Mina Roberto, Petrucci Maria Teresa, Corradini Paolo, Spada Stefano, Patriarca Francesca, Cerrato Chiara, De Paoli Lorenzo, Pescosta Norbert, Ria Roberto, Malfitano Alessandra, Musto Pellegrino, Baldini Luca, Guglielmelli Tommasina, Gamberi Barbara, Mannina Donato, Benevolo Giulia, Zambello Renato, Falcone Antonietta Pia, Palumbo Antonio, Nagler Arnon, Calafiore Valeria, Hájek Roman, Spencer Andrew, Boccadoro Mario, Bringhen Sara
Myeloma Unit, Division of Hematology, University of Torino, Azienda-Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
Hematology, Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy.
Clin Lymphoma Myeloma Leuk. 2018 Aug;18(8):533-540. doi: 10.1016/j.clml.2018.05.019. Epub 2018 May 28.
High-dose therapy with autologous stem cell transplantation (HDT-ASCT) and maintenance treatment with novel agents are the best options for patients with newly diagnosed multiple myeloma, increasing the rate of complete response (CR) and prolonging progression-free survival (PFS) and overall survival (OS). Indeed, the achievement of a CR is a predictor of long-term survival among transplant-eligible patients. However, it is unclear whether patients reaching a CR after induction treatment could receive less intense consolidation or avoid maintenance therapy.
We analyzed CR patients treated in 2 phase III trials, GIMEMA-RV-MM-PI-209 and RV-MM-EMN-441, to compare HDT-ASCT with an R-Alk (lenalidomide, alkylator) regimen as consolidation, and lenalidomide (R) maintenance with no maintenance. The primary endpoints were PFS, second PFS (PFS2), and OS from consolidation and maintenance (_m).
Overall, the data from 166 patients in CR were analyzed, 95 in the HDT-ASCT group and 71 in the R-Alk group. The CR patients who received HDT-ASCT had a better PFS (hazard ratio [HR], 0.55; P = .01), PFS2 (HR, 0.46; P = .02), and OS (HR, 0.42; P = .03) compared with patients randomized to R-Alk. The survival benefit with HDT-ASCT was confirmed among all the subgroups, according to age, International Staging System (ISS stage, cytogenetic profile, and receipt of maintenance therapy. CR patients who received lenalidomide maintenance had a better PFS_m (4 years: 54% vs. 19%; HR, 0.43; P = .02) compared with those who received no maintenance. However, no difference was observed in terms of PFS2_m (4 years: 72% vs. 58%; HR, 0.83; P = .67) and OS_m (4 years: 79% vs. 72%; HR, 0.82; P = .73) with maintenance therapy.
Even in CR patients, outcomes were improved by an intensified approach with HDT-ASCT consolidation and lenalidomide-based maintenance therapy.
高剂量疗法联合自体干细胞移植（HDT-ASCT）以及使用新型药物进行维持治疗是新诊断的多发性骨髓瘤患者的最佳选择，可提高完全缓解（CR）率，延长无进展生存期（PFS）和总生存期（OS）。确实，达到CR是适合移植患者长期生存的一个预测指标。然而，诱导治疗后达到CR的患者是否可以接受强度较低的巩固治疗或避免维持治疗尚不清楚。
我们分析了在两项III期试验GIMEMA-RV-MM-PI-209和RV-MM-EMN-441中接受治疗的CR患者，以比较HDT-ASCT与R-Alk（来那度胺、烷化剂）方案作为巩固治疗，以及来那度胺（R）维持治疗与不进行维持治疗的效果。主要终点是巩固和维持治疗后的PFS、第二次PFS（PFS2）和OS（_m）。
总体而言，分析了166例CR患者的数据，HDT-ASCT组95例，R-Alk组71例。与随机分配接受R-Alk治疗的患者相比，接受HDT-ASCT的CR患者具有更好的PFS（风险比[HR]，0.55；P = .01）、PFS2（HR，0.46；P = .02）和OS（HR，0.42；P = .03）。根据年龄、国际分期系统（ISS分期）、细胞遗传学特征和维持治疗情况，在所有亚组中均证实了HDT-ASCT的生存获益。接受来那度胺维持治疗的CR患者与未接受维持治疗的患者相比，PFS_m更好（4年：54%对19%；HR，0.43；P = .02）。然而，在PFS2_m（4年：72%对58%；HR，0.83；P = .67）和OS_m（4年：79%对72%；HR，0.82；P = .73）方面，维持治疗未观察到差异。
即使在CR患者中，采用HDT-ASCT巩固和来那度胺维持治疗的强化方法也能改善预后。
