 28 days. All patients achieved MRD negativity at a sensitivity threshold of 10^-5 by next-generation flow cytometry. Robust CAR T-cell expansion was observed across all dose levels.

“OL-101 demonstrates a manageable safety profile and highly compelling preliminary efficacy in heavily pretreated, high-risk [relapsed or refractory multiple myeloma] populations,” concluded Dr Zhang. “The achievement of universal, deep MRD‑negative responses in patients with prior BCMA‑ or GPRC5D‑directed therapy and in those with [extramedullary disease] supports dual‑targeting CAR T strategies to overcome antigen escape and therapeutic resistance.”

Source:

Zhang H, Hu Y, Zhang Y, et al. OL-101, a BCMA/GPRC5D dual-targeting CAR-T, induces deep responses in heavily pretreated advanced myeloma, particularly in patients post BCMA-or GPRC5D-targeted therapy or with extramedullary disease. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-4136.