Al Hadidi Samer, Ababneh Obada Ehab, Schinke Carolina D, Thanendrarajan Sharmilan, Siegel Eric R, Bailey Clyde, Smith Robert, Panozzo Susan B, Zangari Maurizio, Tricot Guido, Shaughnessy John D, Zhan Fenghuang, Sawyer Jeffrey, Barlogie Bart, van Rhee Frits
Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock.
Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston.
JAMA Oncol. 2025 Jun 5. doi: 10.1001/jamaoncol.2025.1394.
Long-term follow-up of patients with multiple myeloma (MM) treated in clinical trials is limited.
To evaluate the cure fraction of newly diagnosed patients with MM treated on early total therapy (TT) protocols.
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. Patients were treated for MM at the University of Arkansas for Medical Sciences. Data cutoff and analysis were July 10, 2023.
Combinational chemotherapy and tandem hematopoietic stem cell transplant with the implementation of immunomodulatory drugs (thalidomide, lenalidomide) and proteosome inhibitor (bortezomib) extended therapy.
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. 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%). Ten-year progression-free survival (PFS) increased from 9% in TT I to 44% in TT IIIA. 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. 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). 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. 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. 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.
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. 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. Future studies are needed to evaluate the long-term benefits of newer generation treatments in MM.
ClinicalTrials.gov Identifiers: NCT00580372, NCT00083551, NCT00081939.
在临床试验中接受治疗的多发性骨髓瘤（MM）患者的长期随访有限。
评估接受早期全疗法（TT）方案治疗的新诊断MM患者的治愈比例。
设计、地点和参与者：纳入了参加TT 1（一项2期单臂临床试验[1989 - 1995]）、TT 2（一项3期随机临床试验[1998 - 2004]）和TT 3A（一项2期单臂临床试验[2004 - 2006]）的新诊断患者。患者在阿肯色大学医学科学部接受MM治疗。数据截止和分析时间为2023年7月10日。
联合化疗、串联造血干细胞移植，并实施免疫调节药物（沙利度胺、来那度胺）和蛋白酶体抑制剂（硼替佐米）延长治疗。
总体而言，1202例新诊断的MM患者参加了3项TT试验，中位（IQR）随访时间为16.6（13.5 - 20.0）年。整个队列的平均（SD）年龄为55.9（9.9）岁，60.6%的患者为男性，1080例为白人（89.9%）。十年无进展生存期（PFS）从TT I中的9%增至TT IIIA中的44%。中位总生存期（OS）随时间改善，接受TT 3A治疗的患者中位OS约为12（95% CI，10.7 - 13.6）年。15年OS从TT 1中的24%、TT 2中的33%和TT 3A中的40%有所改善。接受TT 2方案（随机接受沙利度胺治疗[A组]）治疗的患者20年中位OS为24%（95% CI，19.3% - 30.8%）。对于通过低风险基因表达谱定义的标准风险疾病，结果更好，在TT 2（A组）中20年中位OS为30%（95% CI，23.4% - 38.4%），在TT 3A中15年OS为45%（95% CI，38.2% - 52.1%）。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，这种情况在5至10年时更早出现。与TT 1相比，相对超额风险显示，分别比较TT 2（A组）、TT 2（B组）和TT 3A时，超额死亡率估计降低23%、44%和54%。
在这3项临床试验的二次分析中，接受TT 2方案（A组）治疗的患者中约三分之一以及接受TT 3A方案治疗的患者中约二分之一在初始诊断后20年和15年时仍存活。纳入免疫调节药物和蛋白酶体抑制剂以及串联造血干细胞移植的限时治疗导致OS的累积改善。需要进一步研究来评估新一代MM治疗的长期益处。
ClinicalTrials.gov标识符：NCT00580372、NCT00083551、NCT00081939。
