Department of Medicine, Imperial College London, UK
Department of Biology, Tor Vergata University of Rome, Italy.
Haematologica. 2018 Mar;103(3):514-521. doi: 10.3324/haematol.2017.181339. Epub 2017 Dec 7.
Melphalan at a dose of 200 mg/m is standard conditioning prior to autologous hematopoietic stem cell transplantation for multiple myeloma, but a dose of 140 mg/m is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine whether melphalan 200 mg/m and melphalan 140 mg/m are equally effective and tolerable in clinically relevant patient subgroups we analyzed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, hematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 mg/m (n=245) and melphalan 200 mg/m (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 mg/m in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 mg/m melphalan 140 mg/m: 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favored melphalan 140 mg/m for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 mg/m and melphalan 140 mg/m patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favor the use of melphalan 200 mg/m or melphalan 140 mg/m for key transplant outcomes (NCT01362972).
美法仑 200mg/m2 是多发性骨髓瘤自体造血干细胞移植前的标准预处理方案，但在临床上，对于那些被认为有过度毒性风险的患者，通常使用 140mg/m2 的剂量。为了确定美法仑 200mg/m2 和 140mg/m2 在临床相关患者亚组中的疗效和耐受性是否相当，我们使用一系列 Cox 比例风险模型分析了 1964 例首次单倍体自体移植病例。总体生存、无进展生存、复发累积发生率、非复发死亡率、造血恢复和第二原发恶性肿瘤发生率在美法仑 140mg/m2 组（n=245）和 200mg/m2 组（n=1719）之间无显著差异。多变量亚组分析显示，移植时的疾病状态与总体生存、无进展生存和复发累积发生率相互作用，与美法仑 200mg/m2 相比，部分缓解以下的患者具有显著优势（美法仑 200mg/m2 与美法仑 140mg/m2 的调整风险比：0.5、0.54 和 0.56）。相比之下，非常好的部分缓解或完全缓解显著有利于美法仑 140mg/m2 组的总体生存（调整后的风险比：2.02）。年龄、肾功能、先前的蛋白酶体抑制剂治疗、性别或 Karnofsky 评分在美法仑剂量组中与总体/无进展生存或复发率无相互作用。在具有高危或标准风险染色体异常的患者中，美法仑 200mg/m2 与美法仑 140mg/m2 之间的生存或复发率无显著差异。总之，移植时的缓解状态可能有利于使用美法仑 200mg/m2 或美法仑 140mg/m2 来获得关键的移植结果（NCT01362972）。
