000096242 001__ 96242
000096242 005__ 20210902121633.0
000096242 0247_ $$2doi$$a10.1200/JCO.19.01231
000096242 0248_ $$2sideral$$a117214
000096242 037__ $$aART-2020-117214
000096242 041__ $$aeng
000096242 100__ $$aPaiva, B.
000096242 245__ $$aMeasurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma
000096242 260__ $$c2020
000096242 5060_ $$aAccess copy available to the general public$$fUnrestricted
000096242 5203_ $$aPURPOSE: Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG).
PATIENTS AND METHODS: In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with bortezomib, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1, 100 bone marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved by NGF was 2.9 × 10-6. Patients received maintenance (lenalidomide ± ixazomib) according to the companion PETHEMA/GEM2014MAIN trial.
RESULTS: Overall, 205 (45%) of 458 patients had undetectable MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetectable MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; P < .001) and an 88% reduction in the risk of death (hazard ratio, 0.12; 95% CI, 0.05 to 0.29; P < .001). Timing of undetectable MRD (after induction v intensification) had no impact on patient survival. Attaining undetectable MRD overcame poor prognostic features at diagnosis, including high-risk cytogenetics. By contrast, patients with Revised International Staging System III status and positive MRD had dismal progression-free and overall survivals (median, 14 and 17 months, respectively). Maintenance increased the rate of undetectable MRD by 17%.
CONCLUSION: The IMWG flow MRD-negative response criterion is highly applicable and sensitive to evaluate treatment efficacy in MM.
000096242 536__ $$9info:eu-repo/grantAgreement/EC/H2020/680200/EU/Integrated next-generation flow cytometry and sequencing to uncover the pathway of curability in multiple myeloma/MYELOMANEXT$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 680200-MYELOMANEXT$$9info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI15-01956$$9info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI15-02049$$9info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI15-02062$$9info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI18-01709$$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/ISCIII-CB16-12-00369$$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/ISCIII-CB16-12-00400$$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/ISCIII-CB16/12/00284
000096242 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000096242 590__ $$a44.544$$b2020
000096242 591__ $$aONCOLOGY$$b4 / 242 = 0.017$$c2020$$dQ1$$eT1
000096242 592__ $$a10.481$$b2020
000096242 593__ $$aCancer Research$$c2020$$dQ1
000096242 593__ $$aOncology$$c2020$$dQ1
000096242 593__ $$aMedicine (miscellaneous)$$c2020$$dQ1
000096242 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000096242 700__ $$aPuig, N.
000096242 700__ $$aCedena, M.T.
000096242 700__ $$aRosiñol, L.
000096242 700__ $$aCordón, L.
000096242 700__ $$aVidriales, M.B.
000096242 700__ $$aBurgos, L.
000096242 700__ $$aFlores-Montero, J.
000096242 700__ $$aSanoja-Flores, L.
000096242 700__ $$aLopez-Anglada, L.
000096242 700__ $$aMaldonado, R.
000096242 700__ $$ade la Cruz, J.
000096242 700__ $$aGutierrez, N.C.
000096242 700__ $$aCalasanz, M.J.
000096242 700__ $$aMartin-Ramos, M.L.
000096242 700__ $$aGarcia-Sanz, R.
000096242 700__ $$aMartinez-Lopez, J.
000096242 700__ $$aOriol, A.
000096242 700__ $$aBlanchard, M.J.
000096242 700__ $$aRios, R.
000096242 700__ $$aMartin, J.
000096242 700__ $$aMartinez-Martinez, R.
000096242 700__ $$aSureda, A.
000096242 700__ $$aHernandez, M.T.
000096242 700__ $$ade la Rubia, J.
000096242 700__ $$aKrsnik, I.
000096242 700__ $$aMoraleda, J.M.
000096242 700__ $$0(orcid)0000-0001-8515-3599$$aPalomera, L.$$uUniversidad de Zaragoza
000096242 700__ $$aBargay, J.
000096242 700__ $$aVan Dongen, J.J.M.
000096242 700__ $$aOrfao, A.
000096242 700__ $$aMateos, M.V.
000096242 700__ $$aBlade, J.
000096242 700__ $$aSan-Miguel, J.F.
000096242 700__ $$aLahuerta, J.J.
000096242 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000096242 773__ $$g38, 8 (2020), 784-792$$pJ. clin. oncol.$$tJOURNAL OF CLINICAL ONCOLOGY$$x0732-183X
000096242 8564_ $$s1375171$$uhttps://zaguan.unizar.es/record/96242/files/texto_completo.pdf$$yVersión publicada
000096242 8564_ $$s41542$$uhttps://zaguan.unizar.es/record/96242/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000096242 909CO $$ooai:zaguan.unizar.es:96242$$particulos$$pdriver
000096242 951__ $$a2021-09-02-08:54:49
000096242 980__ $$aARTICLE