{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T21:24:09Z","timestamp":1777411449336,"version":"3.51.4"},"reference-count":26,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"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>Background: Treatment of multiple myeloma has advanced tremendously with the approval of anti-CD38 antibodies. Their efficacy is impressive but still controversial in the 1q amplification subgroup (amp1q). This retrospective study aims to provide real-world data. Methods: This trial is analyzing 74 patients with relapsed\/refractory multiple myeloma treated with CD38Abs at the Medical University of Innsbruck (2016\u20132023). High-risk (HR) cytogenetics according to R-ISS (t(4;14), t(14;16), t(14;20), del(17p)), the presence of amp(1q21), the frequency of two HR markers (double hit), and the high-risk criteria agreed at IMS 2024 (HR-IMS24) were considered. Results: The median age of the 74 patients (62.1% male) was 62 years, with a median follow-up of six years. Most patients received third-line therapy (37.8%). R-ISS HR was documented in 39.2% of patients, double hit in 13.5% of patients, and HR-IMS24 in 32.4% of patients, while amp1q was detected in 35.1% of patients. The median OS was 66 months (35\u201389), and the median PFS was 17 months (6.5\u201326.9). While neither R-ISS HR nor isolated amp1q had an impact on progression-free survival (e.g., amp1q 7.03: 1.95\u201322.44; p = 0.347), the occurrence of a double-hit pattern significantly impaired PFS and OS (6.2: 1.4\u201316.4 months; p = 0.044; OS, 42.8: 25.9\u201374.6 months; p = 0.035). Patients fulfilling the HR-IMS24 criteria (32.4%, 24 patients) also exhibited an impaired PFS and OS (7: 2.7\u201318.1 months, p = 0.023; 40.12: 21.1\u201374.5 months, p = 0.01). Conclusions: This retrospective study highlights the durable effect of daratumumab on cytogenetic abnormalities, particularly amp1q. However, patients who meet the criteria for double-hit myeloma or the high-risk IMS2024 criteria remain a difficult-to-treat patient population who require early access to new treatment approaches.<\/jats:p>","DOI":"10.3390\/cancers17081261","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T03:32:53Z","timestamp":1744169573000},"page":"1261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Real-World Data on the Efficacy of Daratumumab in Patients with Relapsed\/Refractory Multiple Myeloma and Amplification 1q"],"prefix":"10.3390","volume":"17","author":[{"given":"Magdalena","family":"Benda","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II, Feldkirch Academic Teaching Hospital, 6800 Feldkirch, Austria"},{"name":"Faculty of Medical Sciences, Private University of the Principality of Liechtenstein, 9459 Triesen, Liechtenstein"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Reimann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Feldkirch Academic Teaching Hospital, 6800 Feldkirch, Austria"},{"name":"Faculty of Medical Sciences, Private University of the Principality of Liechtenstein, 9459 Triesen, Liechtenstein"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Bletzacher","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Muendlein","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, Vorarlberg Institute for Vascular Investigation and Treatment, 6850 Dornbirn, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benda","family":"Bernhard","sequence":"additional","affiliation":[{"name":"Core Facility Internal Emergency and Intensive Care Medicine, University Clinic Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Feldkirch Academic Teaching Hospital, 6800 Feldkirch, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minh","family":"Huynh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Feldkirch Academic Teaching Hospital, 6800 Feldkirch, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Gasser","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Feldkirch Academic Teaching Hospital, 6800 Feldkirch, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niklas","family":"Zojer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Feldkirch Academic Teaching Hospital, 6800 Feldkirch, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresia","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Feldkirch Academic Teaching Hospital, 6800 Feldkirch, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"G\u00f6bel","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Paul","family":"Bohn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eberhard","family":"Gunsilius","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Nachbaur","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emina","family":"Jukic","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurus","family":"Locher","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical University of Innsbruck, 6020 Innsbruck, Austria"},{"name":"Department of Human Genetics, Inselspital Bern, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ella","family":"Willenbacher","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Willenbacher","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, 6020 Innsbruck, Austria"},{"name":"Syndena GmbH, Connect to Cure, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Winder","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Feldkirch Academic Teaching Hospital, 6800 Feldkirch, Austria"},{"name":"University of Zurich, 8006 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Normann","family":"Steiner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1002\/ajh.27422","article-title":"Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management","volume":"99","author":"Rajkumar","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.clml.2019.09.623","article-title":"Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR","volume":"20","author":"Mateos","year":"2020","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1200\/JCO.22.00940","article-title":"Overall Survival With Daratumumab, Lenalidomide, and Dexamethasone in Previously Treated Multiple Myeloma (POLLUX): A Randomized, Open-Label, Phase III Trial","volume":"41","author":"Dimopoulos","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/S1470-2045(21)00466-6","article-title":"Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): Overall survival results from a randomised, open-label, phase 3 trial","volume":"22","author":"Facon","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.3324\/haematol.2022.280660","article-title":"Primary outcomes by 1q21+ status for isatuximab-treated patients with relapsed\/refractory multiple myeloma: Subgroup analyses from ICARIA-MM and IKEMA","volume":"107","author":"Martin","year":"2022","journal-title":"Haematologica"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1056\/NEJMoa2312054","article-title":"Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma","volume":"390","author":"Sonneveld","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41408-024-01045-3","article-title":"Final analysis of a phase II trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma without transplant","volume":"14","author":"Derman","year":"2024","journal-title":"Blood Cancer J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(19)31240-1","article-title":"Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): A randomised, open-label, phase 3 study","volume":"394","author":"Moreau","year":"2019","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1200\/JCO.21.01935","article-title":"Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone with Minimal Residual Disease Response-Adapted Therapy in Newly Diagnosed Multiple Myeloma","volume":"40","author":"Costa","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1056\/NEJMoa2400712","article-title":"Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma","volume":"391","author":"Facon","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12962-024-00525-4","article-title":"Cost-effectiveness and budget impact analysis of Daratumumab, Lenalidomide and dexamethasone for relapsed-refractory multiple myeloma","volume":"22","author":"Goudarzi","year":"2024","journal-title":"Cost Eff. Resour. Alloc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1080\/17474086.2021.1983427","article-title":"Chromosomal 1q21 abnormalities in multiple myeloma: A review of translational, clinical research, and therapeutic strategies","volume":"14","author":"Bisht","year":"2021","journal-title":"Expert Rev. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1200\/JCO.21.02614","article-title":"Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY Project","volume":"40","author":"Cairns","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_14","unstructured":"Kort\u00fcm, M., Auner, H.W., Bassermann, F., Driessen, C., Einsele, H., Engelhardt, M., Goldschmidt, H., Gunsilius, E., Krauth, M.T., and Kraywinkel, K. (2025, March 26). Multiple Myeloma. Onkopedia. Available online: https:\/\/www.onkopedia.com\/de\/onkopedia\/guidelines\/multiples-myelom\/@@guideline\/html\/index.html#ID0E5OAI."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/bjh.16292","article-title":"Daratumumab in high-risk relapsed\/refractory multiple myeloma patients: Adverse effect of chromosome 1q21 gain\/amplification and GEP70 status on outcome","volume":"189","author":"Mohan","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/bjh.17499","article-title":"Subgroup analysis of ICARIA-MM study in relapsed\/refractory multiple myeloma patients with high-risk cytogenetics","volume":"194","author":"Harrison","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhu, C., Song, Z., Wang, A., Srinivasan, S., Yang, G., Greco, R., Theilhaber, J., Shehu, E., Wu, L., and Yang, Z.-Y. (2020). Isatuximab Acts Through Fc-Dependent, Independent, and Direct Pathways to Kill Multiple Myeloma Cells. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01771"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1182\/blood-2016-03-703439","article-title":"CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma","volume":"128","author":"Nijhof","year":"2016","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1158\/2326-6066.CIR-15-0055","article-title":"T-cell Exhaustion in Multiple Myeloma Relapse after Autotransplant: Optimal Timing of Immunotherapy","volume":"4","author":"Chung","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1182\/blood-2015-12-687749","article-title":"Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma","volume":"128","author":"Krejcik","year":"2016","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1182\/blood-2015-01-625004","article-title":"Lenalidomide augments actin remodeling and lowers NK-cell activation thresholds","volume":"126","author":"Lagrue","year":"2015","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7237","DOI":"10.1182\/blood-2022-169533","article-title":"Therapeutic Outcomes of Relapsed-Refractory Multiple Myeloma Patients with 1q21+Treated with Daratumumab-Based Regimens: A Retrospective Analysis","volume":"140","author":"Parrondo","year":"2022","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/S0140-6736(21)00592-4","article-title":"Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): A multicentre, open-label, randomised phase 3 trial","volume":"397","author":"Moreau","year":"2021","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.1182\/blood-2023-173896","article-title":"Impact of 1q21 Gain and Amplification on Daratumumab-Treated Multiple Myeloma Patients: Real-World Data from the Australia-New Zealand and Asia-Pacific Myeloma and Related Diseases Registries","volume":"142","author":"Lim","year":"2023","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1200\/JCO.23.01696","article-title":"Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma","volume":"42","author":"Leypoldt","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_26","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."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/8\/1261\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:12:42Z","timestamp":1760029962000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/8\/1261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,8]]},"references-count":26,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["cancers17081261"],"URL":"https:\/\/doi.org\/10.3390\/cancers17081261","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,8]]}}}