Bolli Niccolo', Sgherza Nicola, Curci Paola, Rizzi Rita, Strafella Vanda, Delia Mario, Gagliardi Vito Pier, Neri Antonino, Baldini Luca, Albano Francesco, Musto Pellegrino
Division of Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy.
Department of Oncology and Onco-Hematology, University of Milan, 20122 Milan, Italy.
J Clin Med. 2021 Jan 22;10(3):421. doi: 10.3390/jcm10030421.
Smoldering multiple myeloma (SMM), an asymptomatic plasma cell neoplasm, is currently diagnosed according to the updated IMWG criteria, which reflect an intermediate tumor mass between monoclonal gammopathy of undetermined significance (MGUS) and active MM. However, SMM is a heterogeneous entity and individual case may go from an "MGUS-like" behavior to "early MM" with rapid transformation into symptomatic disease. This wide range of clinical outcomes poses challenges for prognostication and management of individual patients. However, initial studies showed a benefit in terms of progression or even survival for early treatment of high-risk SMM patients. While outside of clinical trials the conventional approach to SMM generally remains that of close observation, these studies raised the question of whether early treatment should be offered in high-risk patients, prompting evaluation of several different therapeutic approaches with different goals. While delay of progression to MM with a non-toxic treatment is clearly achievable by early treatment, a convincing survival benefit still needs to be proven by independent studies. Furthermore, if SMM is to be considered less biologically complex than MM, early treatment may offer the chance of cure that is currently not within reach of any active MM treatment. In this paper, we present updated results of completed or ongoing clinical trials in SMM treatment, highlighting areas of uncertainty and critical issues that will need to be addressed in the near future before the "watch and wait" paradigm in SMM is abandoned in favor of early treatment.
冒烟型多发性骨髓瘤（SMM）是一种无症状的浆细胞肿瘤，目前根据国际骨髓瘤工作组（IMWG）的更新标准进行诊断，该标准反映了意义未明的单克隆丙种球蛋白病（MGUS）和活动性MM之间的中间肿瘤负荷。然而，SMM是一种异质性疾病，个别病例可能从“MGUS样”行为转变为“早期MM”，并迅速转化为有症状的疾病。这种广泛的临床结局给个体患者的预后评估和管理带来了挑战。然而，初步研究表明，早期治疗高危SMM患者在疾病进展甚至生存方面具有益处。虽然在临床试验之外，SMM的传统治疗方法通常仍是密切观察，但这些研究提出了一个问题，即高危患者是否应接受早期治疗，这促使人们评估了几种具有不同目标的不同治疗方法。虽然通过早期治疗显然可以通过无毒治疗延迟进展为MM，但独立研究仍需证明其令人信服的生存益处。此外，如果认为SMM的生物学复杂性低于MM，那么早期治疗可能提供治愈的机会，而这是目前任何活动性MM治疗都无法实现的。在本文中，我们展示了SMM治疗中已完成或正在进行的临床试验的最新结果，强调了不确定性领域以及在SMM的“观察等待”模式被放弃而转向早期治疗之前不久需要解决的关键问题。
