OL-101 is an autologous B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GPRC5D) bispecific dual-targeting CAR T-cell therapy developed for patients with relapsed or refractory multiple myeloma. As a lead cell therapy asset of Overland US, OL-101 represents a next-generation dual-antigen CAR T approach designed to overcome antigen escape and resistance seen with single-target BCMA-directed therapies, while maintaining activity in heavily pretreated and high-risk disease settings. Under the Share Exchange Agreement, Allogene Overland acquired 100% equity in Overland Pharmaceuticals (US), including its research and development and clinical operations. Following completion, Overland Pharmaceuticals (US) became a subsidiary of Allogene Overland (82% ownership).

At EHA 2026, the company presented first-in-human Phase I/II clinical data of OL-101 in multiple myeloma, primarily focusing on patients previously exposed to BCMA or GPRC5D-targeted therapies or those with extramedullary disease (EMD). As of January 2026 data cutoff:

Key Efficacy Highlights:

• Overall response rate (ORR): 100%

• Very good partial response (VGPR) or better: 84.6%

• Stringent complete response (sCR): 69.2%

• High-risk subgroups (Extramedullary disease [n = 6]):

• VGPR or better: 83.3%

• sCR: 66.7%

• Prior BCMA and/or GPRC5D-directed therapy (n = 6):

• VGPR or better: 66.7%

• sCR: 50.0%

• Response kinetics & depth

• Median time to first response: 28 days

• Chimeric antigen receptor T-cell expansion: robust across all dose levels, peak between Days 10–21 post-infusion

• Minimal residual disease (MRD) negativity: 100% of patients (10⁻⁵ sensitivity by next-generation flow cytometry)

Key Safety Highlights:

• CRS observed in all patients:

• Grade 1–2: 73.3%

• Grade ≥3: 26.7%

• No Grade 5 events

• ICANS: 1 patient (Grade 1; ICE score 7 for 1 day)

• Other Grade ≥3 TRAEs (mainly hematologic):

• Grade 4 neutropenia: 66.7%

• Grade 4 thrombocytopenia: 53.3%

KOL insights

“OL-101’s simultaneous targeting of BCMA and GPRC5D represents a rational strategy to overcome one of the key mechanisms of relapse following single-antigen CAR T therapy, namely antigen escape. Early evidence of activity in patients previously exposed to BCMA- or GPRC5D-directed therapies suggests potential biological non-redundancy and clinically meaningful re-sensitization in highly refractory disease.” – Expert Opinion

“The high rates of VGPR or better and stringent complete responses observed in patients with extramedullary disease and extensive prior therapy are particularly noteworthy. These subgroups typically exhibit poor responses to existing therapies, indicating that OL-101 may retain efficacy even in advanced, biologically aggressive multiple myeloma.”– Expert Opinion

Conclusion 

Multiple myeloma is a plasma cell malignancy, with more than 35,000 people living with the disease in the UK and approximately 6,000 new cases diagnosed annually. Although treatment outcomes have improved substantially with immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and T-cell–redirecting therapies, relapse remains inevitable for most patients. The heavily pretreated multiple myeloma segment is increasingly driven by cellular immunotherapies and T-cell–redirecting approaches, particularly CAR-T cell therapies and bispecific antibodies, with physicians often favoring CAR-T therapies because of their ability to induce deep and durable responses. In this evolving landscape, OL-101 has emerged as a promising next-generation dual-targeting CAR-T therapy designed to overcome antigen escape and resistance associated with single-target immunotherapies, demonstrating deep and rapid responses even in patients with prior BCMA/GPRC5D-directed therapy and extramedullary disease. Its encouraging efficacy and manageable CAR-T–consistent safety profile support further development as a potential treatment option for heavily pretreated RRMM.