Nozzoli Chiara, Pucillo Martina, Giaccone Luisa, Rambaldi Alessandro, Stanghellini Maria Teresa Lupo, Benedetti Edoardo, Russo Domenico, Mordini Nicola, Mangiacavalli Silvia, Bernasconi Paolo, Parma Matteo, Carluccio Paola, Galieni Piero, Rivela Paolo, Martino Massimo, Chiusolo Patrizia, Isola Miriam, De Martino Maria, Oldani Elena, Degrandi Eliana, Boncompagni Riccardo, Antonioli Elisabetta, Carnevale Fabrizio, Tozzi Monica, Selleri Carmine, Fanin Renato, Patriarca Francesca
Cell Therapy and Transfusion Medicine Unit, Careggi University Hospital, Florence, Italy.
Azienda Sanitaria Universitaria Friuli Centrale, DMED, University of Udine, Udine, Italy.
Transplant Cell Ther. 2025 Jan;31(1):26.e1-26.e13. doi: 10.1016/j.jtct.2024.10.015. Epub 2024 Nov 4.
Although allogeneic stem cell transplantation (allo-SCT) is curative for only a minority of patients with multiple myeloma (MM), patients who relapse after allo-SCT can experience long-term survival, suggesting a synergy between antimyeloma drugs administered after allo-SCT and donor T cells. We retrospectively evaluated the outcome of MM patients reported to the Gruppo Italiano Trapianto Midollo Osseo e Terapia Cellulare (GITMO) network who underwent allo-SCT between 2009 and 2018, to identify predictors of long-term outcome in the whole population (242 patients) and predictors of prolonged overall survival (OS) after relapse in the subgroup of relapsed patients (118 patients). In the whole population, at a median follow-up of 40.9 months after allo-SCT, the median duration of OS and progression-free survival (PFS) were 39.4 and 19.0 months after allo-SCT, respectively. The cumulative incidence of nonrelapse mortality (NRM) was 10.3% at 1 year and 27.6% at 5 years. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 19.8%, and the 5-year cumulative incidence of moderate or severe chronic GVHD was 31.8%. In the multivariate model, older age at transplantation (P = .020), receipt of >2 lines of therapy before allo-SCT (P = .003), and transplantation from an unrelated or haploidentical donor (P = .025) were significant factors associated with reduced OS. Relapse after allo-SCT occurred in 118 patients (59%) at a median of 14.3 months (interquartile range, 7.2 to 26.9 months). Twenty patients (17%) received only steroids, radiotherapy, or supportive care; 41 (35%) received 1 line of salvage treatment; 23 (19%) received 2 lines of salvage treatment; and 34 (29%) received 3 or 4 lines of salvage treatment. Nine patients were treated exclusively with chemotherapy, 9 received at least 1 salvage treatment including immunomodulating agents, 43 patients were treated with at least 1 rescue therapy including proteasome inhibitors, and 37 patients received at least 1 salvage treatment including monoclonal antibodies (33 with daratumumab, 1 with elotuzumab, 1 with isatuximab, and 2 with belantamab). The median OS of relapsed patients was 38.5 months from allo-SCT and 20.2 months from relapse. In multivariate analysis, OS after relapse was significantly prolonged in patients with a longer time to relapse after allo-SCT (time to relapse 6 to 24 months, P = .016; time to relapse ≥24 months, P < .001) and in those who had received at least 3 lines of salvage treatment (P < .036) and donor lymphocyte infusion (DLI) (P = .020). In this study, patients who underwent transplantation in early phases of disease and with an HLA-identical sibling donor had the best chance of long-term survival. Late relapse after allo-SCT, multiple courses of salvage treatment, and an association with DLI could allow for long-term disease control in patients who experienced relapse after allo-SCT.
尽管异基因干细胞移植（allo-SCT）仅能治愈少数多发性骨髓瘤（MM）患者，但allo-SCT后复发的患者仍可实现长期生存，这表明allo-SCT后给予的抗骨髓瘤药物与供体T细胞之间存在协同作用。我们回顾性评估了2009年至2018年间向意大利骨髓移植和细胞治疗组（GITMO）网络报告的接受allo-SCT的MM患者的结局，以确定整个人群（242例患者）长期结局的预测因素以及复发患者亚组（118例患者）复发后总生存期（OS）延长的预测因素。在整个人群中，allo-SCT后中位随访40.9个月，allo-SCT后OS和无进展生存期（PFS）的中位持续时间分别为39.4个月和19.0个月。1年时非复发死亡率（NRM）的累积发生率为10.3%，5年时为27.6%。II-IV级急性移植物抗宿主病（GVHD）的累积发生率为19.8%，中度或重度慢性GVHD的5年累积发生率为31.8%。在多变量模型中，移植时年龄较大（P = .020）、allo-SCT前接受>2线治疗（P = .003）以及来自无关或单倍体供体的移植（P = .025）是与OS降低相关的显著因素。118例患者（59%）在allo-SCT后复发，中位复发时间为14.3个月（四分位间距，7.2至26.9个月）。20例患者（17%）仅接受了类固醇、放疗或支持治疗；41例（35%）接受了1线挽救治疗；23例（19%）接受了2线挽救治疗；34例（29%）接受了3或4线挽救治疗。9例患者仅接受化疗，9例接受了至少1次包括免疫调节剂在内的挽救治疗，43例患者接受了至少1次包括蛋白酶体抑制剂在内的挽救治疗，37例患者接受了至少1次包括单克隆抗体在内的挽救治疗（33例使用达雷妥尤单抗，1例使用埃罗妥珠单抗，1例使用isatuximab，2例使用贝利司他单抗）。复发患者的OS从allo-SCT起为38.5个月，从复发起为20.2个月。在多变量分析中，allo-SCT后复发时间较长的患者（复发时间6至24个月，P = .016；复发时间≥24个月，P < .001）、接受了至少3线挽救治疗的患者（P < .036）以及接受了供体淋巴细胞输注（DLI）的患者（P = .020）复发后的OS显著延长。在本研究中，在疾病早期接受移植且有HLA相同同胞供体的患者长期生存机会最佳。allo-SCT后的晚期复发、多疗程挽救治疗以及与DLI的联合应用可使allo-SCT后复发的患者实现长期疾病控制。
