Greil Christine, Engelhardt Monika, Finke Jürgen, Wäsch Ralph
University Medical Center Freiburg, Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Cancers (Basel). 2021 Dec 23;14(1):55. doi: 10.3390/cancers14010055.
The development of new inhibitory and immunological agents and combination therapies significantly improved response rates and survival of patients diagnosed with multiple myeloma (MM) in the last decade, but the disease is still considered to be incurable by current standards and the prognosis is dismal especially in high-risk groups and in relapsed and/or refractory patients. Allogeneic hematopoietic stem cell transplantation (allo-SCT) may enable long-term survival and even cure for individual patients via an immune-mediated graft-versus-myeloma (GvM) effect, but remains controversial due to relevant transplant-related risks, particularly immunosuppression and graft-versus-host disease, and a substantial non-relapse mortality. The decreased risk of disease progression may outweigh this treatment-related toxicity for young, fit patients in high-risk constellations with otherwise often poor long-term prognosis. Here, allo-SCT should be considered within clinical trials in first-line as part of a tandem approach to separate myeloablation achieved by high-dose chemotherapy with autologous SCT, and following allo-SCT with a reduced-intensity conditioning to minimize treatment-related organ toxicities but allow GvM effect. Our review aims to better define the role of allo-SCT in myeloma treatment particularly in the context of new immunomodulatory approaches.
在过去十年中,新型抑制性和免疫性药物以及联合疗法的发展显著提高了多发性骨髓瘤(MM)患者的缓解率和生存率,但按照目前的标准,该疾病仍被认为无法治愈,尤其是在高危组以及复发和/或难治性患者中,预后很差。异基因造血干细胞移植(allo-SCT)可能通过免疫介导的移植物抗骨髓瘤(GvM)效应使个别患者获得长期生存甚至治愈,但由于相关的移植相关风险,特别是免疫抑制和移植物抗宿主病以及相当高的非复发死亡率,该方法仍存在争议。对于处于高危状态、长期预后通常较差的年轻健康患者,疾病进展风险的降低可能超过这种与治疗相关的毒性。在此,在一线临床试验中应考虑采用allo-SCT,作为串联方法的一部分,以区分通过高剂量化疗联合自体SCT实现的清髓作用,并在allo-SCT后采用减低强度预处理,以尽量减少与治疗相关的器官毒性,但允许GvM效应。我们的综述旨在更好地界定allo-SCT在骨髓瘤治疗中的作用,特别是在新的免疫调节方法背景下的作用。