{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:07:14Z","timestamp":1789387634749,"version":"build-2803163510"},"reference-count":42,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Hematology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multiple myeloma (MM) is the second most common hematologic malignancy worldwide. Recent therapeutic innovations, including the addition of daratumumab to standard regimens, have shown promising improvements in patient outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aims to compare the efficacy and safety of daratumumab-based quadruplet therapy regimens with standard triplet therapy regimens in newly diagnosed multiple myeloma (NDMM) patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Systematic review and meta-analysis of randomized controlled trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources and Methods<\/jats:title>\n                    <jats:p>A comprehensive literature search was conducted on PubMed, Cochrane Library, Embase, and ClinicalTrials.gov from inception to April 2026. Primary outcomes were Progression-free survival (PFS) and Minimal residual disease (MRD) negativity. Subgroup analysis based on cytogenetic risk was performed. The statistical assessment was done using The Review Manager (RevMan, Version 5.4).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our meta-analysis included 7 RCTs, comprising 3 studies in transplant-eligible multiple myeloma (TE-MM) and 4 in transplant-ineligible multiple myeloma (TIE-MM) patients, containing 3,443 patients (1,759 in the daratumumab group and 1684 in the non-daratumumab group). The median age across studies ranged from approximately 59 to 76 years. Daratumumab-based therapy demonstrated significantly higher PFS (HR 0.50, 95%CI: 0.43- 0.58, p &lt; 0.00001). The analysis showed statistically significant high MRD negativity with daratumumab based quadruplet therapy compared to non-Dara triplet arm (RR 1.99, 95%CI 1.59-2.50, P&lt;0.00001). Subgroup analysis based on cytogenetic risk demonstrated significant improved PFS in standard-risk (HR 0.45) as well as high-risk (HR 0.67), whereas MRD negativity increased significantly only in standard-risk (RR 1.76) but not high-risk (RR 1.23). Daratumumab-based quadruplet therapy was associated with increased neutropenia (56.2% vs 40.3%), thrombocytopenia (40.7% vs 32.5%), and infections (33.1% vs 23.3%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The meta-analysis shows higher efficacy yet higher adverse events in Daratumumab-based quadruplet therapy for NDMM patients (TE, and TIE).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/20406207261489040","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T21:34:22Z","timestamp":1789162462000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of daratumumab-based quadruplet therapy vs non-daratumumab-based triplet therapy in newly diagnosed multiple myeloma patients: A GRADE assessed systematic review and meta-analysis of randomized controlled trials"],"prefix":"10.1177","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0197-4264","authenticated-orcid":false,"given":"Muhammad","family":"Osama","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Khyber Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Haris","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Saidu Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammara","family":"Tahir","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Liaquat University of Medical and Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Liaquat University of Medical and Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Iftikhar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, The University of Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizaz","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Khyber Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safeena","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Khyber Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malak","family":"Bilal Hassan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Saidu Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Intikhab","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Saidu Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4563-7760","authenticated-orcid":false,"given":"Zeeshan","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Saidu Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Afridi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Khyber Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Ebad Ur Rehman","sequence":"additional","affiliation":[{"name":"Rawalpindi Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna","family":"Gul","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Liaquat National Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawan Kumar","family":"Thada","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Sotang Primary Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-078022"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25117"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-071548"},{"key":"e_1_3_7_5_2","volume-title":"Silver Spring (MD)","author":"U.S. Food and Drug Administration","year":"2019","unstructured":"U.S. Food and Drug Administration. 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