{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:24:12Z","timestamp":1788387852830,"version":"build-2803163510"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"Importance<\/jats:title>Long-term follow-up of patients with multiple myeloma (MM) treated in clinical trials is limited.<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate the cure fraction of newly diagnosed patients with MM treated on early total therapy (TT) protocols.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>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.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Combinational chemotherapy and tandem hematopoietic stem cell transplant with the implementation of immunomodulatory drugs (thalidomide, lenalidomide) and proteosome inhibitor (bortezomib) extended therapy.<\/jats:p><\/jats:sec>Results<\/jats:title>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.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>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.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifiers: NCT00580372<\/jats:ext-link>, NCT00083551<\/jats:ext-link>, NCT00081939<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2025.1394","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T11:30:41Z","timestamp":1749123041000},"page":"910","source":"Crossref","is-referenced-by-count":7,"title":["Long-Term Follow-Up of Patients With Multiple Myeloma Treated on Earlier Total Therapy Protocols"],"prefix":"10.1001","volume":"11","author":[{"given":"Samer","family":"Al Hadidi","sequence":"first","affiliation":[{"name":"Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obada Ehab","family":"Ababneh","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head & 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