TY - JOUR
T1 - 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
AU - Moreau, Philippe
AU - Attal, Michel
AU - Hulin, Cyrille
AU - Arnulf, Bertrand
AU - Belhadj, K.
AU - Benboubker, L.
AU - Béné, Marie C.
AU - Broijl, Annemiek
AU - Caillon, H. lène
AU - Caillot, D.
AU - Corre, Jill
AU - Delforge, Michel
AU - Dejoie, Thomas
AU - Doyen, Chantal
AU - Facon, Thierry
AU - Sonntag, C. cile
AU - Fontan, Jean
AU - Garderet, Laurent
AU - Jie, Kon-Siong
AU - Karlin, Lionel
AU - Kuhnowski, Frédérique
AU - Lambert, J. rôme
AU - Leleu, Xavier
AU - Lenain, Pascal
AU - Macro, Margaret
AU - Mathiot, Claire
AU - Orsini-Piocelle, Frédérique
AU - Perrot, Aurore
AU - Stoppa, Anne-Marie
AU - van de Donk, Niels W. CJ
AU - Wuilleme, Soraya
AU - Zweegman, S.
AU - Kolb, Brigitte
AU - Touzeau, Cyrille
AU - Roussel, Murielle
AU - Tiab, Mourad
AU - Marolleau, Jean-Pierre
AU - Meuleman, Nathalie
AU - Vekemans, Marie-Christiane
AU - Westerman, Matthijs
AU - Klein, Saskia K.
AU - Levin, Mark-David
AU - Fermand, Jean Paul
AU - Escoffre-Barbe, Martine
AU - Eveillard, Jean-Richard
AU - Garidi, Reda
AU - Ahmadi, Tahamtan
AU - Zhuang, Sen
AU - Chiu, Christopher
AU - Pei, L.
AU - de Boer, C.
AU - Smith, E.
AU - Deraedt, William
AU - Kampfenkel, Tobias
AU - Schecter, Jordan
AU - Vermeulen, Jessica
AU - Avet-Loiseau, Hervé
AU - Sonneveld, Pieter
PY - 2019/7/6
Y1 - 2019/7/6
N2 - Background: Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma. Methods: In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Findings: Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10−5 sensitivity threshold, assessed by multiparametric flow cytometry; both p<0·0001). Median progression-free survival from first randomisation was not reached in either group (hazard ratio 0·47, 95% CI 0·33–0·67, p<0·0001). 46 deaths on study were observed (14 vs 32, 0·43, 95% CI 0·23–0·80). The most common grade 3 or 4 adverse events were neutropenia (28% vs 15%), lymphopenia (17% vs 10%), and stomatitis (13% vs 16%). Interpretation: D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple myeloma. Funding: The Intergroupe Francophone du Myélome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
AB - Background: Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma. Methods: In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. Findings: Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10−5 sensitivity threshold, assessed by multiparametric flow cytometry; both p<0·0001). Median progression-free survival from first randomisation was not reached in either group (hazard ratio 0·47, 95% CI 0·33–0·67, p<0·0001). 46 deaths on study were observed (14 vs 32, 0·43, 95% CI 0·23–0·80). The most common grade 3 or 4 adverse events were neutropenia (28% vs 15%), lymphopenia (17% vs 10%), and stomatitis (13% vs 16%). Interpretation: D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple myeloma. Funding: The Intergroupe Francophone du Myélome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85066411224&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31171419
U2 - https://doi.org/10.1016/S0140-6736(19)31240-1
DO - https://doi.org/10.1016/S0140-6736(19)31240-1
M3 - Article
C2 - 31171419
SN - 0140-6736
VL - 394
SP - 29
EP - 38
JO - The Lancet
JF - The Lancet
IS - 10192
ER -