PDF(Pubmed)
Abstract：
Most transplant-eligible multiple myeloma (MM) patients undergo autologous peripheral blood stem cell collection (PBSC) using G-CSF with on-demand plerixafor (G ± P). Chemomobilization (CM) can be used as a salvage regimen after G ± P failure or for debulking residual tumor burden ahead of autologous peripheral blood stem cell transplantation (ASCT). Prior studies utilizing cyclophosphamide-based CM have not shown long-term benefits. At our center, intensive CM (ICM) using a PACE- or HyperCVAD-based regimen has been used to mitigate \"excessive\" residual disease based on plasma cell (PC) burden or MM-related biomarkers. Given the lack of efficacy of non-ICM, we sought to determine the impact of ICM on event-free survival (EFS), defined as death, progressive disease, or unplanned treatment escalation. We performed a retrospective study of newly diagnosed MM patients who collected autologous PBSCs with the intent to proceed immediately to ASCT at our center between 7/2020 and 2/2023. Patients were excluded if they underwent a tandem autologous or sequential autologous-allogeneic transplant, had primary PC leukemia, received non-ICM treatment (i.e., cyclophosphamide and/or etoposide), or had previously failed G ± P mobilization. To appropriately evaluate the impact of ICM among those who potentially could have received it, we utilized a propensity score matching (PSM) approach whereby ICM patients were compared to a cohort of non-CM patients matched on pre-ASCT factors most strongly associated with the receipt of ICM. Of 451 patients identified, 61 (13.5%) received ICM (PACE-based, n = 45; hyper-CVAD-based, n = 16). Post-ICM/pre-ASCT, 11 patients (18%) required admission for neutropenic fever and/or infection. Among 51 evaluable patients, the overall response rate was 31%; however, 46 of 55 evaluable patients (84%) saw a reduction in M-spike and/or involved free light chains. Among those evaluated with longitudinal peripheral blood flow cytometry (n = 8), 5 patients (63%) cleared circulating blood PCs post-ICM. Compared to patients mobilized with non-CM, ICM patients collected a slightly greater median number of CD34+ cells (10.8 versus 10.2 × 10⁶/kg, P = .018). The median follow-up was 30.6 months post-ASCT. In a PSM multivariable analysis, ICM was associated with significantly improved EFS (hazard ratio [HR] 0.30, 95% CI 0.14 to 0.67, P = .003), but not improved OS (HR 0.38, 95% CI 0.10 to 1.44, P = .2). ICM was associated with longer post-ASCT inpatient duration (+4.1 days, 95% CI, 2.4 to 5.8, P < .001), more febrile days (+0.96 days, 95% CI 0.50 to 1.4, P < .001), impaired platelet engraftment (HR 0.23, 95% CI 0.06 to 0.87, P = .031), more bacteremia (OR 3.41, 95% CI 1.20 to 9.31, P = .018), and increased antibiotic usage (cefepime: +2.3 doses, 95% CI 0.39 to 4.1, P = .018; vancomycin: +1.0 doses, 95% CI 0.23 to 1.8, P = .012). ICM was independently associated with improved EFS in a matched analysis involving MM patients with excessive disease burden at pre-ASCT workup. This benefit came at the cost of longer inpatient duration, more febrile days, greater incidence of bacteremia, and increased antibiotic usage in the immediate post-ASCT setting. Our findings suggest that ICM could be considered for a subset of MM patients, but its use must be weighed carefully against additional toxicity.
摘要：
背景：大多数符合移植条件的多发性骨髓瘤（MM）患者使用G-CSF和按需plerixafor（G±P）进行自体外周血干细胞收集（PBSC）。化学移植（CM）可用作G±P失败后的抢救方案，或在自体外周血干细胞移植（ASCT）之前减少残留肿瘤负荷。利用基于环磷酰胺的CM的先前研究没有显示出长期益处。
目标：在我们的中心，使用基于PACE或HyperCVAD的方案的强化CM(ICM)已用于减轻基于浆细胞负荷或MM相关生物标志物的“过度残留病”。鉴于非密集CM缺乏疗效，我们试图确定ICM对无事件生存率(EFS)的影响，定义为死亡，进行性疾病,或计划外的治疗升级。
方法：我们对新诊断的MM患者进行了一项回顾性研究，这些患者收集了自体PBSCs，旨在于2020年7月2日至2023年2月在我们的中心立即进行ASCT。如果患者接受串联自体或序贯自体同种异体移植，则被排除在外。患有原发性浆细胞白血病，接受非ICM治疗(即，环磷酰胺和/或依托泊苷)，或以前G±P动员失败。为了适当评估ICM在可能收到ICM的人中的影响，我们采用了倾向评分匹配(PSM)方法,将ICM患者与一组非CM患者进行了比较,这些非CM患者的ASCT前因素与ICM的接收程度密切相关.
结果：在确定的451名患者中，61（13.5％）接受了ICM（基于PACE，n=45；基于超CVAD，n=16)。后ICM/前ASCT，11例患者（18％）因中性粒细胞减少性发热和/或感染而需要入院。在51名可评估的患者中，总反应率为31%；然而，55名可评估患者中的46名(84%)看到M-尖峰减少和/或涉及FLC。在纵向外周血流式细胞术评估的患者中（n=8），5名患者（63％）在ICM后清除了循环血液PC。与非CM动员的患者相比，ICM患者收集的CD34+细胞中位数稍高（10.8vs10.2×10μ/kg，p=.018）。中位随访时间为ASCT后30.6个月。在PSM多变量分析中，ICM与EFS显着改善相关（HR0.30，95％CI0.14至0.67，p=.003），但未改善OS（HR0.38，95%CI0.10至1.44，p=2）。ICM与较长的ASCT住院时间相关(+4.1天,95%CI，2.4至5.8，p<.001)，更多的发热天数(+0.96天，95%CI0.50至1.4，p<.001），血小板植入受损(HR0.23，95%CI0.06至0.87，p=0.031)，更多菌血症（OR3.41，95%CI1.20至9.31，p=0.018），和增加抗生素的使用(头孢吡肟:+2.3剂量，95%CI0.39至4.1，p=0.018；万古霉素：+1.0剂量，95%CI0.23至1.8，p=0.012）。
结论：在ASCT前检查中，在涉及疾病负担过重的MM患者的匹配分析中，ICM与EFS改善独立相关。这种好处是以更长的住院时间为代价的，更多的发热天，菌血症的发生率更高，和增加抗生素的使用后立即ASCT设置。我们的研究结果表明，ICM可以考虑用于部分MM患者，但它的使用必须仔细权衡额外的毒性。
目标：在我们的中心，使用基于PACE或HyperCVAD的方案的强化CM(ICM)已用于减轻基于浆细胞负荷或MM相关生物标志物的“过度残留病”。鉴于非密集CM缺乏疗效，我们试图确定ICM对无事件生存率(EFS)的影响，定义为死亡，进行性疾病,或计划外的治疗升级。
方法：我们对新诊断的MM患者进行了一项回顾性研究，这些患者收集了自体PBSCs，旨在于2020年7月2日至2023年2月在我们的中心立即进行ASCT。如果患者接受串联自体或序贯自体同种异体移植，则被排除在外。患有原发性浆细胞白血病，接受非ICM治疗(即，环磷酰胺和/或依托泊苷)，或以前G±P动员失败。为了适当评估ICM在可能收到ICM的人中的影响，我们采用了倾向评分匹配(PSM)方法,将ICM患者与一组非CM患者进行了比较,这些非CM患者的ASCT前因素与ICM的接收程度密切相关.
结果：在确定的451名患者中，61（13.5％）接受了ICM（基于PACE，n=45；基于超CVAD，n=16)。后ICM/前ASCT，11例患者（18％）因中性粒细胞减少性发热和/或感染而需要入院。在51名可评估的患者中，总反应率为31%；然而，55名可评估患者中的46名(84%)看到M-尖峰减少和/或涉及FLC。在纵向外周血流式细胞术评估的患者中（n=8），5名患者（63％）在ICM后清除了循环血液PC。与非CM动员的患者相比，ICM患者收集的CD34+细胞中位数稍高（10.8vs10.2×10μ/kg，p=.018）。中位随访时间为ASCT后30.6个月。在PSM多变量分析中，ICM与EFS显着改善相关（HR0.30，95％CI0.14至0.67，p=.003），但未改善OS（HR0.38，95%CI0.10至1.44，p=2）。ICM与较长的ASCT住院时间相关(+4.1天,95%CI，2.4至5.8，p<.001)，更多的发热天数(+0.96天，95%CI0.50至1.4，p<.001），血小板植入受损(HR0.23，95%CI0.06至0.87，p=0.031)，更多菌血症（OR3.41，95%CI1.20至9.31，p=0.018），和增加抗生素的使用(头孢吡肟:+2.3剂量，95%CI0.39至4.1，p=0.018；万古霉素：+1.0剂量，95%CI0.23至1.8，p=0.012）。
结论：在ASCT前检查中，在涉及疾病负担过重的MM患者的匹配分析中，ICM与EFS改善独立相关。这种好处是以更长的住院时间为代价的，更多的发热天，菌血症的发生率更高，和增加抗生素的使用后立即ASCT设置。我们的研究结果表明，ICM可以考虑用于部分MM患者，但它的使用必须仔细权衡额外的毒性。
