Tabayashi Takayuki
Department of Hematology, Saitama Medical Center, Saitama Medical University.
Rinsho Ketsueki. 2019;60(9):1257-1264. doi: 10.11406/rinketsu.60.1257.
The introduction of proteasome inhibitors (PIs), such as bortezomib (BTZ), and immunomodulatory drugs (IMiDs), including thalidomide (THAL) and lenalidomide (LEN), as first-line therapies in multiple myeloma (MM) has markedly improved the clinical outcomes of patients. However, MM remains incurable, and most patients eventually relapse. Moreover, prognosis is poor in patients who exhibit resistance to BTZ or LEN, and novel therapeutic approaches for such patients are urgently needed. Currently, the following six drugs are available for use in relapsed patients: second generation PIs (carfilzomib and ixazomib), an IMiD (pomalidomide), a histone deacetylase (HDAC) inhibitor (panobinostat), and two monoclonal antibodies (elotuzumab and daratumumab). The choice of treatment should be individualized based on certain factors, such as age, presence of comorbidities, frailty, cytogenetic risk, efficacy and toxicity of prior treatments, and the duration of the previous response. A course of triplet therapy containing two novel agents along with DEX is recommended, on first relapse, in fit and healthy patients, whereas doublet therapy is preferred for unfit or frail patients. Retreatment of relapsed/refractory MM (RRMM) with monoclonal antibodies and IMiDs is promising because these drugs have immunostimulatory effects. In addition, novel agents, including an anti-BCMA antibody-drug conjugate, are being studied. Clinical trials are needed to define the optimal treatment strategy for RRMM.
蛋白酶体抑制剂(PIs)如硼替佐米(BTZ)以及免疫调节药物(IMiDs)包括沙利度胺(THAL)和来那度胺(LEN)作为多发性骨髓瘤(MM)的一线治疗药物的引入,显著改善了患者的临床结局。然而,MM仍然无法治愈,大多数患者最终会复发。此外,对BTZ或LEN耐药的患者预后较差,迫切需要针对这类患者的新型治疗方法。目前,有以下六种药物可用于复发患者:第二代PIs(卡非佐米和伊沙佐米)、一种IMiD(泊马度胺)、一种组蛋白去乙酰化酶(HDAC)抑制剂(帕比司他)以及两种单克隆抗体(埃罗妥珠单抗和达雷妥尤单抗)。治疗方案的选择应根据某些因素个体化制定,如年龄、合并症的存在、身体虚弱程度、细胞遗传学风险、既往治疗的疗效和毒性以及先前缓解的持续时间。对于首次复发的健康适宜患者,推荐采用包含两种新型药物以及地塞米松(DEX)的三联疗法,而对于身体不适或虚弱的患者,双联疗法更为合适。用单克隆抗体和IMiDs对复发/难治性MM(RRMM)进行再治疗具有前景,因为这些药物具有免疫刺激作用。此外,包括抗BCMA抗体药物偶联物在内的新型药物正在研究中。需要进行临床试验以确定RRMM的最佳治疗策略。