Multiple myeloma is one of the most common hematologic malignancies, characterized by marked biological heterogeneity and a complex disease course. Achieving deep and durable remission at initial diagnosis is critical for improving long-term outcomes. At the recent Annual Meeting of the American Society of Hematology (ASH), Professor Du Juan’s study was selected for oral presentation, evaluating the use of dual-target BCMA/CD19 FasTCAR-T therapy as first-line treatment in patients with newly diagnosed multiple myeloma (NDMM). The encouraging results provide strong evidence supporting the earlier use of CAR-T therapy. Hematology Frontier invited Professor Du Juan for an in-depth discussion of the study and future research directions. 

Hematology Frontier: GC012F/AZD0120 demonstrated a 100% overall response rate and a 97% stringent complete response rate in newly diagnosed multiple myeloma, with consistently high MRD-negative rates across multiple time points. In your view, what is the core clinical value of using dual-target FasTCAR-T as first-line therapy, and what does this mean for the current NDMM treatment landscape?

Professor Du Juan: In multiple myeloma, both the initial diagnosis and the first relapse represent critical therapeutic windows. Achieving deeper and more durable responses at diagnosis has a profound impact on long-term prognosis. Among available treatment strategies, immunotherapy—particularly CAR-T cell therapy—has shown the greatest promise, delivering deep and sustained responses in relapsed or refractory disease. Therefore, moving CAR-T therapy earlier into the treatment course is a natural and inevitable direction.

Historically, new therapies are introduced in later lines before being advanced to earlier settings. The data presented this year demonstrate that CAR-T therapy in newly diagnosed patients can achieve exceptionally deep responses, very high response rates, and prolonged remission duration. These findings are highly representative and further support the clinical value of frontline CAR-T therapy in NDMM.

Hematology Frontier: This study uses a dual-target design incorporating both BCMA and CD19, supported by the FasTCAR-T next-day manufacturing platform. Could you elaborate on the mechanistic and clinical innovations of this approach, and how it addresses key limitations of conventional CAR-T therapy in myeloma?

Professor Du Juan: Although single-target CAR-T therapies have achieved impressive efficacy in multiple myeloma, relapse still occurs in a subset of patients. This prompted us to explore strategies that could further deepen responses and prolong remission. Multiple myeloma is highly heterogeneous, and CD19 has been shown to be expressed on myeloma progenitor-like cells. By combining the classical BCMA target with CD19, dual-target CAR-T therapy can eliminate both mature tumor cells and progenitor-like populations, potentially resulting in more sustained disease control. Clinical outcomes from our study support this theoretical advantage in both response depth and durability.

In addition, conventional CAR-T manufacturing typically requires four to six weeks or longer. For both newly diagnosed and relapsed patients, rapid disease control is essential. During prolonged manufacturing periods, bridging therapy is often required, which may increase toxicity and delay definitive treatment. The FasTCAR-T rapid manufacturing platform dramatically shortens production time, improving treatment timeliness and reducing reliance on bridging therapy, thereby offering clear clinical advantages.

Hematology Frontier: Your subgroup analyses showed comparable depth of response between high-risk and standard-risk cytogenetic patients, while patients with extramedullary soft-tissue plasmacytomas had significantly shorter survival. How do you interpret these differences, and should future CAR-T strategies be tailored based on specific risk features?

Professor Du Juan: Precision and individualized treatment are central themes in CAR-T therapy for multiple myeloma. In our study, approximately 80% of patients were considered high-risk, including those with high-risk cytogenetic abnormalities or extramedullary disease. Among these, extramedullary soft-tissue involvement remains particularly challenging. This difficulty stems from an incomplete understanding of the biology of extramedullary disease, which may limit the effectiveness of CAR-T therapy. Furthermore, CAR-T cell infiltration into soft-tissue lesions may be suboptimal, and antigen expression profiles may differ from those in the bone marrow microenvironment.

Nevertheless, as our understanding of myeloma biology deepens and novel targets are identified, these challenges may gradually be overcome. Continued innovation will be essential to further refine CAR-T strategies and improve outcomes in these high-risk subgroups.

Hematology Frontier: With a median follow-up exceeding 30 months and median PFS and OS not yet reached, what are the key future research directions for GC012F/AZD0120? Will efforts focus on larger studies, integration with transplant strategies, maintenance approaches, or expansion into additional myeloma populations?

Professor Du Juan: To date, the median follow-up in newly diagnosed patients has reached 36.5 months, exceeding three years. Moving forward, we plan to conduct global, multicenter clinical studies and perform more detailed analyses in specific patient populations, including those with high-risk cytogenetics, extramedullary disease, transplant-eligible, and transplant-ineligible patients. In the future, randomized controlled trials comparing CAR-T therapy with autologous stem cell transplantation may also be considered.

This progression reflects the natural evolution of any innovative therapy: through rigorous clinical investigation, its role is refined, indications are expanded, and ultimately, more patients can benefit from improved treatment options.