{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:33:48Z","timestamp":1789205628112,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The use of 4-drug induction regimens for treatment na\u00efve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment na\u00efve NDMM patients to either a 4-drug or 3-drug induction regimen. We included 11 trials which represented 6509 unique patients. PFS for all trials in the meta-analysis was 54 months with a 4-drug induction and 8.9 months with a 3-drug induction (HR: 0.49; 95% CI: 0.45; 0.54), but there was no benefit to using a 4-drug induction that did not include an anti-CD38 antibody (PFS 4-drug 8.1 months, PFS 3-drug 8.0 months; HR 0.95; 95% CI 0.86; 1.06). Adverse events were more frequent with the quadruplet regimens but were predominately mild. High-grade (\u22653) adverse events (AEs) that were more common with 4-drug regimens were infections (RR: 1.34; 95% CI 1.17; 1.54) and thrombocytopenia (RR: 1.39; 95% CI 1.12; 1.74). This study suggests that 4-drug induction regimens which include an anti-CD38 antibody improve efficacy although with additional toxicity in NDMM patients.<\/jats:p>","DOI":"10.3390\/cancers16172938","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T12:53:19Z","timestamp":1724417599000},"page":"2938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Comparative Meta-Analysis of Triplet vs. Quadruplet Induction Regimens in Newly Diagnosed, Treatment Na\u00efve, Multiple Myeloma"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2702-8225","authenticated-orcid":false,"given":"Barry","family":"Paul","sequence":"first","affiliation":[{"name":"US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS 66205, USA"},{"name":"Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health Wake Forest University School of Medicine, Charlotte, NC 28204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiz","family":"Anwer","sequence":"additional","affiliation":[{"name":"US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS 66205, USA"},{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2739-2265","authenticated-orcid":false,"given":"Shahzad","family":"Raza","sequence":"additional","affiliation":[{"name":"US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS 66205, USA"},{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aytaj","family":"Mammadzadeh","sequence":"additional","affiliation":[{"name":"US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS 66205, USA"},{"name":"Division of Hematology and Oncology, Mayo Clinic, Rochester, MN 44905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7531-1178","authenticated-orcid":false,"given":"Bayan","family":"Khasawneh","sequence":"additional","affiliation":[{"name":"US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS 66205, USA"},{"name":"Department of Internal Medicine, Jordan University of Science & Technology, Irbid 22110, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Shatnawi","sequence":"additional","affiliation":[{"name":"US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS 66205, USA"},{"name":"Department of Internal Medicine, Jordan University of Science & Technology, Irbid 22110, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"McGuirk","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4336-4982","authenticated-orcid":false,"given":"Nausheen","family":"Ahmed","sequence":"additional","affiliation":[{"name":"US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS 66205, USA"},{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Mahmoudjafari","sequence":"additional","affiliation":[{"name":"US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS 66205, USA"},{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Mushtaq","sequence":"additional","affiliation":[{"name":"US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS 66205, USA"},{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Al-Ola","family":"Abdallah","sequence":"additional","affiliation":[{"name":"US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS 66205, USA"},{"name":"Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4547-7534","authenticated-orcid":false,"given":"Shebli","family":"Atrash","sequence":"additional","affiliation":[{"name":"US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS 66205, USA"},{"name":"Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health Wake Forest University School of Medicine, Charlotte, NC 28204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2022","journal-title":"CA A Cancer J. 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Lymphoma"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1056\/NEJMoa2204925","article-title":"Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma","volume":"387","author":"Richardson","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1056\/NEJMoa1611750","article-title":"Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma","volume":"376","author":"Attal","year":"2017","journal-title":"N. Engl. J. 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J. Haematol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/17\/2938\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:42:16Z","timestamp":1760110936000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/17\/2938"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,23]]},"references-count":44,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["cancers16172938"],"URL":"https:\/\/doi.org\/10.3390\/cancers16172938","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,23]]}}}