Long-Term Follow-Up of Patients With Multiple Myeloma Treated on Earlier Total Therapy Protocols: A Secondary Analysis of 3 Clinical Trials.

Background

To evaluate the cure fraction of newly diagnosed patients with MM treated on early total therapy (TT) protocols.

评估接受早期全面治疗（TT）方案治疗的新诊断MM患者的治愈率。

DESIGN, SETTING, AND PARTICIPANTS: Newly diagnosed patients enrolled in TT 1 (a phase 2 single-arm clinical trial [1989-1995]), TT 2 (a phase 3 randomized clinical trial [1998-2004]) and TT 3A (a phase 2 single-arm clinical trial [2004-2006]) were included.

设计、环境和参与者：纳入了在TT 1（一项II期单臂临床试验[1989-1995]）、TT 2（一项III期随机临床试验[1998-2004]）和TT 3A（一项II期单臂临床试验[2004-2006]）中登记的初诊多发性骨髓瘤患者。

Patients were treated for MM at the University of Arkansas for Medical Sciences.

患者在阿肯色大学医学科学学院接受多发性骨髓瘤治疗。

Data cutoff and analysis were July 10, 2023.

数据截止和分析日期为2023年7月10日。

exposures

Combinational chemotherapy and tandem hematopoietic stem cell transplant with the implementation of immunomodulatory drugs (thalidomide, lenalidomide) and proteosome inhibitor (bortezomib) extended therapy.

联合化疗和串联造血干细胞移植的实施，配合使用免疫调节药物（沙利度胺、雷那度胺）和蛋白酶体抑制剂（硼替佐米）延长了治疗时间。

Results

Overall, 1202 patients with newly diagnosed MM were enrolled in 3 TT trials with a median (IQR) follow-up of 16.6 (13.5-20.0) years.

总体而言，共有1202名新诊断的多发性骨髓瘤患者参与了3项TT试验，中位随访时间为16.6（13.5-20.0）年。

The mean (SD) age of the whole cohort was 55.9 (9.9) years, with 60.6% of patients being male individuals and 1080 being White (89.9%).

整个队列的平均年龄为55.9（9.9）岁，其中60.6%的患者为男性，1080名为白人（89.9%）。

Ten-year progression-free survival(PFS) increased from 9% in TT I to 44% in TT IIIA.

十年无进展生存（PFS）从TT I的9%增加到TT IIIA的44%。

Median overall survival(OS) improved over time, with a median OS of approximately 12 (95% CI, 10.7-13.6) years in patients treated on TT 3A. 15-year OS improved from 24% in TT 1, 33% in TT 2, and 40% in TT 3A.

随着时间的推移，中位总生存（OS）有所改善，在TT 3A治疗的患者中，中位OS约为12年（95%置信区间，10.7-13.6年）。15年总生存率从TT 1的24%提高到TT 2的33%，以及TT 3A的40%。

Median 20-year OS was 24% (95% CI, 19.3%-30.8%) for patients treated on TT 2 protocol who were randomized to receive thalidomide (arm A).

在TT 2方案中接受沙利度胺治疗（A组）的患者，20年总生存率为24%（95%置信区间，19.3%-30.8%）

Outcomes were better for standard risk disease defined by low-risk gene expression profiling with median 20-year OS of 30% (95% CI, 23.4%-38.4%) in TT 2 (arm A) and 15-year OS of 45% (95% CI, 38.2%-52.1%) in TT 3A.

对于低风险基因表达谱定义的标准风险疾病，TT 2（A组）的20年总生存率为30%（95%置信区间，23.4%-38.4%），而TT 3A的15年总生存率为45%（95%置信区间，38.2%-52.1%）

Relative survival rates approached 1 at 10 to 15 years for TT 1, but this occurs earlier, at 5 to 10 years, for TT 2 (arm A), and TT 3A.

TT 1的相对生存率在10至15年时接近1，但对于TT 2（A组）和TT 3A，这一情况发生在5至10年。

Relative excess risk showed an estimated 23%, 44%, and 54% lower excess mortality when comparing TT 2 (arm A), TT 2 (arm B), and TT 3A with TT 1, respectively.

相对超额风险显示，与TT 1相比，TT 2（A组）、TT 2（B组）和TT 3A的超额死亡率分别估计降低了23%、44%和54%。

conclusions_and_relevance

In this secondary analysis of 3 clinical trials, approximately one-third of patients treated on the TT 2 protocol (arm A) and one-half of patients treated on the TT 3A protocol were alive at 20 years and 15 years from initial diagnosis, respectively.

在这三项临床试验的二次分析中，接受TT 2方案（A组）治疗的患者中约有三分之一在初次诊断后20年仍然存活，而接受TT 3A方案治疗的患者中约有一半在初次诊断后15年仍然存活。

Time-limited therapy with the incorporation of immunomodulatory drugs and proteasome inhibitors along with tandem hematopoietic stem cell transplant resulted in cumulative improvement of OS.

结合免疫调节药物和蛋白酶体抑制剂的时间限制性治疗，以及串联造血干细胞移植，导致总生存期的累积改善。

Future studies are needed to evaluate the long-term benefits of newer generation treatments in MM.

需要未来的研究来评估新一代治疗在多发性骨髓瘤中的长期益处。

trial_registration

ClinicalTrials.gov Identifiers: NCT00580372, NCT00083551, NCT00081939.

ClinicalTrials.gov 注册标识：NCT00580372, NCT00083551, NCT00081939。