Low platelet counts and low CD4/CD8 ratios at apheresis increase the risk of CAR T-cell manufacturing failure in myeloma

Blood Neoplasia Pub Date : 2025-02-01 DOI:10.1016/j.bneo.2024.100051

Tomoyasu Jo ∗ , Kyoko Yoshihara ∗ , Masaki Ri , Nobuhiro Tsukada , Naoya Mimura , Keiko Fujii , Kentaro Fukushima , Shin-Ichiro Fujiwara , Yuji Shimura , Kyoko Haraguchi , Koji Kato , Atsushi Satake , Akiyo Yoshida , Rikio Suzuki , Junko Ikemoto , Keita Iwaki , Wataru Takeda , Noboru Yonetani , Ryuji Tanosaki , Minami Yamada-Fujiwara , Yasuyuki Arai

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Abstract

Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy has significantly improved management of relapsed or refractory multiple myeloma. However, manufacturing failure due to poor cell growth necessitates revision of treatment strategies that negatively impact patients. To identify risk factors for CAR-T manufacturing failure in patients with myeloma, a nationwide cohort study was performed, analyzing patients who underwent apheresis for idecabtagene vicleucel in Japan. Of 154 patients analyzed, 13 cases (8.4%) experienced manufacturing failure. We compared clinical factors between patients with manufacturing failure (failed group) and those who met specifications (successful group). Patients in the failed group had a higher prevalence of deletion 17p at diagnosis (38.5% vs 14.9%), were more likely to have been treated with alkylating agents within 6 months before apheresis (53.8% vs 23.4%), and had undergone more chemotherapy lines before apheresis (median, 6 vs 5). Additionally, patients with manufacturing failure exhibited significantly lower hemoglobin levels (8.6 vs 10.0 g/dL), platelet counts (5.9 × 10⁴/μL vs 13.8 × 10⁴/μL), and CD4/CD8 ratios (0.169 vs 0.474) than patient with successful manufacturing. Multivariate analysis revealed that low platelet counts (odds ratio [OR], 0.130 for every increase of 10⁵/μL; P = .041), or low CD4/CD8 ratios (OR, 0.100 for each doubling; P = .003) at apheresis increased the risk of manufacturing failure. Alkylating agents within 6 months before apheresis were associated with decreased platelet counts and CD4/CD8 ratios. Manufacturing failure remains an obstacle to CAR-T therapy for patients with myeloma. Avoiding risk factors, such as alkylating agents, and adopting risk-adapted strategies may optimize CAR-T therapy for patients with myeloma.

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低血小板计数和低CD4/CD8比值会增加骨髓瘤中CAR - t细胞制造失败的风险

嵌合抗原受体（CAR） t细胞（CAR- t）疗法显著改善了复发或难治性多发性骨髓瘤的治疗。然而，由于细胞生长不良导致的制造失败需要修改对患者产生负面影响的治疗策略。为了确定骨髓瘤患者CAR-T制造失败的危险因素，进行了一项全国性的队列研究，分析了日本接受了idecabtagene微核单采的患者。在分析的154例患者中，13例（8.4%）出现制造失败。我们比较了制造失败的患者（失败组）和符合规格的患者（成功组）的临床因素。制造失败组患者在诊断时缺失17p的发生率更高（38.5%对14.9%），在采血前6个月内更有可能使用烷基化剂（53.8%对23.4%），并且在采血前接受了更多的化疗（中位数，6对5）。此外，制造失败患者的血红蛋白水平（8.6对10.0 g/dL），血小板计数（5.9 × 104/μL对13.8 × 104/μL），血小板计数（5.9 × 104/μL对13.8 × 104/μL）显着降低。CD4/CD8比值（0.169 vs 0.474）高于制造成功患者。多因素分析显示血小板计数低(比值比[OR]为0.130，每增加105/μL；P = 0.041)，或CD4/CD8比率低(or为0.100，每增加一倍；P = 0.003)的分离增加了制造失败的风险。分离前6个月内使用烷基化剂与血小板计数和CD4/CD8比值降低相关。制造失败仍然是骨髓瘤患者CAR-T治疗的一个障碍。避免风险因素，如烷基化剂，并采用风险适应策略可能优化骨髓瘤患者的CAR-T治疗。

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Blood Neoplasia

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