Barlogie B, Jagannath S, Vesole D H, Naucke S, Cheson B, Mattox S, Bracy D, Salmon S, Jacobson J, Crowley J, Tricot G
Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Blood. 1997 Feb 1;89(3):789-93.
Virtually no progress has been made during more than 2 decades of clinical trials for multiple myeloma (MM) involving standard therapy (ST). Recent studies suggest that dose intensification requiring hematopoietic stem cell support results in higher complete response (CR) rates and extended disease control. "Total Therapy" (TT) consisting of noncross-resistant induction regimens, followed by a double autotransplant (AT) procedure, was administered to 123 untreated patients with symptomatic MM. Upon hematologic recovery, interferon (IFN) maintenance (3 million units [MU]/m2 subcutaneously thrice weekly) was given until disease recurrence/progression. Results were compared with the outcome of untreated patients receiving ST according to Southwest Oncology Group (SWOG) trials. One hundred sixteen pair mates were selected from both TT and among 1,123 patients to match for the major prognostic features. TT induced CR in 40% of all 123 patients (intent-to-treat). By 12 months, 7% had died, including 4% from treatment-related complications. With a median follow-up of 31 months, median durations of event-free survival (EFS) and overall survival (OS) are 49 and 62+ months, respectively. Abnormalities of chromosomes 11q and 13 were associated with inferior outcome, whereas CR within 6 months after induction was a favorable prognostic feature for both EFS and OS. In comparison to ST, TT induced higher PR rates (85% v 52%, P < .0001) (CR rates not available on SWOG trials) and extended EFS (49 v 22 months, P = .0001) and OS (62+ v 48 months, P = .01). Compared to ST, dose intensification with double AT markedly augments tumor cytoreduction, effecting not only higher CR rates but also significantly extending EFS and OS in previously untreated patients with MM.
在超过20年涉及标准疗法（ST）的多发性骨髓瘤（MM）临床试验中，几乎没有取得进展。最近的研究表明，需要造血干细胞支持的剂量强化可导致更高的完全缓解（CR）率和延长疾病控制时间。对123例有症状的未治疗MM患者实施了“全疗法”（TT），该疗法包括非交叉耐药诱导方案，随后进行双自体移植（AT）程序。血液学恢复后，给予干扰素（IFN）维持治疗（300万单位[MU]/m²皮下注射，每周三次），直至疾病复发/进展。将结果与根据西南肿瘤协作组（SWOG）试验接受ST治疗的未治疗患者的结果进行比较。从TT组和1123例患者中选择116对配对对象，以匹配主要预后特征。TT在所有123例患者中诱导40%达到CR（意向性治疗）。到12个月时，7%的患者死亡，其中4%死于与治疗相关的并发症。中位随访31个月，无事件生存期（EFS）和总生存期（OS）的中位持续时间分别为49个月和62 +个月。11号和13号染色体异常与较差的预后相关，而诱导后6个月内达到CR是EFS和OS的有利预后特征。与ST相比，TT诱导更高的部分缓解（PR）率（85%对52%，P <.0001）（SWOG试验中无CR率数据），并延长了EFS（49个月对22个月，P =.0001）和OS（62 +个月对48个月，P =.01）。与ST相比，双AT剂量强化显著增强肿瘤细胞减灭，不仅实现更高的CR率，还显著延长了初治MM患者的EFS和OS。
