Department of Hematology, Oncology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Oncol Res Treat. 2021;44(12):690-699. doi: 10.1159/000520504. Epub 2021 Nov 16.
Multiple myeloma is a so far incurable malignant plasma cell disorder. During the past 2 decades, treatment paradigms substantially changed when novel drugs were introduced initially in treatment of relapsed disease and subsequently also in first-line treatment.
Up to now, first-line treatment differs between patients initially classified as transplant eligible and those who are considered as nontransplant eligible. Transplant-eligible patients receive a primary proteasome inhibitor (PI)-based induction which is being combined with an immunomodulating agent and a CD38-directed monoclonal antibody followed by high-dose melphalan therapy and autologous stem cell transplantation with subsequent maintenance treatment with lenalidomide. Patients who are considered as nontransplant eligible receive upfront treatment preferentially with a continuous combination treatment either with a CD38-directed monoclonal antibody in combination with the immunomodulating agent lenalidomide or a lenalidomide-PI combination followed by lenalidomide maintenance. Key Messages: Primary goal of the initiated treatment is to induce a rapid and deep remission which ideally leads to an eradication of the residual plasma cell clone in sense of a minimal residual disease negativity. Achievement of long-term remission with limited toxicity despite continuous treatment strategies and maintenance or improvement of life-quality is key. Despite successful treatment options, specific difficult-to-treat subgroups, especially patients with high-risk myeloma remain with inferior prognosis and a clear unmet need for novel therapeutic strategies. Future concepts will evaluate cellular treatments and other innovative immunotherapies in first-line treatment in curative intention.
多发性骨髓瘤是一种目前无法治愈的恶性浆细胞疾病。在过去的 20 年中,当新型药物最初用于治疗复发疾病,随后也用于一线治疗时,治疗模式发生了重大变化。
迄今为止,最初被分类为适合移植和不适合移植的患者的一线治疗有所不同。适合移植的患者接受基于主要蛋白酶体抑制剂(PI)的诱导治疗,与免疫调节剂和 CD38 靶向单克隆抗体联合使用,随后进行高剂量美法仑治疗和自体干细胞移植,随后进行来那度胺维持治疗。被认为不适合移植的患者接受一线治疗,优先采用连续联合治疗,要么是 CD38 靶向单克隆抗体与免疫调节剂来那度胺联合使用,要么是来那度胺-PI 联合治疗,然后进行来那度胺维持治疗。
启动治疗的主要目标是诱导快速和深度缓解,理想情况下导致残留浆细胞克隆的根除,达到微小残留病阴性的水平。尽管采用了连续治疗策略和维持或改善生活质量,但实现长期缓解且毒性有限是关键。尽管有了成功的治疗选择,但特定的难治性亚组,尤其是高危骨髓瘤患者,预后仍然较差,迫切需要新的治疗策略。未来的概念将评估细胞治疗和其他创新免疫疗法在治愈意图的一线治疗中的应用。