#China #Shanghai #Multiple Myeloma #IASO Bio #CAR T-Cell

IASO Bio's Revelation on CAR T-Cell Therapy

At the 66th American Society of Hematology (ASH) Annual Meeting in San Diego, IASO Biotherapeutics, a leader in biopharmaceutical innovations, showcased crucial findings from its phase 2 study on Equecabtagene Autoleucel (Eque-cel) for the treatment of relapsed/refractory multiple myeloma (R/RMM). This research emphasizes the significance of CAR T-cell persistence in achieving favorable clinical outcomes.

The core of the findings revealed a compelling relationship between the efficacy-to-target ratio and the clinical outcomes for patients undergoing treatment with Eque-cel. A critical insight provided was the assertion that sustained CAR T-cell persistence is pivotal for effective disease management, independent of baseline levels of soluble B-cell maturation antigen (sBCMA).

Over a median follow-up period of approximately 24.67 months, the study enrolled 107 patients across 14 centers, providing a robust dataset for analysis. Among these, those in sustained remission demonstrated a longer median vector copy number (VCN) duration compared to those who progressed or relapsed, with durations recorded at 12.52 months versus 9.03 months, respectively. The overall efficacy-to-target ratio stood at 1.05, underscoring its importance as a potential biomarker for treatment planning.

Understanding the Significance of the Efficacy-to-Target Ratio

Through this study, the efficacy-to-target ratio emerged as a crucial indicator for predicting progression-free survival (PFS) and time to progression (TTP). Patients with a lower efficacy-to-target ratio faced significantly greater risks of progression—relative hazard ratios were calculated at 3.07 for TTP and 2.3 for PFS, both demonstrating a stark correlation.

Evaluation of baseline characteristics revealed several factors, including previous autologous stem cell transplantation (ASCT) and anti-drug antibodies (ADA), significantly correlated with the persistence of Eque-cel. Notably, only a minority of patients displayed a prolonged neutrophil recovery phenotype, which did not adversely affect VCN duration, indicating a favorable safety profile of the CAR-T therapy.

Perspectives from Key Researchers

Prominent figures in hematology, Professors Lugui Qiu and Chunrui Li, highlighted the importance of this post-hoc analysis in understanding the determinants of long-term efficacy in CAR T-treatment scenarios. They emphasized how targeting a product's enduring effectiveness, rather than being affected by sBCMA levels, can greatly enhance treatment strategies for multiple myeloma.

In an earlier report at ASH 2023, a positive correlation was validated between CAR T-cell persistence and the maintenance of minimal residual disease (MRD) negativity—critical for long-term remission outcomes. The results indicated a median CAR T-cell duration for Eque-cel of 419 days, possibly correlating with a 97.8% MRD negativity rate and a sustained rate of 81.7% at 12 months post-infusion.

Looking Ahead: The Future of CAR T-Cell Therapy

The Chief Medical Officer of IASO Bio, Dr. Jie Chen, expressed confidence in the efficacy and safety of Eque-cel. He confirmed the substantial impact of the efficacy-to-target ratio on disease control in multiple myeloma. IASO Bio is rapidly moving forward with a randomized controlled Phase 3 study of Eque-cel for patients with second- and third-line multiple myeloma, aiming to expand access to this cutting-edge therapy.

In summary, IASO Bio’s findings offer profound insights into the behaviors of CAR T-cell therapies in the management of relapsed/refractory multiple myeloma. The implications of maintaining CAR T-cell persistence provide a promising outlook for future treatment strategies that look to improve patient outcomes significantly.