Randomized Controlled Trial of Two Different Dosing Regimens of Palifermin to Prevent Mucositis In Multiple Myeloma Patients Receiving One-Day Administration of High-Dose Melphalan
Randomized Controlled Trial of Two Different Dosing Regimens of Palifermin to Prevent Mucositis In Multiple Myeloma Patients Receiving One-Day Administration of High-Dose Melphalan
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Palifermin 的两种不同给药方案预防接受一日大剂量美法仑给药的多发性骨髓瘤患者粘膜炎的随机对照试验
DOI：
10.1182/blood.v116.21.904.904
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发表时间：
2010
期刊：
影响因子：
20.3
通讯作者：
D. Niederwieser
中科院分区：
文献类型：
--
作者：
N. Blijlevens;M. Chateau;G. Kriván;W. Rabitsch;Á. Szomor;R. Pytlík;A. Lissmats;H. Johnsen;T. Ruutu;H. Einsele;D. Niederwieser
摘要904
既往研究表明，在接受自体干细胞移植（ASCT）的患者中，在放化疗预处理前后给予帕利弗明可显著降低重度口腔粘膜炎（OM）的发生率和持续时间。本随机临床试验（RCT）旨在研究在仅化疗预处理环境中以两种不同给药方案给予帕利弗明的疗效和安全性。
在接受ASCT的多发性骨髓瘤（MM）患者中，研究了帕利弗明相对于安慰剂的疗效，帕利弗明在高剂量美法仑（HDM）前/后或仅在HDM前给药。口腔粘膜炎的评估主要基于WHO分级（0/1、2、3或4），安全性主要基于不良事件（AE）报告。
281例患者（平均年龄56 ± 8岁）入组39家临床试验机构; 224例患者随机接受帕利佛明治疗，57例患者随机接受安慰剂治疗。在帕利弗明组中，109例患者随机分配至仅给药前组，在HDM前连续3天接受帕利弗明（60 μg/kg/天）静脉给药，115例受试者随机分配至给药前/给药后组，在HDM前连续3天接受帕利弗明，在ASCT后连续3天再次接受帕利弗明。这两组中实际接受研究药物的受试者数量分别为109例和111例。每天进行OM和安全性评估，直至移植后32天或出院。
安慰剂和帕利弗明在HDM前/后（比值比：0.7 [CI：0.4，1.3]）或HDM前（比值比：1.2 [CI：0.6，2.4]）给药之间OM的最大严重程度无差异。37%（安慰剂组）、38%（HDM前/后）和24%（HDM前）的患者发生重度OM（WHO 3级和4级）。共有275例患者（99.3%）在研究期间发生至少1起AE。HDM前/后组患者的严重AE和研究者报告为治疗相关的AE较多，HDM前组较少，但仍多于安慰剂组。
总体而言，在该临床环境中，安慰剂组与帕利佛明HDM治疗前后组或仅HDM治疗前组之间OM的最大严重程度无统计学显著性差异，化疗预处理方案持续时间短，重度口腔粘膜炎的发生率极低。然而，对于主要和大多数次要疗效终点，仅治疗前组的结果在数值上优于安慰剂组。在HDM前组中接受帕利弗明治疗的患者比HDM前/后组的安全性更好。与先前发表的试验相比，对明显差异的可能解释可能是高剂量化疗的差异和/或本研究中给药前和给药后之间的时间间隔较短。因此，需要进一步探索帕利弗明给药后给药时间相对于给药前以及与明显OM发作和发病机制相关的影响。
披露：Blijlevens：Biovitrum：Consultancy. de Chateau：Biovitrum：就业。Lissmats：Biovitrum：就业。Niederwieser：Biovitrum：Consultancy.
Abstract 904
Palifermin administered pre and post radiochemotherapy conditioning has previously been shown to significantly reduce the incidence and duration of severe oral mucositis (OM) in patients undergoing autologous stem cell transplantation (ASCT). This randomized clinical trial (RCT) aimed to study the efficacy and safety of palifermin when administered in two different dosing regimens in a chemotherapy-only conditioning setting.
The efficacy of palifermin relative to placebo was investigated with palifermin given either pre/post high-dose melphalan (HDM) or pre HDM only in patients with multiple myeloma (MM) undergoing ASCT. Assessment of oral mucositis was primarily based on WHO grades (0/1, 2, 3 or 4) and safety primarily on adverse event (AE) reporting.
281 patients (mean age 56 ± 8 years) were enrolled at 39 centers; 224 patients were randomized to receive palifermin and 57 patients to receive placebo. In the palifermin group, 109 patients were randomized to the pre-only arm, receiving palifermin (60 μg/kg/day) iv for 3 consecutive days before HDM and 115 subjects were randomized to the pre/post arm receiving palifermin on 3 consecutive days before HDM and again on 3 consecutive days after ASCT. The number of subjects actually receiving study drug in the these two arms was 109 and 111, respectively. Assessments of OM and safety were made daily until 32 days post transplant or hospital discharge.
There was no difference in maximum severity of OM between placebo and palifermin administered pre/post HDM (odds ratio: 0.7 [CI: 0.4, 1.3]) or pre HDM (odds ratio: 1.2 [CI: 0.6, 2.4]). Severe OM (WHO grade 3 and 4) occurred in 37% (placebo), 38% (pre/post-HDM) and 24% (pre-HDM) of the patients. A total of 275 patients (99.3%) experienced at least 1 AE during the study. There were more serious AEs and AEs reported as treatment related by the investigators for patients in the pre/post HDM arm, and less in the pre-HDM arm but still more than in the placebo arm.
Overall, no statistically significant differences were observed between placebo and either the palifermin pre-post HDM arm or pre-only HDM arm for maximum severity of OM in this clinical setting with a chemotherapy conditioning regimen of short duration and a comparably low incidence of severe oral mucositis. The pre-only group, however, showed a numerically better result than placebo for the primary and most of the secondary efficacy endpoints. Patients treated with palifermin in the pre HDM arm experienced a more favorable safety profile than the pre/post HDM arm. Possible explanations for the apparent discrepancy compared to previously published trials might be differences in high dose chemotherapy and/or the shorter time interval between the pre and post doses in this study. The impact of the timing of the palifermin post-dose in relation to the pre-dose and in relation to the onset of manifest OM and pathogenesis thus needs to be further explored.
Disclosures: Blijlevens: Biovitrum: Consultancy. de Chateau: Biovitrum : Employment. Lissmats: Biovitrum: Employment. Niederwieser: Biovitrum: Consultancy.