{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T01:34:15Z","timestamp":1789263255497,"version":"build-2803163510"},"reference-count":96,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Immunotherapeutic targets in multiple myeloma (MM) have variable expression height and are partly expressed in subfractions of patients only. With increasing numbers of available compounds, strategies for appropriate choice of targets (combinations) are warranted. Simultaneously, risk assessment is advisable as patient\u2019s life expectancy varies between months and decades.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We first assess feasibility of RNA-sequencing in a multicenter trial (GMMG-MM5, n=604 patients). Next, we use a clinical routine cohort of untreated symptomatic myeloma patients undergoing autologous stem cell transplantation (n=535, median follow-up (FU) 64 months) to perform RNA-sequencing, gene expression profiling (GEP), and iFISH by ten-probe panel on CD138-purified malignant plasma cells. We subsequently compare target expression to plasma cell precursors, MGUS (n=59), asymptomatic (n=142) and relapsed (n=69) myeloma patients, myeloma cell lines (n=26), and between longitudinal samples (MM vs. relapsed MM). Data are validated using the independent MMRF CoMMpass-cohort (n=767, FU 31 months).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RNA-sequencing is feasible in 90.8% of patients (GMMG-MM5). Actionable immune-oncological targets (n=19) can be divided in those expressed in all normal and &amp;gt;99% of MM-patients (CD38, SLAMF7, BCMA, GPRC5D, FCRH5, TACI, CD74, CD44, CD37, CD79B), those with expression loss in subfractions of MM-patients (BAFF-R [81.3%], CD19 [57.9%], CD20 [82.8%], CD22 [28.4%]), aberrantly expressed in MM (NY-ESO1\/2 [12%], MUC1 [12.7%], CD30 [4.9%], mutated BRAF V600E\/K [2.1%]), and resistance-conveying target-mutations e.g., against part but not all BCMA-directed treatments. Risk is assessable regarding proliferation, translated GEP- (UAMS70-, SKY92-, RS-score) and <jats:italic>de novo<\/jats:italic> (LfM-HRS) defined risk scores. LfM-HRS delineates three groups of 40%, 38%, and 22% of patients with 5-year and 12-year survival rates of 84% (49%), 67% (18%), and 32% (0%). R-ISS and RNA-sequencing identify partially overlapping patient populations, with R-ISS missing, e.g., 30% (22\/72) of highly proliferative myeloma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>RNA-sequencing based assessment of risk and targets for first choice treatment is possible in clinical routine.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1286700","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T09:28:30Z","timestamp":1700040510000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["RNA-sequencing based first choice of treatment and determination of risk in multiple myeloma"],"prefix":"10.3389","volume":"14","author":[{"given":"Martina","family":"Emde-Rajaratnam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Benes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Salwender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Bertsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Scheid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"H\u00e4nel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Weisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hielscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Raab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Goldschmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Jauch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Maes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"De Bruyne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"Menu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"De Veirman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Moreaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Vanderkerken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Seckinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Hose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041875","article-title":"Multiple myeloma","volume":"351","author":"Kyle","year":"2004","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","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":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00128-5","article-title":"Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial","volume":"22","author":"Dimopoulos","year":"2021","journal-title":"Lancet Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00592-4","article-title":"Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial","volume":"397","author":"Moreau","year":"2021","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805762","article-title":"Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma","volume":"379","author":"Dimopoulos","year":"2018","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204591","article-title":"Talquetamab, a T-Cell\u2013redirecting GPRC5D bispecific antibody for multiple myeloma","volume":"387","author":"Chari","year":"2022","journal-title":"New Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30788-0","article-title":"Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study","volume":"21","author":"Lonial","year":"2020","journal-title":"Lancet Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024850","article-title":"Idecabtagene vicleucel in relapsed and refractory multiple myeloma","volume":"384","author":"Munshi","year":"2021","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00933-8","article-title":"Ciltacabtagene autoleucel, a b-cell maturation antigen-directed chimeric antigen receptor t-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b\/2 open-label study","volume":"398","author":"Berdeja","year":"2021","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01338-6","article-title":"Teclistamab, a b-cell maturation antigen x CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study","volume":"398","author":"Usmani","year":"2021","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02589-w","article-title":"Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial","volume":"29","author":"Bahlis","year":"2023","journal-title":"Nat Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30756-7","article-title":"Treatment of relapsed and refractory multiple myeloma: recommendations from the international myeloma working group","volume":"22","author":"Moreau","year":"2021","journal-title":"Lancet Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.11.014","article-title":"Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up(dagger)","volume":"32","author":"Dimopoulos","year":"2021","journal-title":"Ann Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030288","article-title":"A phase 2 study of bortezomib in relapsed, refractory myeloma","volume":"348","author":"Richardson","year":"2003","journal-title":"New Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-0822","article-title":"A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies","volume":"15","author":"O'Connor","year":"2009","journal-title":"Clin Cancer Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2015.60","article-title":"Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib","volume":"5","author":"Kumar","year":"2015","journal-title":"Blood Cancer J"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199911183412102","article-title":"Antitumor activity of thalidomide in refractory multiple myeloma","volume":"341","author":"Singhal","year":"1999","journal-title":"N Engl J Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0996","article-title":"Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma","volume":"100","author":"Richardson","year":"2002","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70380-2","article-title":"Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial","volume":"14","author":"Miguel","year":"2013","journal-title":"Lancet Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.10.052","article-title":"Phase i study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma","volume":"22","author":"Schey","year":"2004","journal-title":"J Clin Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005288","article-title":"Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial","volume":"136","author":"Voorhees","year":"2020","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.140","article-title":"Gene expression profile alone is inadequate in predicting complete response in multiple myeloma","volume":"28","author":"Amin","year":"2014","journal-title":"Leukemia"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0867","article-title":"Gene expression profiles in myeloma: Ready for the real world","volume":"22","author":"Szalat","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-013-1757-6","article-title":"Correlation between eight-gene expression profiling and response to therapy of newly diagnosed multiple myeloma patients treated with thalidomide-dexamethasone incorporated into double autologous transplantation","volume":"92","author":"Terragna","year":"2013","journal-title":"Ann Hematol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005532","article-title":"MCT1 is a predictive marker for lenalidomide maintenance therapy in multiple myeloma","volume":"6","author":"Stroh","year":"2022","journal-title":"Blood Adv"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-788786","article-title":"Efficacy of venetoclax as targeted therapy for relapsed\/refractory t(11;14) multiple myeloma","volume":"130","author":"Kumar","year":"2017","journal-title":"Blood"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-788323","article-title":"Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed\/refractory MM","volume":"130","author":"Moreau","year":"2017","journal-title":"Blood"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007899","article-title":"Venetoclax sensitivity in multiple myeloma is associated with b-cell gene expression","volume":"137","author":"Gupta","year":"2021","journal-title":"Blood"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0014","article-title":"Targeting the BRAF V600E mutation in multiple myeloma","volume":"3","author":"Andrulis","year":"2013","journal-title":"Cancer Discovery"},{"key":"B30","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/s13045-023-01479-5","article-title":"BCMA-targeted CAR-t cell therapies in relapsed and\/or refractory multiple myeloma: latest updates from 2023 ASCO annual meeting","volume":"16","author":"Wu","year":"2023","journal-title":"J Hematol Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-133873","article-title":"A phase 1, first-in-Human study of talquetamab, a g protein-coupled receptor family c group 5 member d (GPRC5D) x CD3 bispecific antibody, in patients with relapsed and\/or refractory multiple myeloma (RRMM)","volume":"136","author":"Chari","year":"2020","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-146868","article-title":"Updated phase 1 results from MonumenTAL-1: First-in-Human study of talquetamab, a g protein-coupled receptor family c group 5 member d x CD3 bispecific antibody, in patients with Relapsed\/Refractory multiple myeloma","volume":"138","author":"Krishnan","year":"2021","journal-title":"Blood"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-153204","article-title":"Phase i first-in-Class trial of MCARH109, a g protein coupled receptor class c group 5 member d (GPRC5D) targeted CAR t cell therapy in patients with relapsed or refractory multiple myeloma","volume":"138","author":"Mailankody","year":"2021","journal-title":"Blood"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-136985","article-title":"Initial clinical activity and safety of BFCR4350A, a FcRH5\/CD3 t-Cell-Engaging bispecific antibody, in Relapsed\/Refractory multiple myeloma","volume":"136","author":"Cohen","year":"2020","journal-title":"Blood"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-147983","article-title":"Cevostamab monotherapy continues to show clinically meaningful activity and manageable safety in patients with heavily pre-treated Relapsed\/Refractory multiple myeloma (RRMM): Updated results from an ongoing phase i study","volume":"138","author":"Trudel","year":"2021","journal-title":"Blood"},{"key":"B36","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s13045-023-01489-3","article-title":"Bispecific antibodies targeting BCMA, GPRC5D, and FcRH5 for multiple myeloma therapy: latest updates from ASCO 2023 annual meeting","volume":"16","author":"Zhao","year":"2023","journal-title":"J Hematol Oncol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"Jco2300512","DOI":"10.1200\/JCO.23.00512","article-title":"Chimeric antigen receptor t-cell and bispecific antibody therapy in multiple myeloma: Moving into the future","volume":"2023","author":"Holstein","year":"2023","journal-title":"J Clin Oncol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s13045-023-01482-w","article-title":"Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies","volume":"16","author":"Tapia-Galisteo","year":"2023","journal-title":"J Hematol Oncol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01676","article-title":"CD38 as immunotherapeutic target in light chain amyloidosis and multiple myeloma-association with molecular entities, risk, survival, and mechanisms of upfront resistance","volume":"9","author":"Seckinger","year":"2018","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018023200","article-title":"Cytogenetic intraclonal heterogeneity of plasma cell dyscrasia in AL amyloidosis as compared with multiple myeloma","volume":"2","author":"Bochtler","year":"2018","journal-title":"Blood Adv"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003805","article-title":"Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma","volume":"5","author":"Verkleij","year":"2021","journal-title":"Blood Advances"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11215","article-title":"Frequency of expression and generation of t-cell responses against antigens on multiple myeloma cells in patients included in the GMMG-MM5 trial","volume":"8","author":"Schmitt","year":"2017","journal-title":"Oncotarget"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-703439","article-title":"CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma","volume":"128","author":"Nijhof","year":"2016","journal-title":"Blood"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00246-2","article-title":"Gamma-secretase inhibitor in combination with BCMA chimeric antigen receptor t-cell immunotherapy for individuals with relapsed or refractory multiple myeloma: a phase 1, first-in-human trial","volume":"24","author":"Cowan","year":"2023","journal-title":"Lancet Oncol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02491-5","article-title":"Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma","volume":"29","author":"Lee","year":"2023","journal-title":"Nat Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.2267","article-title":"Revised international staging system for multiple myeloma: A report from international myeloma working group","volume":"33","author":"Palumbo","year":"2015","journal-title":"J Clin Oncol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3324\/haematol.2010.030296","article-title":"Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma","volume":"96","author":"Hose","year":"2011","journal-title":"Haematologica"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-038430","article-title":"A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1","volume":"109","author":"Shaughnessy","year":"2007","journal-title":"Blood"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.13.8545","article-title":"Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the intergroupe francophone du myelome","volume":"26","author":"Decaux","year":"2008","journal-title":"J Clin Oncol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt124","article-title":"Modeling risk stratification in human cancer","volume":"29","author":"Reme","year":"2013","journal-title":"Bioinformatics"},{"key":"B51","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s13045-019-0750-5","article-title":"Prospective target assessment and multimodal prediction of survival for personalized and risk-adapted treatment strategies in multiple myeloma in the GMMG-MM5 multicenter trial","volume":"12","author":"Hose","year":"2019","journal-title":"J Hematol Oncol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.127","article-title":"A gene expression signature for high-risk multiple myeloma","volume":"26","author":"Kuiper","year":"2012","journal-title":"Leukemia"},{"key":"B53","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/978-1-4939-7865-6_7","article-title":"RNA-sequencing from low-input material in multiple myeloma for application in clinical routine","volume":"1792","author":"Seckinger","year":"2018","journal-title":"Methods Mol Biol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0724-1","article-title":"Response-adapted lenalidomide maintenance in newly diagnosed myeloma: results from the phase III GMMG-MM5 trial","volume":"34","author":"Goldschmidt","year":"2020","journal-title":"Leukemia"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-235960","article-title":"An in vitro model of differentiation of memory b cells into plasmablasts and plasma cells including detailed phenotypic and molecular characterization","volume":"114","author":"Jourdan","year":"2009","journal-title":"Blood"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-184226","article-title":"Induction of angiogenesis by normal and malignant plasma cells","volume":"114","author":"Hose","year":"2009","journal-title":"Blood"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-178350","article-title":"Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myeloma","volume":"113","author":"Hose","year":"2009","journal-title":"Blood"},{"key":"B58","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.ccell.2017.02.002","article-title":"Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-t cell bispecific antibody EM801 for multiple myeloma treatment","volume":"31","author":"Seckinger","year":"2017","journal-title":"Cancer Cell"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.257","article-title":"Bone morphogenic protein 6: a member of a novel class of prognostic factors expressed by normal and malignant plasma cells inhibiting proliferation and angiogenesis","volume":"28","author":"Seckinger","year":"2009","journal-title":"Oncogene"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.4923","article-title":"Progression in smoldering myeloma is independently determined by the chromosomal abnormalities del(17p), t(4;14), gain 1q, hyperdiploidy, and tumor load","volume":"31","author":"Neben","year":"2013","journal-title":"J Clin Oncol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1080\/03610928408828837","article-title":"Nonparametric estimation of the survival distribution in censored data","volume":"13","author":"Fleming","year":"1984","journal-title":"Comm Stat Theory Methods"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1958.10501452","article-title":"Nonparametric estimation from incomplete observations","volume":"53","author":"Kaplan","year":"1958","journal-title":"J Am Stat Assoc"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/69.3.553","article-title":"A class of rank test procedures for censored survival data","volume":"69","author":"Harrington","year":"1982","journal-title":"Biometrika"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/9.5.791","article-title":"Cytotoxic t lymphocytes derived from bone marrow mononuclear cells of multiple myeloma patients recognize an underglycosylated form of MUC1 mucin","volume":"9","author":"Noto","year":"1997","journal-title":"Int Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V72.1.219.219","article-title":"Value of beta 2-microglobulin level and plasma cell labeling indices as prognostic factors in patients with newly diagnosed myeloma","volume":"72","author":"Greipp","year":"1988","journal-title":"Blood"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.12.3382.3382","article-title":"Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and c-reactive protein in multiple myeloma","volume":"81","author":"Greipp","year":"1993","journal-title":"Blood"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.2.448.448","article-title":"A new staging system for multiple myeloma based on the number of s-phase plasma cells","volume":"85","author":"San Miguel","year":"1995","journal-title":"Blood"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1984.tb06116.x","article-title":"Low plasma cell 3(H) thymidine incorporation in monoclonal gammopathy of undetermined significance (MGUS), smouldering myeloma and remission phase myeloma: a reliable indicator of patients not requiring therapy","volume":"58","author":"Boccadoro","year":"1984","journal-title":"Br J Haematol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0750-z","article-title":"Predicting ultrahigh risk multiple myeloma by molecular profiling: an analysis of newly diagnosed transplant eligible myeloma XI trial patients","volume":"34","author":"Shah","year":"2020","journal-title":"Leukemia"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.179","article-title":"Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles of 1905 trial patients","volume":"32","author":"Shah","year":"2018","journal-title":"Leukemia"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-09-044974","article-title":"Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib","volume":"109","author":"Mulligan","year":"2007","journal-title":"Blood"},{"key":"B72","doi-asserted-by":"publisher","first-page":"e046225","DOI":"10.1136\/bmjopen-2020-046225","article-title":"MUKnine OPTIMUM protocol: a screening study to identify high-risk patients with multiple myeloma suitable for novel treatment approaches combined with a phase II study evaluating optimised combination of biological therapy in newly diagnosed high-risk multiple myeloma and plasma cell leukaemia","volume":"11","author":"Brown","year":"2021","journal-title":"BMJ Open"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14213","article-title":"Multiple myeloma: patient outcomes in real-world practice","volume":"175","author":"Yong","year":"2016","journal-title":"Br J Haematol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2209900","article-title":"GPRC5D-targeted CAR t cells for myeloma","volume":"387","author":"Mailankody","year":"2022","journal-title":"N Engl J Med"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004418","article-title":"Single- and double-hit events in genes encoding immune targets before and after t cell-engaging antibody therapy in MM","volume":"5","author":"Truger","year":"2021","journal-title":"Blood Adv"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-405985","article-title":"Clonal competition with alternating dominance in multiple myeloma","volume":"120","author":"Keats","year":"2012","journal-title":"Blood"},{"key":"B77","doi-asserted-by":"publisher","first-page":"4517","DOI":"10.1038\/s41467-022-32145-y","article-title":"The spatio-temporal evolution of multiple myeloma from baseline to relapse-refractory states","volume":"13","author":"Rasche","year":"2022","journal-title":"Nat Commun"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.5.1745","article-title":"Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells","volume":"99","author":"Zhan","year":"2002","journal-title":"Blood"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1038\/nature09837","article-title":"Initial genome sequencing and analysis of multiple myeloma","volume":"471","author":"Chapman","year":"2011","journal-title":"Nature"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00189","article-title":"Next-generation sequencing for clinical management of multiple myeloma: Ready for prime time","volume":"10","author":"Bolli","year":"2020","journal-title":"Front Oncol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2017.1332996","article-title":"Utilizing next-generation sequencing in the management of multiple myeloma","volume":"17","author":"Lionetti","year":"2017","journal-title":"Expert Rev Mol Diagn"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-1628","article-title":"Gene expression profiling in multiple myeloma\u2013reporting of entities, risk, and targets in clinical routine","volume":"17","author":"Meissner","year":"2011","journal-title":"Clin Cancer Res"},{"key":"B83","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1755-8794-7-25","article-title":"Translating a gene expression signature for multiple myeloma prognosis into a robust high-throughput assay for clinical use","volume":"7","author":"van Laar","year":"2014","journal-title":"BMC Med Genomics"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2019.01.003","article-title":"Next generation sequencing-based validation of the revised international staging system for multiple myeloma: An analysis of the MMRF CoMMpass study","volume":"19","author":"Goldsmith","year":"2019","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"B85","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cancergen.2020.01.001","article-title":"The combination of WGS and RNA-seq is superior to conventional diagnostic tests in multiple myeloma: Ready for prime time","volume":"242","author":"Hollein","year":"2020","journal-title":"Cancer Genet"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1002\/jha2.276","article-title":"Validation of clinical-grade whole genome sequencing reproduces cytogenetic analysis and identifies mutational landscape in newly-diagnosed multiple myeloma patients: A pilot study from the 100,000 genomes project","volume":"2","author":"Lomas","year":"2021","journal-title":"EJHaem"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2021.1964021","article-title":"Whole genome sequencing demonstrates substantial pathophysiological differences of MYC rearrangements in patients with plasma cell myeloma and b-cell lymphoma","volume":"62","author":"Bendig","year":"2021","journal-title":"Leuk Lymphoma"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16744","article-title":"Development of an RNA sequencing-based prognostic gene signature in multiple myeloma","volume":"192","author":"Zamani-Ahmadmahmudi","year":"2021","journal-title":"Br J Haematol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"6997","DOI":"10.1038\/ncomms7997","article-title":"APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma","volume":"6","author":"Walker","year":"2015","journal-title":"Nat Commun"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.345","article-title":"Biological and prognostic impact of APOBEC-induced mutations in the spectrum of plasma cell dyscrasias and multiple myeloma cell lines","volume":"32","author":"Maura","year":"2018","journal-title":"Leukemia"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016212","article-title":"The location of the t(4;14) translocation breakpoint within the NSD2 gene identifies a subset of patients with high-risk NDMM","volume":"141","author":"Stong","year":"2023","journal-title":"Blood"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2013.01.019","article-title":"Management of newly diagnosed symptomatic multiple myeloma: updated mayo stratification of myeloma and risk-adapted therapy (mSMART) consensus guidelines 2013","volume":"88","author":"Mikhael","year":"2013","journal-title":"Mayo Clin Proc"},{"key":"B93","doi-asserted-by":"publisher","first-page":"e453","DOI":"10.1038\/bcj.2016.64","article-title":"Dose-dense and less dose-intense total therapy 5 for gene expression profiling-defined high-risk multiple myeloma","volume":"6","author":"Jethava","year":"2016","journal-title":"Blood Cancer J"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-170464","article-title":"The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor","volume":"113","author":"Sprynski","year":"2009","journal-title":"Blood"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-09-825331","article-title":"Toward personalized treatment in multiple myeloma based on molecular characteristics","volume":"133","author":"Pawlyn","year":"2019","journal-title":"Blood"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-023-05196-x","article-title":"Early clinical trial unit tumor board: a real-world experience in a national cancer network","volume":"149","author":"Weiss","year":"2023","journal-title":"J Cancer Res Clin Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1286700\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T09:28:34Z","timestamp":1700040514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1286700\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,15]]},"references-count":96,"alternative-id":["10.3389\/fimmu.2023.1286700"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1286700","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,15]]},"article-number":"1286700"}}