Approaching the first relapse after autologous transplant in multiple myeloma

Shebli Atrash, Issam Hamadeh, Ashley Matusz-Fisher, Ami Ndiaye, Manisha Bhutani, Peter M. Voorhees, Paul Barry, Saad Z. Usmani
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Abstract

Multiple myeloma(MM) is an incurable plasma cell malignancy. Despite an improvement in OS over the past 2 decades, most patients do experience disease relapse. A subset of patients who experience an early disease relapse within 1-2 years posttransplant, and considered functional high-risk. Recent findings implicated high-risk cytogenetic features and minimal residual disease as negative prognostic factors, each independently associated with early relapse among autologous stem cell transplant recipients(ASCT). The spectrum of disease relapse could range from asymptomatic/biochemical to more aggressive forms such as plasma cell leukemia. Hence, it is imperative that therapy be tailored based on these patterns of relapse upon presentation. The past few years have witnessed an explosion in the armamentarium of second-line agents for the treatment of relapsed MM. Accordingly, choosing the optimal regimen has become quite challenging for the practicing clinician. In this review, we outline the approach for therapy selection, which takes into account underlying comorbid conditions, duration of response, presence of high-risk features, etc Due to a better understanding of disease biology coupled with the advances in molecular techniques, the treatment landscape of relapsed MM (posttransplant) will most likely continue to evolve. Novel agents with distinct modes of action, such as immune therapies and novel oral agents are undergoing investigation in the relapsed setting. Once approved, these agents could potentially alter the course of the disease and possibly challenge the role of ASCT.

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多发性骨髓瘤自体移植术后首次复发的探讨
多发性骨髓瘤(MM)是一种无法治愈的浆细胞恶性肿瘤。尽管在过去20年中OS有所改善,但大多数患者确实经历了疾病复发。移植后1-2年内出现早期疾病复发并被视为功能性高危的患者子集。最近的研究结果表明,高危细胞遗传学特征和最小残留疾病是负面预后因素,每一个因素都与自体干细胞移植受者(ASCT)的早期复发独立相关。疾病复发的范围可能从无症状/生化到更具侵袭性的形式,如浆细胞白血病。因此,必须根据这些复发模式进行治疗。在过去的几年里,用于治疗复发性MM的二线药物的数量激增。因此,选择最佳方案对执业临床医生来说变得非常具有挑战性。在这篇综述中,我们概述了治疗选择的方法,其中考虑了潜在的共病条件、反应持续时间、高风险特征的存在等。由于对疾病生物学的更好理解以及分子技术的进步,复发性MM(移植后)的治疗前景很可能会继续发展。具有不同作用模式的新型药物,如免疫疗法和新型口服药物,正在复发环境中进行研究。一旦获得批准,这些药物可能会改变疾病的进程,并可能挑战ASCT的作用。
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