Straka Christian, Liebisch Peter, Salwender Hans, Hennemann Burkhard, Metzner Bernd, Knop Stefan, Adler-Reichel Sigrid, Gerecke Christian, Wandt Hannes, Bentz Martin, Bruemmendorf Tim Hendrik, Hentrich Marcus, Pfreundschuh Michael, Wolf Hans-Heinrich, Sezer Orhan, Bargou Ralf, Jung Wolfram, Trümper Lorenz, Hertenstein Bernd, Heidemann Else, Bernhard Helga, Lang Nicola, Frickhofen Norbert, Hebart Holger, Schmidmaier Ralf, Sandermann Andreas, Dechow Tobias, Reichle Albrecht, Schnabel Brigitte, Schäfer-Eckart Kerstin, Langer Christian, Gramatzki Martin, Hinke Axel, Emmerich Bertold, Einsele Hermann
Schön Klinik Starnberger See, Berg, Germany
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München (LMU), Germany.
Haematologica. 2016 Nov;101(11):1398-1406. doi: 10.3324/haematol.2016.151860. Epub 2016 Aug 4.
Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction. For all patients, double autologous transplantation after melphalan 140 mg/m (MEL140) was planned. The primary end point was progression-free survival. Of 420 eligible patients, 85% received a first transplant and 69% completed double transplantation. Treatment duration was short with a median of 7.7 months with induction chemotherapy cycles and 4.6 months without induction. On an intention-to-treat basis, median progression-free survival with induction chemotherapy cycles (207 patients) was 21.4 months versus 20.0 months with no induction cycles (213 patients) (hazard ratio 1.04, 95% confidence interval 0.84-1.28; P=0.36). Per protocol, progression-free survival was 23.7 months versus 23.0 months (P=0.28). Patients aged 65 years or over (55%) did not have an inferior outcome. Patients with low-risk cytogenetics [absence of del17p13, t(4;14) and 1q21 gains] showed a favorable overall survival and included the patients with sustained first remission. MEL140 was associated with a low rate of severe mucositis (10%) and treatment-related deaths (1%). Based on hazard ratio, the short treatment arm consisting of mobilization chemotherapy and tandem MEL140 achieved 96% of the progression-free survival, demonstrating its value as an independent component of therapy in older patients with multiple myeloma who are considered fit for autologous transplantation. (clinicaltrials.gov identifier: 02288741).
自体移植对于老年多发性骨髓瘤患者存在争议。年龄调整后的大剂量美法仑的作用以及诱导化疗周期的影响仍不明确。共有434例60至70岁的患者被随机分配接受4个周期的基于蒽环类药物的标准诱导化疗或不接受诱导化疗。对于所有患者，计划在给予140mg/m²美法仑（MEL140）后进行两次自体移植。主要终点是无进展生存期。在420例符合条件的患者中，85%接受了首次移植，69%完成了两次移植。诱导化疗周期组的治疗持续时间较短，中位时间为7.7个月，未接受诱导化疗组为4.6个月。在意向性治疗分析中，接受诱导化疗周期的患者（207例）中位无进展生存期为21.4个月，未接受诱导化疗周期的患者（213例）为20.0个月（风险比1.04，95%置信区间0.84 - 1.28；P = 0.36）。根据方案分析，无进展生存期分别为23.7个月和23.0个月（P = 0.28）。65岁及以上的患者（55%）预后并不差。具有低风险细胞遗传学特征（不存在del17p13、t(4;14)和1q21扩增）的患者总生存期良好，包括持续首次缓解的患者。MEL140与严重黏膜炎发生率低（10%）和治疗相关死亡率低（1%）相关。基于风险比，由动员化疗和串联MEL140组成的短疗程治疗组实现了96%的无进展生存期，证明了其作为适合自体移植的老年多发性骨髓瘤患者独立治疗组成部分的价值。（临床试验注册号：02288741）
