Marumo Yoshiaki, Ri Masaki, Ebina Toru, Nakamura Tomoyuki, Oshima Yoshiko, Nakashima Takahiro, Kinoshita Shiori, Suzuki Tomotaka, Narita Tomoko, Sanda Takaomi, Komatsu Hirokazu, Iida Shinsuke
Department of Hematology and Oncology Graduate School of Medical Sciences Nagoya City University Nagoya Aichi Japan.
EJHaem. 2025 May 5;6(3):e70040. doi: 10.1002/jha2.70040. eCollection 2025 Jun.
Chimeric antigen receptor T (CAR-T) cell therapy is effective for relapsed or refractory multiple myeloma (RRMM); however, relapse after the B-cell maturation antigen (BCMA) CAR-T cell therapy is associated with poor outcome. Hence, appropriate biomarkers that can predict the outcome are needed.
Patients who received idecabtagene vicleucel, a BCMA-targeted CAR-T cell therapy, were divided into two groups according to a cut-off value of 180 days for the progression-free survival (PFS) event.
Patients in the short responder group were older at diagnosis, had a shorter time from diagnosis to apheresis, and more frequently had prior bispecific antibody treatment or alkylator-containing chemotherapies, while they received less immunomodulatory drugs-based chemotherapy just prior to apheresis. Apheresis samples collected from the long responder group had significantly higher proportion of CD8-positive naïve or stem cell memory (CCR7CD45RO) or central memory (CCR7CD45RO) T cells. When these two T cell subsets were combined into CCR7-positive CD8 T cells, the patients with high levels of CCR7-positive CD8 T cells showed significantly better PFS.
In the future, our results will help us to select specific patients that are likely to have a more favorable outcome and should contribute to establishing an optimal application strategy for CAR-T cell therapies in RRMM.
嵌合抗原受体T（CAR-T）细胞疗法对复发或难治性多发性骨髓瘤（RRMM）有效；然而，B细胞成熟抗原（BCMA）CAR-T细胞疗法后的复发与不良预后相关。因此，需要能够预测预后的合适生物标志物。
接受靶向BCMA的CAR-T细胞疗法idecabtagene vicleucel的患者，根据无进展生存期（PFS）事件180天的临界值分为两组。
短反应组患者诊断时年龄较大，从诊断到采集的时间较短，更频繁地接受过双特异性抗体治疗或含烷化剂的化疗，而在采集前接受基于免疫调节药物的化疗较少。从长反应组采集的单采样本中，CD8阳性初始或干细胞记忆（CCR7CD45RO）或中央记忆（CCR7CD45RO）T细胞的比例显著更高。当将这两个T细胞亚群合并为CCR7阳性CD8 T细胞时，CCR7阳性CD8 T细胞水平高的患者显示出显著更好的PFS。
未来，我们的结果将有助于我们选择可能有更有利预后的特定患者，并应有助于为RRMM中CAR-T细胞疗法建立最佳应用策略。
