The 29th Annual Meeting of the European Hematology Association (EHA) was grandly held in Madrid, Spain, from June 13 to 16, 2024. At this EHA conference, a study (S200) by Professors Juan Du and Jing Lu from Shanghai Changzheng Hospital was selected for an oral presentation. This study explored the efficacy and safety of GC012F in the first-line treatment of newly diagnosed high-risk multiple myeloma patients eligible for transplantation. To discuss the study and the treatment of multiple myeloma, "Oncology Frontier - Hematology Frontier" conducted an interview with Professor Jing Lu.

Research Overview

BCMA and CD19 Dual-target Fast CAR-T (GC012F) as First-line Treatment for Newly Diagnosed High-Risk Multiple Myeloma Patients: An Open-label, Single-arm Phase I Study

Newly diagnosed high-risk (HR) multiple myeloma (NDMM) patients generally have poor outcomes with first-line treatments. High-efficacy and safe CAR-T cell therapies may meet the treatment needs of these patients. GC012F is an autologous B-cell maturation antigen (BCMA) and CD19 dual-target CAR-T cell therapy developed on the FasTCAR platform, which allows for rapid production. This reduces the time needed for bridging therapy and, when used in newly diagnosed MM patients, maintains better T-cell viability and sustained CAR-T cell expansion, leading to improved clinical outcomes.

This phase I study explored the efficacy and safety of GC012F as a first-line treatment for HR NDMM patients eligible for transplantation (TE). As of February 27, 2024, the median follow-up was 25.2 months. The objective response rate (ORR) reached 100%, with a stringent complete response (sCR) rate of 95.5%. All patients achieved minimal residual disease (MRD) negativity. The initial data indicate that GC012F induces deep and durable responses in TE HR NDMM patients with manageable safety.

Expert Interview

Oncology Frontier – Hematology Frontier: Your team’s study on GC012F as a first-line treatment for newly diagnosed high-risk multiple myeloma was selected for an oral presentation at this conference. Could you briefly introduce the background and main results of this study?

Professor Jing Lu: Multiple myeloma remains an incurable malignant hematologic tumor. For high-risk newly diagnosed multiple myeloma, traditional chemotherapy and transplantation often fail to achieve deep, lasting remissions and improved prognosis. Given the significant efficacy of GC012F in relapsed and refractory multiple myeloma patients, we conducted this clinical trial to improve the prognosis of high-risk newly diagnosed multiple myeloma patients. Excitingly, the study included 22 high-risk myeloma patients, and those treated with GC012F had a complete response rate of 95%, with all patients achieving MRD negativity, indicating significant disease improvement.

With a median survival currently reaching 25 months, the median progression-free survival (PFS) and duration of response (DOR) have not yet been reached, further confirming the potential of GC012F in delaying disease progression and extending survival while ensuring safety.

Oncology Frontier – Hematology Frontier: The results show significant efficacy for GC012F therapy. Could you share the feedback from patients during treatment and how this therapy impacts their quality of life?

Professor Jing Lu: CAR-T therapy differs from traditional multiple myeloma treatments. Traditional treatments require monthly chemotherapy, including medication and regular injections, necessitating frequent hospital visits and causing prolonged stress for patients. In contrast, CAR-T therapy requires only one injection, followed by maintenance therapy with lenalidomide. This allows patients to return to normal life without the need for chemotherapy, significantly improving their quality of life.

Oncology Frontier – Hematology Frontier: MRD negativity is considered a key indicator of treatment efficacy in multiple myeloma. How do you view the performance of GC012F therapy in achieving MRD negativity, and what is the significance of this for long-term survival and prognosis?

Professor Jing Lu: In this study, we focused on two key points: whether patients achieved MRD negativity and the duration of MRD negativity. These indicators are closely related to long-term survival and prognosis improvement. All 22 patients in this study achieved MRD negativity, with deep MRD negativity precision reaching 10^-6, an excellent result for high-risk multiple myeloma patients. Recently, the U.S. FDA also approved MRD as a surrogate endpoint in multiple myeloma clinical trials to support accelerated approval of new drugs, highlighting the critical role of MRD in evaluating treatment efficacy in multiple myeloma.

Oncology Frontier – Hematology Frontier: How do you foresee the role of dual-target BCMA and CD19 CAR-T therapy in future multiple myeloma treatment strategies? What are your expectations for the further development and application of this therapy?

Professor Jing Lu: CAR-T therapy has made significant breakthroughs in tumor treatment in recent years, especially with single-target BCMA CAR-T therapy, significantly improving outcomes for relapsed and refractory multiple myeloma patients. However, this therapy is not perfect and faces some clinical challenges. Therefore, we have high hopes for dual-target CAR-T therapy. The advantage of dual-target CAR-T therapy is that it can overcome the risk of relapse and resistance caused by antigen loss with single-target CAR-T therapy, reducing the negative impact of antigen loss and improving efficacy.

Moreover, besides BCMA dual-target CAR-T therapy, other targets like BCMA-CD3 and BCMA-CD38/CD3 bispecific and trispecific antibodies are being researched, showing promising results. These combinations suggest more benefits for patients through different target combinations. Among various dual-target CAR-T therapies, BCMA and CD19 CAR-T therapy has shown outstanding efficacy and deep remission results, better than bispecific therapies, with well-verified safety. Therefore, using BCMA/CD19 CAR-T therapy in the early treatment of high-risk myeloma patients is worth trying and expecting.

In conclusion, dual-target CAR-T therapy has great potential and advantages, promising to become an important means of treating hematologic tumors in the future. As research progresses, we have reason to believe this innovative therapy will offer more safe and effective treatment options for patients, improving their survival.