000182424 001__ 182424 000182424 005__ 20240229145718.0 000182424 0247_ $$2doi$$a10.1016/S2352-3026(22)00263-0 000182424 0247_ $$2pmid$$apmid:36328040 000182424 0247_ $$2ISSN$$a2352-3026 000182424 0247_ $$2ISSN$$a2451-9960 000182424 0247_ $$2altmetric$$aaltmetric:137943718 000182424 037__ $$aDKFZ-2022-02633 000182424 041__ $$aEnglish 000182424 082__ $$a610 000182424 1001_ $$aGoldschmidt, Hartmut$$b0 000182424 245__ $$aAddition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial. 000182424 260__ $$aLondon [u.a.]$$bElsevier$$c2022 000182424 3367_ $$2DRIVER$$aarticle 000182424 3367_ $$2DataCite$$aOutput Types/Journal article 000182424 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1667815427_16149 000182424 3367_ $$2BibTeX$$aARTICLE 000182424 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000182424 3367_ $$00$$2EndNote$$aJournal Article 000182424 520__ $$aAnti-CD38 monoclonal antibodies have consistently shown increased efficacy when added to standard of care for patients with multiple myeloma. We aimed to assess the efficacy of isatuximab in addition to lenalidomide, bortezomib, and dexamethasone in patients with newly diagnosed transplantation-eligible multiple myeloma.This open-label, multicentre, randomised, active-controlled, phase 3 trial was done at 67 academic and oncology practice centres in Germany. This study is ongoing and divided into two parts; herein, we report results from part 1. Eligible patients were aged 18-70 years; had a confirmed diagnosis of untreated multiple myeloma requiring systemic treatment and a WHO performance status of 0-2; and were eligible for induction therapy, high-dose melphalan and autologous haematopoietic stem-cell transplantation, and maintenance treatment. Patients were randomly assigned (1:1) to receive three 42-day cycles of induction therapy either with isatuximab plus lenalidomide, bortezomib, and dexamethasone (isatuximab group) or lenalidomide, bortezomib, and dexamethasone alone (control group) using a web-based system and permuted blocks. Patients in both groups received lenalidomide (25 mg orally on days 1-14 and 22-35), bortezomib (1·3 mg/m2 subcutaneously on days 1, 4, 8, 11, 22, 25, 29, and 32), and dexamethasone (20 mg orally on days 1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, and 32-33). Isatuximab was given as 10 mg/kg intravenously on days 1, 8, 15, 22, and 29 of cycle 1 and on days 1, 15, and 29 of cycles 2 and 3. The primary endpoint was minimal residual disease (MRD) negativity assessed by flow cytometry, in the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov, NCT03617731.Between Oct 23, 2018, and Sep 22, 2020, 660 patients were included in the ITT analysis (331 in the isatuximab group and 329 in the control group). 654 (99%) patients were White, two were African, one was Arabic, and three were Asian. 250 (38%) were women and 410 (62%) were men. The median age was 59 years (IQR 54-64). MRD negativity after induction therapy was reached in 166 (50%) patients in the isatuximab group versus 117 (36%) in the control group (OR 1·82 [95% CI 1·33-2·48]; p=0·00017). Median follow-up time from start to end of induction therapy was 125 days (IQR 125-131) versus 125 days (125-132). At least one grade 3 or 4 adverse event occurred in 208 (63%) of 330 patients versus 199 (61%) of 328 patients. Neutropenia of grade 3 or 4 occurred in 77 (23%) versus 23 (7%) patients and infections of grade 3 or 4 occurred in 40 (12%) versus 32 (10%) patients. Among 12 deaths during induction therapy, one death due to septic shock in the isatuximab group and four deaths (one cardiac decompensation, one hepatic and renal failure, one cardiac arrest, and one drug-induced enteritis) in the control group were considered treatment-related.Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone for induction therapy improved rates of MRD negativity with no new safety signals in patients with newly diagnosed transplantation-eligible multiple myeloma.Sanofi and Bristol Myers Squibb (Celgene). 000182424 536__ $$0G:(DE-HGF)POF4-313$$a313 - Krebsrisikofaktoren und Prävention (POF4-313)$$cPOF4-313$$fPOF IV$$x0 000182424 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000182424 7001_ $$aMai, Elias K$$b1 000182424 7001_ $$aBertsch, Uta$$b2 000182424 7001_ $$aFenk, Roland$$b3 000182424 7001_ $$aNievergall, Eva$$b4 000182424 7001_ $$0P:(DE-He78)2ef631585610340ff425c9c31fcabd03$$aTichy, Diana$$b5$$udkfz 000182424 7001_ $$aBesemer, Britta$$b6 000182424 7001_ $$aDürig, Jan$$b7 000182424 7001_ $$aSchroers, Roland$$b8 000182424 7001_ $$avon Metzler, Ivana$$b9 000182424 7001_ $$aHänel, Mathias$$b10 000182424 7001_ $$aMann, Christoph$$b11 000182424 7001_ $$aAsemissen, Anne M$$b12 000182424 7001_ $$aHeilmeier, Bernhard$$b13 000182424 7001_ $$aWeinhold, Niels$$b14 000182424 7001_ $$aHuhn, Stefanie$$b15 000182424 7001_ $$aKriegsmann, Katharina$$b16 000182424 7001_ $$aLuntz, Steffen P$$b17 000182424 7001_ $$aHolderried, Tobias A W$$b18 000182424 7001_ $$aTrautmann-Grill, Karolin$$b19 000182424 7001_ $$aGezer, Deniz$$b20 000182424 7001_ $$aKlaiber-Hakimi, Maika$$b21 000182424 7001_ $$aMüller, Martin$$b22 000182424 7001_ $$aKhandanpour, Cyrus$$b23 000182424 7001_ $$aKnauf, Wolfgang$$b24 000182424 7001_ $$aScheid, Christof$$b25 000182424 7001_ $$aMunder, Markus$$b26 000182424 7001_ $$aGeer, Thomas$$b27 000182424 7001_ $$aRiesenberg, Hendrik$$b28 000182424 7001_ $$aThomalla, Jörg$$b29 000182424 7001_ $$aHoffmann, Martin$$b30 000182424 7001_ $$aRaab, Marc S$$b31 000182424 7001_ $$aSalwender, Hans J$$b32 000182424 7001_ $$aWeisel, Katja C$$b33 000182424 7001_ $$aGroup, German-Speaking Myeloma Multicenter$$b34$$eCollaboration Author 000182424 7001_ $$aAsemissen, Anne M$$b35$$eContributor 000182424 7001_ $$aBehringer, Joachim$$b36$$eContributor 000182424 7001_ $$aBernhard, Helga$$b37$$eContributor 000182424 7001_ $$aBernhardt, Christiane$$b38$$eContributor 000182424 7001_ $$aBertsch, Uta$$b39$$eContributor 000182424 7001_ $$aBesemer, Britta$$b40$$eContributor 000182424 7001_ $$aBlau, Igor W$$b41$$eContributor 000182424 7001_ $$aBolling, Claus$$b42$$eContributor 000182424 7001_ $$aDebatin, Daniel$$b43$$eContributor 000182424 7001_ $$aDingeldein, Gerrit$$b44$$eContributor 000182424 7001_ $$aDürig, Jan$$b45$$eContributor 000182424 7001_ $$aFenk, Roland$$b46$$eContributor 000182424 7001_ $$aFerstl, Barbara$$b47$$eContributor 000182424 7001_ $$aFest, Claudia$$b48$$eContributor 000182424 7001_ $$aFronhoffs, Stefan$$b49$$eContributor 000182424 7001_ $$aFuhrmann, Stephan$$b50$$eContributor 000182424 7001_ $$aGaska, Tobias$$b51$$eContributor 000182424 7001_ $$aGeer, Thomas$$b52$$eContributor 000182424 7001_ $$aGezer, Deniz$$b53$$eContributor 000182424 7001_ $$aGoldschmidt, Hartmut$$b54$$eContributor 000182424 7001_ $$aGörner, Martin$$b55$$eContributor 000182424 7001_ $$aGraeven, Ullrich$$b56$$eContributor 000182424 7001_ $$aGrassinger, Jochen$$b57$$eContributor 000182424 7001_ $$aHänel, Mathias$$b58$$eContributor 000182424 7001_ $$aHeilmeier, Bernhard$$b59$$eContributor 000182424 7001_ $$aHeinsch, Michael$$b60$$eContributor 000182424 7001_ $$aHeld, Gerhard$$b61$$eContributor 000182424 7001_ $$aHoffmann, Martin$$b62$$eContributor 000182424 7001_ $$aHolderried, Tobias A W$$b63$$eContributor 000182424 7001_ $$aHopfer, Olaf$$b64$$eContributor 000182424 7001_ $$aHuhn, Stefanie$$b65$$eContributor 000182424 7001_ $$aImmenschuh, Peter$$b66$$eContributor 000182424 7001_ $$aKaddu-Mulindwa, Dominic$$b67$$eContributor 000182424 7001_ $$aKhandanpour, Cyrus$$b68$$eContributor 000182424 7001_ $$aKlaiber-Hakimi, Maika$$b69$$eContributor 000182424 7001_ $$aKlausmann, Martine$$b70$$eContributor 000182424 7001_ $$aKlein, Stefan$$b71$$eContributor 000182424 7001_ $$aKnauf, Wolfgang$$b72$$eContributor 000182424 7001_ $$aKo, Yon-Dschun$$b73$$eContributor 000182424 7001_ $$aKöchling, Georg$$b74$$eContributor 000182424 7001_ $$aKoenigsmann, Michael$$b75$$eContributor 000182424 7001_ $$aKostrewa, Philippe$$b76$$eContributor 000182424 7001_ $$aKraemer, Doris Maria$$b77$$eContributor 000182424 7001_ $$aKremers, Stephan$$b78$$eContributor 000182424 7001_ $$aKriegsmann, Katharina$$b79$$eContributor 000182424 7001_ $$aKropff, Martin$$b80$$eContributor 000182424 7001_ $$aLa Rosée, Paul$$b81$$eContributor 000182424 7001_ $$aLuntz, Steffen P$$b82$$eContributor 000182424 7001_ $$aMahlberg, Rolf$$b83$$eContributor 000182424 7001_ $$aMai, Elias K$$b84$$eContributor 000182424 7001_ $$aMann, Christoph$$b85$$eContributor 000182424 7001_ $$aMartens, Uwe$$b86$$eContributor 000182424 7001_ $$avon Metzler, Ivana$$b87$$eContributor 000182424 7001_ $$aMüller, Martin$$b88$$eContributor 000182424 7001_ $$aMunder, Markus$$b89$$eContributor 000182424 7001_ $$aNeise, Michael$$b90$$eContributor 000182424 7001_ $$aNievergall, Eva$$b91$$eContributor 000182424 7001_ $$aNückel, Holger$$b92$$eContributor 000182424 7001_ $$aPönisch, Wolfram$$b93$$eContributor 000182424 7001_ $$aProcaccianti, Maria$$b94$$eContributor 000182424 7001_ $$aRaab, Marc S$$b95$$eContributor 000182424 7001_ $$aRafiyan, Mohammed R$$b96$$eContributor 000182424 7001_ $$aReimer, Peter$$b97$$eContributor 000182424 7001_ $$aRiecke, Armin$$b98$$eContributor 000182424 7001_ $$aRiesenberg, Hendrik$$b99$$eContributor 000182424 7001_ $$aRummel, Mathias$$b100$$eContributor 000182424 7001_ $$aRunde, Volker$$b101$$eContributor 000182424 7001_ $$aSalwender, Hans J$$b102$$eContributor 000182424 7001_ $$aSchaich, Markus$$b103$$eContributor 000182424 7001_ $$aScheid, Christoph$$b104$$eContributor 000182424 7001_ $$aSchmidt-Hieber, Martin$$b105$$eContributor 000182424 7001_ $$aSchmitt, Stefan$$b106$$eContributor 000182424 7001_ $$aSchöndube, Daniel$$b107$$eContributor 000182424 7001_ $$aSchroers, Roland$$b108$$eContributor 000182424 7001_ $$aSchwarzer, Andreas$$b109$$eContributor 000182424 7001_ $$aStaib, Peter$$b110$$eContributor 000182424 7001_ $$aSteiniger, Heike$$b111$$eContributor 000182424 7001_ $$aSturmberg, Dirk$$b112$$eContributor 000182424 7001_ $$aThomalla, Jörg$$b113$$eContributor 000182424 7001_ $$0P:(DE-He78)2ef631585610340ff425c9c31fcabd03$$aTichy, Diana$$b114$$eContributor$$udkfz 000182424 7001_ $$aTischler, Hans-Joachim$$b115$$eContributor 000182424 7001_ $$aTrautmann-Grill, Karolin$$b116$$eContributor 000182424 7001_ $$aTrummer, Arne$$b117$$eContributor 000182424 7001_ $$aTschechne, Barbara$$b118$$eContributor 000182424 7001_ $$aVerbeek, Walter$$b119$$eContributor 000182424 7001_ $$aWeinhold, Niels$$b120$$eContributor 000182424 7001_ $$aWeisel, Katja C$$b121$$eContributor 000182424 7001_ $$aWhitlock, Bettina$$b122$$eContributor 000182424 7001_ $$ade Wit, Maike$$b123$$eContributor 000182424 7001_ $$aZaiß, Matthias$$b124$$eContributor 000182424 7001_ $$aZiske, Carsten$$b125$$eContributor 000182424 773__ $$0PERI:(DE-600)2802056-X$$a10.1016/S2352-3026(22)00263-0$$gVol. 9, no. 11, p. e810 - e821$$n11$$pe810 - e821$$tThe lancet <London> / Haematology$$v9$$x2352-3026$$y2022 000182424 909CO $$ooai:inrepo02.dkfz.de:182424$$pVDB 000182424 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)2ef631585610340ff425c9c31fcabd03$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ 000182424 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)2ef631585610340ff425c9c31fcabd03$$aDeutsches Krebsforschungszentrum$$b114$$kDKFZ 000182424 9131_ $$0G:(DE-HGF)POF4-313$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vKrebsrisikofaktoren und Prävention$$x0 000182424 9141_ $$y2022 000182424 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-02-03 000182424 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-02-03 000182424 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bLANCET HAEMATOL : 2021$$d2022-11-19 000182424 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-19 000182424 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-19 000182424 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-19 000182424 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-19 000182424 915__ $$0StatID:(DE-HGF)9930$$2StatID$$aIF >= 30$$bLANCET HAEMATOL : 2021$$d2022-11-19 000182424 9201_ $$0I:(DE-He78)C060-20160331$$kC060$$lC060 Biostatistik$$x0 000182424 980__ $$ajournal 000182424 980__ $$aVDB 000182424 980__ $$aI:(DE-He78)C060-20160331 000182424 980__ $$aUNRESTRICTED