Diaconescu Daniela, Soare Dan Sebastian, Marinescu Cristina Elena, Ene Georgiana Elena, Bumbea Horia
Bone Marrow Transplantation Unit, Emergency University Hospital, Bucharest, Romania.
Scientific Research Methodology and Hematology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
J Med Life. 2025 Jun;18(6):536-544. doi: 10.25122/jml-2025-0104.
Extramedullary disease (EMD) in multiple myeloma (MM) represents a distinct clinical entity associated with poor prognosis, therapeutic resistance, and aggressive behavior. EMD can occur at diagnosis or during relapses, either contiguous with bone lesions or as soft tissue plasmacytomas due to hematogenous spread. This review outlines the current understanding of EMD pathophysiology, diagnostic challenges, and therapeutic approaches. The review differentiates between bone-related and non-bone-related EMD, highlighting their prognostic implications. Diagnostic strategies rely on advanced imaging modalities, including PET-CT and MRI, and require histopathological confirmation through biopsy and immunohistochemistry. Management includes local therapies, primarily radiotherapy and, in selected cases, surgery, alongside systemic treatments involving proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. New emerging therapies, such as chimeric antigen receptor T cells (CAR-T) and bispecific antibodies, are under evaluation for the treatment of relapsed/refractory EMD. Autologous stem cell transplantation is recommended for eligible patients, with tandem procedures considered in high-risk cases. The role of minimal residual disease (MRD) monitoring is emphasized, employing next-generation sequencing (NGS), flow cytometry, and imaging, with MRD negativity serving as a surrogate marker for treatment efficacy and survival prediction. Despite therapeutic advances, the prognosis for patients with EMD remains unfavorable. The review underscores the necessity of a multidisciplinary approach for accurate diagnosis, individualized treatment, and consistent monitoring. Recognizing EMD as a high-risk MM variant mandates the integration of novel diagnostics and therapies. Future clinical trials must incorporate EMD-specific endpoints to optimize treatment and improve outcomes.
多发性骨髓瘤（MM）中的髓外疾病（EMD）是一种独特的临床实体，与预后不良、治疗抵抗和侵袭性生物学行为相关。EMD可在诊断时或复发期间出现，可与骨病变相邻，也可因血行播散形成软组织浆细胞瘤。本综述概述了目前对EMD病理生理学、诊断挑战和治疗方法的认识。该综述区分了与骨相关和与骨不相关的EMD，强调了它们的预后意义。诊断策略依赖于先进的成像方式，包括PET-CT和MRI，并且需要通过活检和免疫组织化学进行组织病理学确认。治疗包括局部治疗，主要是放疗，在特定情况下还包括手术，同时还有涉及蛋白酶体抑制剂、免疫调节药物和单克隆抗体的全身治疗。新兴疗法，如嵌合抗原受体T细胞（CAR-T）和双特异性抗体，正在评估用于复发/难治性EMD的治疗。建议符合条件的患者进行自体干细胞移植，高危病例考虑采用串联程序。强调了微小残留病（MRD）监测的作用，采用下一代测序（NGS）、流式细胞术和成像技术，MRD阴性作为治疗疗效和生存预测的替代标志物。尽管治疗取得了进展，但EMD患者的预后仍然不佳。该综述强调了多学科方法对于准确诊断、个体化治疗和持续监测的必要性。将EMD识别为高危MM变体要求整合新型诊断和治疗方法。未来的临床试验必须纳入EMD特异性终点，以优化治疗并改善结局。
