{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:21:25Z","timestamp":1789676485679,"version":"4.0.1"},"reference-count":24,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Janssen-CILAG"},{"name":"University Medical Center Hamburg-Eppendorf"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Renal function impairment (RI) is a common complication in multiple myeloma (MM). However, limited data exist on the safety and efficacy of anti-MM regimens in patients with severe RI, as these patients are frequently excluded from clinical trials. This investigator-initiated multicentric phase II GMMG-DANTE trial evaluated daratumumab, bortezomib, and dexamethasone (DVd) in relapsed or refractory (r\/r) MM patients with severe RI. r\/rMM patients with \u22651 prior treatment line and a GFR &lt;30 mL\/min\/1.73 m2 or undergoing hemodialysis were eligible and received eight cycles of DVd followed by daratumumab maintenance. The trial closed prematurely after 22\/36 planned patients. The primary endpoint was overall response rate (ORR). Median age of patients was 70 (range 55\u201389) years, with a median GFR of 20.1 mL\/min\/1.73 m2 (interquartile range, 9.4\u201327.3 mL\/min\/1.73 m2), and eight patients under hemodialysis. Median number of prior lines was two (range 1\u201310). The trial was successful, albeit with premature termination, as it met its primary endpoint, with an ORR of 67% (14\/21). The rates of partial response, very good partial response, and complete response were 29%, 29%, and 10%, respectively (n = 6, 6, and 2). Fourteen patients (67%) achieved renal response. After median follow-up of 28 months, median progression-free survival was 10.4 months; median overall survival was not reached. Higher-grade toxicity was mainly hematologic, and non-hematologic toxicities \u2265Grade 3 were mostly infections (24%). The prospective GMMG-DANTE trial investigating DVd exclusively in r\/rMM patients with severe RI showed efficacy and safety to be comparable to data from patients without RI.<\/jats:p>","DOI":"10.3390\/cancers15184667","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T21:16:49Z","timestamp":1695331009000},"page":"4667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Daratumumab, Bortezomib, and Dexamethasone for Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Severe Renal Impairment: Results from the Phase 2 GMMG-DANTE Trial"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9248-588X","authenticated-orcid":false,"given":"Lisa B.","family":"Leypoldt","sequence":"first","affiliation":[{"name":"Department of Hematology, Oncology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gavriatopoulou","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, Alexandra General Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Besemer","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Immunology, Rheumatology, University Hospital of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7803-0814","authenticated-orcid":false,"given":"Hans","family":"Salwender","sequence":"additional","affiliation":[{"name":"Asklepios Tumorzentrum Hamburg, AK Altona and AK St. Georg, 22763 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Raab","sequence":"additional","affiliation":[{"name":"Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Nogai","sequence":"additional","affiliation":[{"name":"Medizinische Klinik m.S. H\u00e4matologie, Onkologie und Tumorimmunologie, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 12200 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4655-6269","authenticated-orcid":false,"given":"Cyrus","family":"Khandanpour","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"},{"name":"Department of Hematology and Oncology, University Hospital Schleswig-Holstein and University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Runde","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Palliative Care, Wilhelm-Anton-Hospital, 47574 Goch, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Jauch","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manola","family":"Zago","sequence":"additional","affiliation":[{"name":"Center for Clinical Trials, University Hospital of Tuebingen, 72070 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Martus","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology and Applied Biostatistics, Eberhard Karls University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0961-0035","authenticated-orcid":false,"given":"Hartmut","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Internal Medicine V and GMMG-Study Group, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Bokemeyer","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-3254","authenticated-orcid":false,"given":"Meletios A.","family":"Dimopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, Alexandra General Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja C.","family":"Weisel","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/annonc\/mdt483","article-title":"Significant improvement in the survival of patients with multiple myeloma presenting with severe renal impairment after the introduction of novel agents","volume":"25","author":"Dimopoulos","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrneph.2012.14","article-title":"Novel approaches for reducing free light chains in patients with myeloma kidney","volume":"8","author":"Hutchison","year":"2012","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.1182\/blood-2003-03-0801","article-title":"Long-term follow-up of IgM monoclonal gammopathy of undetermined significance","volume":"102","author":"Kyle","year":"2003","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1093\/ndt\/gfp679","article-title":"Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: An ERA-EDTA Registry study","volume":"25","author":"Tsakiris","year":"2010","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1200\/JCO.2015.65.0044","article-title":"International Myeloma Working Group Recommendations for the Diagnosis and Management of Myeloma-Related Renal Impairment","volume":"34","author":"Dimopoulos","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Uttervall, K., Duru, A.D., Lund, J., Liwing, J., Gahrton, G., Holmberg, E., Aschan, J., Alici, E., and Nahi, H. (2014). The use of novel drugs can effectively improve response, delay relapse and enhance overall survival in multiple myeloma patients with renal impairment. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101819"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bozic, B., Rutner, J., Zheng, C., Ruckser, R., Selimi, F., Racz, K., Kocher, M., Tatzreiter, G., and Sebesta, C. (2021). Advances in the Treatment of Relapsed and Refractory Multiple Myeloma in Patients with Renal Insufficiency: Novel Agents, Immunotherapies and Beyond. Cancers, 13.","DOI":"10.3390\/cancers13205036"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e293","DOI":"10.1016\/S1470-2045(23)00223-1","article-title":"Management of multiple myeloma-related renal impairment: Recommendations from the International Myeloma Working Group","volume":"24","author":"Dimopoulos","year":"2023","journal-title":"Lancet Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/leu.2012.182","article-title":"The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma","volume":"27","author":"Dimopoulos","year":"2013","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.3324\/haematol.2018.194282","article-title":"Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: Updated analysis of POLLUX","volume":"103","author":"Dimopoulos","year":"2018","journal-title":"Haematologica"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1182\/blood-2016-03-705210","article-title":"Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma","volume":"128","author":"Usmani","year":"2016","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1056\/NEJMoa1606038","article-title":"Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma","volume":"375","author":"Palumbo","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1056\/NEJMoa1817249","article-title":"Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma","volume":"380","author":"Facon","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/S0140-6736(20)30734-0","article-title":"Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): Results from a randomised, multicentre, open-label, phase 3 study","volume":"396","author":"Dimopoulos","year":"2020","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1373\/clinchem.2006.077180","article-title":"Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values","volume":"53","author":"Levey","year":"2007","journal-title":"Clin. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e538","DOI":"10.1016\/S1470-2045(14)70442-5","article-title":"International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma","volume":"15","author":"Rajkumar","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1080\/10428194.2020.1867725","article-title":"Renal insufficiency in multiple myeloma: A systematic review and meta-analysis of all randomized trials from 2005-2019","volume":"62","author":"Mohyuddin","year":"2021","journal-title":"Leuk. Lymphoma"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1200\/JCO.2017.76.1742","article-title":"Pomalidomide Plus Low-Dose Dexamethasone in Patients With Relapsed\/Refractory Multiple Myeloma and Renal Impairment: Results From a Phase II Trial","volume":"36","author":"Dimopoulos","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E226","DOI":"10.1002\/ajh.27001","article-title":"Prospective phase 2 trial of daratumumab with dexamethasone in patients with relapsed\/refractory multiple myeloma and severe renal impairment or on dialysis: The DARE study","volume":"98","author":"Kastritis","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/s41375-020-0868-z","article-title":"Isatuximab plus pomalidomide and dexamethasone in relapsed\/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis","volume":"35","author":"Dimopoulos","year":"2020","journal-title":"Leukemia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.3324\/haematol.2021.279229","article-title":"Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis","volume":"107","author":"Capra","year":"2022","journal-title":"Haematologica"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1016\/S0140-6736(19)32556-5","article-title":"Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): A randomised, multicentre, open-label, phase 3 study","volume":"394","author":"Attal","year":"2019","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41408-022-00758-7","article-title":"Bortezomib, Bendamustine and Dexamethasone vs Thalidomide, Bendamustine and Dexamethasone in Myeloma patients presenting with renal failure (OPTIMAL): A randomised, multi-centre phase II trial","volume":"12","author":"Ramasamy","year":"2022","journal-title":"Blood Cancer J."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/18\/4667\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:55:07Z","timestamp":1760129707000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/18\/4667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,21]]},"references-count":24,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cancers15184667"],"URL":"https:\/\/doi.org\/10.3390\/cancers15184667","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,21]]}}}