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We report the final analysis of a single\u2010arm, phase 2 study evaluating the oral proteasome inhibitor (PI) ixazomib combined with daratumumab and dexamethasone (IDd; NCT03439293). Sixty\u2010one RRMM patients (ixazomib\/daratumumab\u2010na\u00efve; 1\u20133 prior therapies) were enrolled to receive IDd (28\u2010day\u2009cycles) until disease progression\/unacceptable toxicity. Median age was 69\u2009years; 14.8% of patients had International Staging System stage III disease; 14.8% had received three prior therapies. Patients received a median of 16\u2009cycles of IDd. In 59 response\u2010evaluable patients, the overall response rate was 64.4%; the confirmed \u2265very good partial response (VGPR) rate (primary endpoint) was 30.5%. Rates of \u2265VGPR in patient subgroups were: high\u2010risk cytogenetics (<jats:italic>n<\/jats:italic>\u2009=\u200915, 26.7%), expanded high\u2010risk cytogenetics (<jats:italic>n<\/jats:italic>\u2009=\u200924, 29.2%), aged \u226575\u2009years (<jats:italic>n<\/jats:italic>\u2009=\u200912, 16.7%), lenalidomide\u2010refractory (<jats:italic>n<\/jats:italic>\u2009=\u200921, 28.6%), and prior PI\/IMiD therapy (<jats:italic>n<\/jats:italic>\u2009=\u200958, 31.0%). With a median follow\u2010up of 31.6\u2009months, median progression\u2010free survival was 16.8\u2009months (95% confidence interval: 10.1\u201323.7). Grade \u22653 treatment\u2010emergent adverse events (TEAEs) occurred in 54.1% of patients; 44.3% had serious TEAEs; TEAEs led to dose modifications\/reductions\/discontinuations in 62.3%\/36.1%\/16.4%. There were five on\u2010study deaths. Any\u2010grade and grade \u22653 peripheral neuropathy occurred in 18.0% and 1.6% of patients. Quality of life was generally maintained throughout treatment. IDd showed a positive risk\u2010benefit profile in RRMM patients and was active in clinically relevant subgroups with no new safety signals.<\/jats:p>","DOI":"10.1002\/ajh.27382","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T12:34:51Z","timestamp":1718022891000},"page":"1746-1756","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ixazomib plus daratumumab and dexamethasone: Final analysis of a phase 2 study among patients with relapsed\/refractory multiple myeloma"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7523-7510","authenticated-orcid":false,"given":"Sosana","family":"Delimpasi","sequence":"first","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation Unit General Hospital Evangelismos  Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-3254","authenticated-orcid":false,"given":"Meletios A.","family":"Dimopoulos","sequence":"additional","affiliation":[{"name":"Hematology &amp; Medical Oncology, Department of Clinical Therapeutics National and Kapodistrian University of Athens, School of Medicine  Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Straub","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine \u2013 Hematology University Hospital  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-3473","authenticated-orcid":false,"given":"Argiris","family":"Symeonidis","sequence":"additional","affiliation":[{"name":"Department of Hematology University General Hospital of Patras  Patras Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lud\u011bk","family":"Pour","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hematology and Oncology University Hospital Brno  Brno Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"H\u00e1jek","sequence":"additional","affiliation":[{"name":"Department of Haematooncology, University Hospital Ostrava and Department of Haematooncology, Faculty of Medicine University of Ostrava  Ostrava Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyrille","family":"Touzeau","sequence":"additional","affiliation":[{"name":"University Hospital H\u00f4tel Dieu  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viralkumar K.","family":"Bhanderi","sequence":"additional","affiliation":[{"name":"Florida Cancer Specialists Tallahassee Cancer Center  Tallahassee Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4362-0376","authenticated-orcid":false,"given":"Jesus G.","family":"Berdeja","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Pavl\u00ed\u010dek","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Hematology University Hospital Kralovske Vinohrady  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey V.","family":"Matous","sequence":"additional","affiliation":[{"name":"Colorado Blood Cancer Institute and Sarah Cannon Research Institute  Denver Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawel J.","family":"Robak","sequence":"additional","affiliation":[{"name":"Department of Hematology Medical University of Lodz and Copernicus Memorial Hospital  Lodz Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaveri","family":"Suryanarayan","sequence":"additional","affiliation":[{"name":"Clinical Research Takeda Development Center Americas, Inc. 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