Lendvai N, Cohen A D, Cho H J
1] Myeloma Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA [2] Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA.
Division of Hematology/Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
Bone Marrow Transplant. 2015 Jun;50(6):770-80. doi: 10.1038/bmt.2015.5. Epub 2015 Mar 9.
Autologous hematopoietic cell transplantation (auto-HCT) is the standard consolidation therapy for plasma cell myeloma patients following induction therapy. Auto-HCT improves disease-free survival (DFS), but is generally not curative. The allogeneic HCT experience demonstrated that T-cell immunotherapy can confer long-term DFS. Preclinical and clinical data indicate that myeloma-associated Ags elicit humoral and cellular immune responses (IRs) in myeloma patients. These findings strongly suggest that the immunotherapeutic strategies, including immune checkpoint inhibitors, therapeutic cancer vaccines and adoptive cellular therapies, are promising avenues of clinical research that may be most applicable in the minimal residual disease state following auto-HCT. These strategies are designed to prime or augment antimyeloma IRs and promote a 'host-vs-myeloma' effect that may result in durable DFS. Innovative clinical trials investigating immune checkpoint inhibitors and cancer vaccines have demonstrated that robust immunity against myeloma-associated Ags can be elicited in the setting of auto-HCT. A diverse array of immunotherapeutic strategies have entered clinical trials in myeloma, including PD-1/PD-L1 inhibitors, DC/myeloma cell fusion vaccines and adoptive chimeric Ag receptor T-cell therapy, and further investigation of combinations of immunologic and pharmaceutical agents are expected in the near future. In this review, we will discuss the preclinical data supporting immunotherapy in auto-HCT for myeloma, clinical investigation of these strategies and the future prospects of immunotherapy in pursuit of the goal of curative therapy.
自体造血细胞移植(auto-HCT)是浆细胞骨髓瘤患者诱导治疗后的标准巩固治疗方法。自体造血细胞移植可改善无病生存期(DFS),但通常无法治愈。异基因造血细胞移植的经验表明,T细胞免疫疗法可带来长期无病生存期。临床前和临床数据表明,骨髓瘤相关抗原可在骨髓瘤患者中引发体液免疫和细胞免疫反应(IRs)。这些发现强烈表明,包括免疫检查点抑制剂、治疗性癌症疫苗和过继性细胞疗法在内的免疫治疗策略是很有前景的临床研究途径,可能最适用于自体造血细胞移植后的微小残留病状态。这些策略旨在启动或增强抗骨髓瘤免疫反应,并促进“宿主对抗骨髓瘤”效应,这可能会带来持久的无病生存期。研究免疫检查点抑制剂和癌症疫苗的创新性临床试验表明,在自体造血细胞移植的背景下,可以引发针对骨髓瘤相关抗原的强大免疫反应。一系列不同的免疫治疗策略已进入骨髓瘤的临床试验,包括PD-1/PD-L1抑制剂、树突状细胞/骨髓瘤细胞融合疫苗和过继性嵌合抗原受体T细胞疗法,预计在不久的将来会进一步研究免疫制剂和药物制剂的联合使用。在这篇综述中,我们将讨论支持骨髓瘤自体造血细胞移植免疫治疗的临床前数据、这些策略的临床研究以及免疫治疗在追求治愈性治疗目标方面的未来前景。