IASO Bio presented groundbreaking clinical data at the 2024 European Hematology Association Annual Congress demonstrating that Equecabtagene Autoleucel (Eque-cel), the world's first approved fully human CAR-T product, achieved remarkable efficacy in treating high-risk newly diagnosed multiple myeloma patients who are ineligible for transplantation.
Study Design and Patient Population
The FUMANBA-2 study is a multicenter, open-label, phase I, single-arm study led by Professor Lijuan Chen from Jiangsu Province Hospital and Professor Bing Chen from Nanjing Drum Tower Hospital. The study enrolled patients with high-risk newly diagnosed multiple myeloma who completed four cycles of induction treatment before receiving Eque-cel infusion at a dose of 1×10⁶ CAR-T/kg.
As of January 25, 2024, 16 subjects received Eque-cel therapy. The patient population represented particularly challenging cases, with high-risk cytogenetics detected in all subjects, including 62.5% with double-hit and 12.5% with triple-hit abnormalities. Additionally, 25% of subjects had extramedullary disease, and 37.5% had R-ISS stage III disease.
Exceptional Efficacy Results
The study demonstrated unprecedented efficacy outcomes with a median follow-up time of 7.46 months. All subjects achieved minimal residual disease (MRD) negativity, with 71.4% maintaining MRD negativity for more than 12 months. The overall response rate reached 100%, with 93.8% of patients achieving stringent complete response.
The 12-month progression-free survival rate was 84.4%, and the median progression-free survival had not been reached at the time of data cutoff. These results represent a significant advancement in treating this high-risk patient population.
Favorable Safety Profile
Safety analysis revealed a manageable toxicity profile with 68.8% of patients experiencing grade 1-2 cytokine release syndrome. Notably, no grade 3 or higher CRS events were observed, and no immune effector cell-related neurotoxicity syndrome or other neurological toxicities occurred.
The median time of CRS occurrence was the 7th day after infusion, with a median duration of 3 days. The most common grade 3 or above drug-related adverse event was blood cell count reduction, and the incidence of grade 3 or above infectious disease adverse events was 25.0%.
Pharmacokinetics and Biomarker Analysis
Pharmacokinetic analysis showed the median peak time of CAR copy number in peripheral blood was 10 days after infusion, with a median peak level of 79,681.299 copies/μg DNA. Importantly, 81.25% of subjects achieved clearance of free B-cell maturation antigen within one month after infusion, indicating effective target engagement.
Clinical Significance and Expert Commentary
Professor Lijuan Chen emphasized the groundbreaking nature of this research, stating that "this is the world's first report on CAR-T therapy being used as a first-line treatment in this specific patient population." She noted that for newly diagnosed multiple myeloma patients unsuitable for transplantation, CAR-T therapy as first-line treatment is expected to improve remission rates, extend survival, and enhance patient prognosis compared to traditional treatments.
Professor Bing Chen highlighted the particular benefit for high-risk patients, explaining that "high-risk newly diagnosed multiple myeloma patients have a poor prognosis in standard first-line treatment." He noted that compared with relapsed/refractory multiple myeloma patients, the incidence and severity of CRS in high-risk newly diagnosed patients treated with Eque-cel are lower, demonstrating a more favorable safety profile.
Regulatory Status and Future Implications
Equecabtagene Autoleucel has received New Drug Application approval from China's National Medical Products Administration and U.S. FDA IND approval for treating relapsed/refractory multiple myeloma. The company has also received NMPA IND approval for second- and third-line treatment of multiple myeloma.
This study represents a paradigm shift in multiple myeloma treatment, potentially establishing CAR-T therapy as a viable first-line option for high-risk patients ineligible for transplantation, offering new hope for improved outcomes in this challenging patient population.
