背景:霉酚酸酯(MMF)通常包括在单倍体(haplo)造血细胞移植(HCT)后的基于移植后环磷酰胺(PTCy)的移植物抗宿主病(GVHD)预防中。在非PTCy设置中,已证明,较高的MMF剂量/kg可降低急性移植物抗宿主病(GVHD)的发生率.当与PTCy结合使用时,MMF以15mg/kg每日三次给药,直至最大剂量为3g/天。因此,体重≥67kg的患者接受3g/天和可变剂量/kg的MMF.
目的:我们研究了MMF剂量/kg对单倍体PBSCT和基于PTCy的GVHD预防后临床结局的影响。
方法:纳入2014年4月至2020年8月在莫维特癌症中心或希望市接受单倍体T细胞充足外周血干细胞移植(PBSCT)和PTCy/MMF以及他克莫司或西罗莫司的所有连续成人血液系统恶性肿瘤患者。对于分析,MMF剂量相对于患者实际体重(mg/kg/天),分层为低(<29mg/kg/天),低中间(29-34毫克/千克/天),高中间体(35-41毫克/千克/天),和高(>41毫克/千克/天)。
结果:纳入了三百八十六名患者。其中,54例患者接受低剂量,73低中间,137高中间和122高剂量MMF按相对重量暴露。在多变量分析中,与高剂量组相比,低MMF剂量暴露与复发率降低相关(HR=0.45,95%CI:0.21~0.94,p=0.03).与高MMF剂量暴露相比,低的患者的PFS更高(HR=0.58,95%CI:0.34至0.99,p=0.045)。MMF相对剂量暴露与植入无关,GVHD,非复发死亡率,或操作系统。
结论:在这项研究中,患者接受单倍体PBSCT与PTCy为基础的GVHD预防,低MMF剂量/kg与复发率和PFS改善相关.未来的前瞻性研究应研究使用PTCy方案时MMF的最佳给药策略。
BACKGROUND: Mycophenolate mofetil (MMF) is commonly included in post-transplant cyclophosphamide (PTCy) based graft-versus-host disease (GVHD) prophylaxis after haploidentical (haplo) hematopoietic cell transplant (HCT). In the non-PTCy setting, higher MMF dose/kg has been shown to reduce rates of acute graft-versus-host disease (GVHD). When used in conjunction with PTCy, MMF is dosed at 15 mg/kg three times daily up to a maximum dose of 3 g/day. Thus, patients who weigh ≥67 kg receive 3 g/day and a variable dose/kg of MMF.
OBJECTIVE: We investigated the impact of MMF dose/kg on clinical outcomes following haploidentical PBSCT with PTCy-based GVHD prophylaxis.
METHODS: All consecutive adult patients with hematologic malignancies receiving haploidentical T cell replete peripheral blood stem cell transplant (PBSCT) with PTCy/MMF and either tacrolimus or sirolimus at the Moffitt Cancer Center or City of Hope between April 2014-August 2020 were included. For analyses, MMF dose relative to patient actual body weight (mg/kg/day), was stratified into categories of low (<29 mg/kg/day), low intermediate (29-34 mg/kg/day), high intermediate (35-41 mg/kg/day), and high (>41 mg/kg/day).
RESULTS: Three hundred eighty-six patients were included. Of these, 54 patients received low dose, 73 low intermediate, 137 high intermediate and 122 high dose MMF by relative weight exposure. In multivariate analysis, low MMF dose exposure was associated with reduced rates of relapse in comparison to the high dose group (HR=0.45, 95% CI: 0.21 to 0.94, p=0.03). This led to superior PFS among patients with low compared to high MMF dose exposure (HR=0.58, 95% CI: 0.34 to 0.99, p=0.045). MMF relative dose exposure was not associated with engraftment, GVHD, non-relapse mortality, or OS.
CONCLUSIONS: In this study of patients receiving haploidentical PBSCT with PTCy based GVHD prophylaxis, low MMF dose/kg was associated with improved rates of relapse and PFS. Future prospective studies should investigate optimal dosing strategies of MMF when given with the PTCy regimen.