Zugasti Inés, Tormo-Ratera Marta, Oliver-Caldés Aina, Soler-Perromat Juan Carlos, González-Calle Verónica, Moreno David F, Cabañas Valentín, López-Muñoz Nieves, Bartolomé-Solanas Álvaro, Español-Rego Marta, Reguera-Ortega Juan Luis, Rosiñol Laura, López-Corral Lucía, Tovar Natalia, Rodríguez-Lobato Luis Gerardo, Alvarez Perez Rosa Maria, Varea Sara, Olesti Eulàlia, Gomez-Grande Adolfo, Frutos Laura, Tamayo Pilar, Juan Manel, Moraleda José M, Urbano-Ispizua Álvaro, González-Navarro E Azucena, Martínez-López Joaquín, Mateos Maria-Victoria, Tomás Xavier, Setoain Xavier, Fernández de Larrea Carlos
Hospital Clínic de Barcelona, Institut d'Investigació Biomèdica August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain.
Hospital Universitari Son Espases, Fundació Institut d'Investigació Sanitària Illes Balears, Palma de Mallorca, Mallorca, Spain.
Blood Adv. 2025 Feb 11;9(3):571-582. doi: 10.1182/bloodadvances.2024014360.
Multiple myeloma (MM) remains incurable, with poor outcomes in heavily pretreated patients. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment; however, outcomes after such therapy in patients with soft-tissue plasmacytomas and other bone lesions remain poorly understood. This study included 63 patients with relapsed/refractory MM treated either in the CARTBCMA-HCB-01 clinical trial (ARI0002h; academic B-cell maturation antigen [BCMA]-targeted CAR T-cell therapy) or in compassionate use. The aim was to evaluate the impact of soft-tissue involvement (extramedullary [EMD] and paraskeletal [PS] plasmacytomas) in response, survival and safety. Baseline [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) from 5 participating centers were reviewed centrally. Of 63 patients, 52.4% presented plasmacytomas at the time of inclusion (21 PS, exclusively; and 12 EMD). Per responses, there were no significant differences between patients with and without plasmacytomas. A correlation was present between International Myeloma Working Group responses and those obtained by [18F]FDG-PET/CT at day 100 (Bologna criteria). No differences were observed in progression-free survival (PFS) or overall survival (OS) between patients with or without plasmacytomas. However, both PFS and OS were significantly shorter in patients with EMD. Interestingly, [18F]FDG-PET/CT response assessed on day 100, in accordance with the Bologna criteria, was predictive of survival outcomes. A metabolic tumor volume of ≥25 cm3 at baseline [18F]FDG-PET/CT was associated with earlier disease progression and shorter OS. These results highlight the importance of EMD evaluation by [18F]FDG-PET/CT before and after CAR T-cell infusion. This trial was registered at www.ClinicalTrials.gov as #NCT04309981; and EudraCT, 2019-001472-11.
多发性骨髓瘤（MM）仍然无法治愈，在经过大量预处理的患者中预后较差。嵌合抗原受体（CAR）T细胞疗法已成为一种有前景的治疗方法；然而，软组织浆细胞瘤和其他骨病变患者接受此类治疗后的预后仍知之甚少。本研究纳入了63例复发/难治性MM患者，这些患者在CARTBCMA - HCB - 01临床试验（ARI0002h；学术性B细胞成熟抗原[BCMA]靶向CAR T细胞疗法）或同情用药中接受治疗。目的是评估软组织受累（髓外[EMD]和骨旁[PS]浆细胞瘤）对反应、生存和安全性的影响。对来自5个参与中心的基线[18F]氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）/计算机断层扫描（CT）进行集中审查。63例患者中，52.4%在纳入时存在浆细胞瘤（21例仅为PS，12例为EMD）。就反应而言，有浆细胞瘤和无浆细胞瘤的患者之间无显著差异。国际骨髓瘤工作组的反应与第100天通过[18F]FDG - PET/CT获得的反应之间存在相关性（博洛尼亚标准）。有或无浆细胞瘤的患者在无进展生存期（PFS）或总生存期（OS）方面未观察到差异。然而，EMD患者的PFS和OS均显著缩短。有趣的是，根据博洛尼亚标准在第100天评估的[18F]FDG - PET/CT反应可预测生存结果。基线[18F]FDG - PET/CT时代谢肿瘤体积≥25 cm³与疾病早期进展和较短的OS相关。这些结果突出了在CAR T细胞输注前后通过[18F]FDG - PET/CT评估EMD的重要性。本试验在www.ClinicalTrials.gov上注册为#NCT04309981；在欧盟临床试验注册数据库（EudraCT）中注册为2019 - 001472 - 11。
