Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma
Copyright © 2023 Massachusetts Medical Society..
BACKGROUND: Daratumumab, a monoclonal antibody targeting CD38, has been approved for use with standard myeloma regimens. An evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients with newly diagnosed multiple myeloma is needed.
METHODS: In this phase 3 trial, we randomly assigned 709 transplantation-eligible patients with newly diagnosed multiple myeloma to receive either subcutaneous daratumumab combined with VRd induction and consolidation therapy and with lenalidomide maintenance therapy (D-VRd group) or VRd induction and consolidation therapy and lenalidomide maintenance therapy alone (VRd group). The primary end point was progression-free survival. Key secondary end points were a complete response or better and minimal residual disease (MRD)-negative status.
RESULTS: At a median follow-up of 47.5 months, the risk of disease progression or death in the D-VRd group was lower than the risk in the VRd group. The estimated percentage of patients with progression-free survival at 48 months was 84.3% in the D-VRd group and 67.7% in the VRd group (hazard ratio for disease progression or death, 0.42; 95% confidence interval, 0.30 to 0.59; P<0.001); the P value crossed the prespecified stopping boundary (P = 0.0126). The percentage of patients with a complete response or better was higher in the D-VRd group than in the VRd group (87.9% vs. 70.1%, P<0.001), as was the percentage of patients with MRD-negative status (75.2% vs. 47.5%, P<0.001). Death occurred in 34 patients in the D-VRd group and 44 patients in the VRd group. Grade 3 or 4 adverse events occurred in most patients in both groups; the most common were neutropenia (62.1% with D-VRd and 51.0% with VRd) and thrombocytopenia (29.1% and 17.3%, respectively). Serious adverse events occurred in 57.0% of the patients in the D-VRd group and 49.3% of those in the VRd group.
CONCLUSIONS: The addition of subcutaneous daratumumab to VRd induction and consolidation therapy and to lenalidomide maintenance therapy conferred a significant benefit with respect to progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma. (Funded by the European Myeloma Network in collaboration with Janssen Research and Development; PERSEUS ClinicalTrials.gov number, NCT03710603; EudraCT number, 2018-002992-16.).
| Errataetall: |
CommentIn: N Engl J Med. 2024 Apr 18;390(15):1440. - PMID 38631009 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:390 |
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| Enthalten in: |
The New England journal of medicine - 390(2024), 4 vom: 25. Jan., Seite 301-313 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sonneveld, Pieter [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.01.2024 Date Revised 17.04.2024 published: Print-Electronic ClinicalTrials.gov: NCT03710603 EudraCT: 2018-002992-16 CommentIn: N Engl J Med. 2024 Apr 18;390(15):1440. - PMID 38631009 Citation Status MEDLINE |
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| doi: |
10.1056/NEJMoa2312054 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma |
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| 500 | |a Date Revised 17.04.2024 | ||
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| 500 | |a ClinicalTrials.gov: NCT03710603 | ||
| 500 | |a EudraCT: 2018-002992-16 | ||
| 500 | |a CommentIn: N Engl J Med. 2024 Apr 18;390(15):1440. - PMID 38631009 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Massachusetts Medical Society. | ||
| 520 | |a BACKGROUND: Daratumumab, a monoclonal antibody targeting CD38, has been approved for use with standard myeloma regimens. An evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients with newly diagnosed multiple myeloma is needed | ||
| 520 | |a METHODS: In this phase 3 trial, we randomly assigned 709 transplantation-eligible patients with newly diagnosed multiple myeloma to receive either subcutaneous daratumumab combined with VRd induction and consolidation therapy and with lenalidomide maintenance therapy (D-VRd group) or VRd induction and consolidation therapy and lenalidomide maintenance therapy alone (VRd group). The primary end point was progression-free survival. Key secondary end points were a complete response or better and minimal residual disease (MRD)-negative status | ||
| 520 | |a RESULTS: At a median follow-up of 47.5 months, the risk of disease progression or death in the D-VRd group was lower than the risk in the VRd group. The estimated percentage of patients with progression-free survival at 48 months was 84.3% in the D-VRd group and 67.7% in the VRd group (hazard ratio for disease progression or death, 0.42; 95% confidence interval, 0.30 to 0.59; P<0.001); the P value crossed the prespecified stopping boundary (P = 0.0126). The percentage of patients with a complete response or better was higher in the D-VRd group than in the VRd group (87.9% vs. 70.1%, P<0.001), as was the percentage of patients with MRD-negative status (75.2% vs. 47.5%, P<0.001). Death occurred in 34 patients in the D-VRd group and 44 patients in the VRd group. Grade 3 or 4 adverse events occurred in most patients in both groups; the most common were neutropenia (62.1% with D-VRd and 51.0% with VRd) and thrombocytopenia (29.1% and 17.3%, respectively). Serious adverse events occurred in 57.0% of the patients in the D-VRd group and 49.3% of those in the VRd group | ||
| 520 | |a CONCLUSIONS: The addition of subcutaneous daratumumab to VRd induction and consolidation therapy and to lenalidomide maintenance therapy conferred a significant benefit with respect to progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma. (Funded by the European Myeloma Network in collaboration with Janssen Research and Development; PERSEUS ClinicalTrials.gov number, NCT03710603; EudraCT number, 2018-002992-16.) | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Lonergan, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmadi, Tahamtan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yanfang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jianping |e verfasserin |4 aut | |
| 700 | 1 | |a Vieyra, Diego |e verfasserin |4 aut | |
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