{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T23:52:18Z","timestamp":1778543538608,"version":"3.51.4"},"reference-count":70,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Novel treatments are needed to address the lack of options for patients with relapsed or refractory multiple myeloma. Even though immunotherapy-based treatments have revolutionized the field in recent years, offering new opportunities for patients, there is still no curative therapy. Thus, non-immunologic agents, which have proven effective for decades, are still central to the treatment of multiple myeloma, especially for advanced disease. Building on their efficacy in myeloma, the development of proteasome inhibitors and immunomodulatory drugs has been pursued, and has led to the emergence of a novel generation of agents (e.g., carfilzomib, ixazomib, pomalidomide). The use of alkylating agents is decreasing in most treatment regimens, but melflufen, a peptide-conjugated alkylator with a completely new mechanism of action, offers interesting opportunities. Moreover, with the identification of novel targets, new drug classes have entered the myeloma armamentarium, such as XPO1 inhibitors (selinexor), HDAC inhibitors (panobinostat), and anti-BCL-2 agents (venetoclax). New pathways are still being explored, especially the possibility of a mutation-driven strategy, as biomarkers and targeted treatments are increasing. Though multiple myeloma is still considered incurable, the treatment options are expanding and are progressively becoming more diverse, largely because of the continuous development of non-immunologic agents.<\/jats:p>","DOI":"10.3390\/cancers13205210","type":"journal-article","created":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T16:43:55Z","timestamp":1634575435000},"page":"5210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel Non-Immunologic Agents for Relapsed and Refractory Multiple Myeloma: A Review Article"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8416-391X","authenticated-orcid":false,"given":"Arthur","family":"Bobin","sequence":"first","affiliation":[{"name":"Department of Hematology, CIC 1402, University Hospital, 86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9cile","family":"Gruchet","sequence":"additional","affiliation":[{"name":"Department of Hematology, CIC 1402, University Hospital, 86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phanie","family":"Guidez","sequence":"additional","affiliation":[{"name":"Department of Hematology, CIC 1402, University Hospital, 86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Gardeney","sequence":"additional","affiliation":[{"name":"Department of Hematology, CIC 1402, University Hospital, 86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laly","family":"Nsiala Makunza","sequence":"additional","affiliation":[{"name":"Department of Hematology, CIC 1402, University Hospital, 86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathilde","family":"Vonfeld","sequence":"additional","affiliation":[{"name":"Department of Hematology, CIC 1402, University Hospital, 86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"L\u00e9vy","sequence":"additional","affiliation":[{"name":"Department of Hematology, CIC 1402, University Hospital, 86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Cailly","sequence":"additional","affiliation":[{"name":"Department of Hematology, CIC 1402, University Hospital, 86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florence","family":"Sabirou","sequence":"additional","affiliation":[{"name":"Department of Hematology, CIC 1402, University Hospital, 86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Systchenko","sequence":"additional","affiliation":[{"name":"Department of Hematology, CIC 1402, University Hospital, 86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels","family":"Moya","sequence":"additional","affiliation":[{"name":"Department of Hematology, CIC 1402, University Hospital, 86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Leleu","sequence":"additional","affiliation":[{"name":"Department of Hematology, CIC 1402, University Hospital, 86000 Poitiers, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"867","DOI":"10.4065\/79.7.867","article-title":"Clinical course of patients with relapsed multiple myeloma","volume":"79","author":"Kumar","year":"2004","journal-title":"Mayo Clin. Proc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1182\/blood-2019-123483","article-title":"Four-Year Follow-up of the Phase 3 Pollux Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Relapsed or Refractory Multiple Myeloma (RRMM)","volume":"134","author":"Kaufman","year":"2019","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1182\/blood-2019-123426","article-title":"Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Ineligible for Transplant: Updated Analysis of Maia","volume":"134","author":"Bahlis","year":"2019","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(19)31240-1","article-title":"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","volume":"394","author":"Moreau","year":"2019","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7498","DOI":"10.1158\/1078-0432.CCR-17-2027","article-title":"Monocytes and granulocytes reduce CD38 expression levels on myeloma cells in patients treated with daratumumab","volume":"23","author":"Krejcik","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1182\/blood-2016-03-703439","article-title":"CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma","volume":"28","author":"Nijhof","year":"2016","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/fragi.2020.602108","article-title":"Aging of the Immune System: Research Challenges to Enhance the Health Span of Older Adults","volume":"1","author":"Haynes","year":"2020","journal-title":"Front. Aging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1182\/blood-2019-121731","article-title":"Results from CARTITUDE-1: A Phase 1b\/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and\/or Refractory Multiple Myeloma (R\/R MM)","volume":"134","author":"Madduri","year":"2019","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8503","DOI":"10.1200\/JCO.2020.38.15_suppl.8503","article-title":"Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results","volume":"15","author":"Munshi","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/S0140-6736(21)01338-6","article-title":"Teclistamab, a B-cell maturation antigen\u2008\u00d7\u2008CD3 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":"ref_11","doi-asserted-by":"crossref","unstructured":"Mogoll\u00f3n, P., D\u00edaz-Tejedor, A., Algar\u00edn, E.M., Pa\u00edno, T., Garayoa, M., and Ocio, E.M. (2019). Biological Background of Resistance to Current Standards of Care in Multiple Myeloma. Cells, 8.","DOI":"10.3390\/cells8111432"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41408-021-00478-4","article-title":"A phase 2 study of isatuximab monotherapy in patients with multiple myeloma who are refractory to daratumumab","volume":"11","author":"Mikhael","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S1470-2045(15)00464-7","article-title":"Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study","volume":"17","author":"Dimopoulos","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1056\/NEJMoa1411321","article-title":"ASPIRE Carfilzomib, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma\u2014PROTOCOL","volume":"372","author":"Stewart","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S1470-2045(19)30152-4","article-title":"Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): A randomised, open-label, phase 3 trial","volume":"20","author":"Richardson","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.2217\/fon-2017-0616","article-title":"Isatuximab plus pomalidomide\/dexamethasone versus pomalidomide\/dexamethasone in relapsed\/refractory multiple myeloma: ICARIA Phase III study design","volume":"14","author":"Richardson","year":"2018","journal-title":"Future Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/S1470-2045(18)30354-1","article-title":"Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): Interim analysis results of a randomised, phase 3 study","volume":"19","author":"Moreau","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1056\/NEJMoa1516282","article-title":"Oral Ixazomib, lenalidomide, and dexamethasone for multiple myeloma","volume":"374","author":"Moreau","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4907","DOI":"10.1158\/1078-0432.CCR-18-3728","article-title":"A phase Ib\/II study of oprozomib in patients with advanced multiple myeloma and Waldenstrom \u20ac macroglobulinemia","volume":"25","author":"Ghobrial","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4559","DOI":"10.1158\/1078-0432.CCR-15-2616","article-title":"Phase i clinical trial of marizomib (NPI-0052) in patients with advanced malignancies including multiple myeloma: Study NPI-0052-102 final results","volume":"22","author":"Harrison","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1126\/science.1244851","article-title":"Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells","volume":"343","author":"Udeshi","year":"2014","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1126\/science.1244917","article-title":"The myeloma drug lenalidomide promotes the cereblon-dependent destruction of ikaros proteins","volume":"343","author":"Lu","year":"2014","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1055","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":"ref_24","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/s41375-019-0620-8","article-title":"Iberdomide (CC-220) is a potent cereblon E3 ligase modulator with antitumor and immunostimulatory activities in lenalidomide- and pomalidomide-resistant multiple myeloma cells with dysregulated CRBN","volume":"34","author":"Bjorklund","year":"2020","journal-title":"Leukemia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8006","DOI":"10.1200\/JCO.2019.37.15_suppl.8006","article-title":"First clinical (phase 1b\/2a) study of iberdomide (CC-220; IBER), a CELMoD, in combination with dexamethasone (DEX) in patients (pts) with relapsed\/refractory multiple myeloma (RRMM)","volume":"37","author":"Lonial","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8500","DOI":"10.1200\/JCO.2020.38.15_suppl.8500","article-title":"First-in-human phase I study of the novel CELMoD agent CC-92480 combined with dexamethasone (DEX) in patients (pts) with relapsed\/refractory multiple myeloma (RRMM)","volume":"38","author":"Richardson","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/j.1349-7006.2010.01826.x","article-title":"Aminopeptidase N (CD13) as a target for cancer chemotherapy","volume":"102","author":"Larsson","year":"2011","journal-title":"Cancer Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1158\/1078-0432.CCR-12-3752","article-title":"In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells","volume":"19","author":"Chauhan","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s10637-007-9092-1","article-title":"The novel alkylating prodrug J1: Diagnosis directed activity profile ex vivo and combination analyses in vitro","volume":"26","author":"Haglund","year":"2008","journal-title":"Investig. New Drugs"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1200\/JCO.20.02259","article-title":"Melflufen and dexamethasone in heavily pretreated relapsed and refractory multiple myeloma","volume":"39","author":"Richardson","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_31","first-page":"37","article-title":"ANCHOR (OP-104): Melflufen Plus Dexamethasone (dex) and Daratumumab (dara) or Bortezomib (BTZ) in Relapsed\/Refractory Multiple Myeloma (RRMM) Refractory to an IMiD and\/or a Proteasome Inhibitor (PI)\u2014Updated Efficacy and Safety","volume":"128","author":"Ocio","year":"2020","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrc2297","article-title":"Diagnosing and exploiting cancer\u2019s addiction to blocks in apoptosis","volume":"8","author":"Letai","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/sj.leu.2403784","article-title":"Mcl-1 is overexpressed in multiple myeloma and associated with relapse and shorter survival","volume":"19","author":"Robillard","year":"2005","journal-title":"Leukemia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1182\/blood-2010-11-317438","article-title":"ABT-737 is highly effective against molecular subgroups of multiple myeloma","volume":"118","author":"Bodet","year":"2011","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1182\/blood.2019002841","article-title":"How I manage CLL with venetoclax-based treatments","volume":"135","author":"Wierda","year":"2020","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1056\/NEJMoa2012971","article-title":"Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia","volume":"383","author":"DiNardo","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E31","DOI":"10.1016\/j.clml.2019.09.046","article-title":"A Phase 3 Study of Venetoclax or Placebo in Combination with Bortezomib and Dexamethasone in Patients with Relapsed\/Refractory Multiple Myeloma","volume":"19","author":"Kumar","year":"2019","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e116","DOI":"10.3324\/haematol.2018.212308","article-title":"Preclinical evaluation of the simultaneous inhibition of MCL-1 and BCL-2 with the combination of S63845 and venetoclax in multiple myeloma","volume":"105","author":"Corchete","year":"2020","journal-title":"Haematologica"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4166","DOI":"10.1182\/blood-2012-08-447581","article-title":"Prognostic impact and targeting of CRM1 in acute myeloid leukemia","volume":"121","author":"Kojima","year":"2013","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1002\/cncr.23354","article-title":"Expression of the nuclear export protein chromosomal region maintenance\/exportin 1\/Xpo1 is a prognostic factor in human ovarian cancer","volume":"112","author":"Noske","year":"2008","journal-title":"Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1038\/leu.2013.172","article-title":"Genome-wide studies in multiple myeloma identify XPO1\/CRM1 as a critical target validated using the selective nuclear export inhibitor KPT-276","volume":"27","author":"Schmidt","year":"2013","journal-title":"Leukemia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2040620720930629","DOI":"10.1177\/2040620720930629","article-title":"Selinexor in relapsed\/refractory multiple myeloma","volume":"11","author":"Richter","year":"2020","journal-title":"Ther. Adv. Hematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa1903455","article-title":"Oral Selinexor\u2013Dexamethasone for Triple-Class Refractory Multiple Myeloma","volume":"381","author":"Chari","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/S0140-6736(20)32292-3","article-title":"Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): A randomised, open-label, phase 3 trial","volume":"396","author":"Grosicki","year":"2020","journal-title":"Lancet"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8530","DOI":"10.1200\/JCO.2020.38.15_suppl.8530","article-title":"Once weekly selinexor, carfilzomib, and dexamethasone (SKd) in patients with relapsed\/refractory multiple myeloma (MM)","volume":"38","author":"Gasparetto","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8018","DOI":"10.1200\/JCO.2021.39.15_suppl.8018","article-title":"Oral selinexor, pomalidomide, and dexamethasone (XPd) at recommended phase 2 dose in relapsed refractory multiple myeloma (MM)","volume":"39","author":"White","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1038\/s41375-020-0756-6","article-title":"Integrated safety profile of selinexor in multiple myeloma: Experience from 437 patients enrolled in clinical trials","volume":"34","author":"Gavriatopoulou","year":"2020","journal-title":"Leukemia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"529","DOI":"10.2147\/JBM.S317966","article-title":"Profile and management of toxicity of selinexor and belantamab mafodotin for the treatment of triple class refractory multiple myeloma","volume":"12","author":"Neupane","year":"2021","journal-title":"J. Blood Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4509","DOI":"10.1182\/blood.V128.22.4509.4509","article-title":"A Phase 1\/2 Study of the Second Generation Selective Inhibitor of Nuclear Export (SINE) Compound, KPT-8602, in Patients with Relapsed Refractory Multiple Myeloma","volume":"128","author":"Cornell","year":"2016","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nrd2133","article-title":"Anticancer activities of histone deacetylase inhibitors","volume":"5","author":"Bolden","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1172\/JCI69738","article-title":"New and emerging HDAC inhibitors for cancer treatment","volume":"124","author":"West","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.3109\/10428194.2012.661175","article-title":"Phase II trial of the pan-deacetylase inhibitor panobinostat as a single agent in advanced relapsed\/refractory multiple myeloma","volume":"53","author":"Wolf","year":"2012","journal-title":"Leuk. Lymphoma"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"794","DOI":"10.3324\/haematol.2009.015495","article-title":"In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma","volume":"95","author":"Ocio","year":"2010","journal-title":"Haematologica"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1158\/1535-7163.MCT-11-0433","article-title":"Mechanism of action of proteasome inhibitors and deacetylase inhibitors and the biological basis of synergy in multiple myeloma","volume":"10","author":"Hideshima","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/S1470-2045(14)70440-1","article-title":"Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: A multicentre, randomised, double-blind phase 3 trial","volume":"15","author":"Hungria","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S1470-2045(20)30680-X","article-title":"Efficacy and safety of oral panobinostat plus subcutaneous bortezomib and oral dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma (PANORAMA 3): An open-label, randomised, phase 2 study","volume":"22","author":"Laubach","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_57","first-page":"428","article-title":"Phase I\/II study of the combination of panobinostat and carfilzomib in patients with relapsed\/refractory multiple myeloma","volume":"96","author":"Berdeja","year":"2015","journal-title":"Haematologica"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41408-018-0154-8","article-title":"Combining carfilzomib and panobinostat to treat relapsed\/refractory multiple myeloma: Results of a Multiple Myeloma Research Consortium Phase I Study","volume":"9","author":"Kaufman","year":"2019","journal-title":"Blood Cancer J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1182\/bloodadvances.2017007427","article-title":"A phase 2 study of panobinostat with lenalidomide and weekly dexamethasone in myeloma","volume":"1","author":"Chari","year":"2017","journal-title":"Blood Adv."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e572","DOI":"10.1016\/S2352-3026(16)30165-X","article-title":"Bortezomib, thalidomide, dexamethasone, and panobinostat for patients with relapsed multiple myeloma (MUK-six): A multicentre, open-label, phase 1\/2 trial","volume":"3","author":"Popat","year":"2016","journal-title":"Lancet Haematol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41408-021-00407-5","article-title":"Phase 1 open-label study of panobinostat, lenalidomide, bortezomib + dexamethasone in relapsed and relapsed\/refractory multiple myeloma","volume":"11","author":"Laubach","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1158\/1078-0432.CCR-16-2526","article-title":"Ricolinostat, the first selective histone deacetylase 6 inhibitor, in combination with bortezomib and dexamethasone for relapsed or refractory multiple myeloma","volume":"23","author":"Vogl","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/S1470-2045(16)30375-8","article-title":"Ricolinostat plus lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A multicentre phase 1b trial","volume":"17","author":"Yee","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1182\/blood-2014-05-573741","article-title":"Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma","volume":"125","author":"Kumar","year":"2015","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1158\/1078-0432.CCR-19-1899","article-title":"A Phase I Study of Ruxolitinib, Lenalidomide, and Steroids for Patients with Relapsed\/Refractory Multiple Myeloma","volume":"26","author":"Berenson","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_66","first-page":"PO.18.00070","article-title":"Vemurafenib in Patients with Relapsed Refractory Multiple Myeloma Harboring BRAF V600 Mutations: A Cohort of the Histology-Independent VE-BASKET Study","volume":"2","author":"Raje","year":"2018","journal-title":"JCO Precis Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1182\/blood-2020-142600","article-title":"Safety and Preliminary Efficacy Results from a Phase II Study Evaluating Combined BRAF and MEK Inhibition in Relapsed\/Refractory Multiple Myeloma (rrMM) Patients with Activating BRAF V600E Mutations: The GMMG-Birma Trial","volume":"136","author":"Raab","year":"2020","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4617","DOI":"10.1002\/cncr.30892","article-title":"A Phase 1 and 2 study of Filanesib alone and in combination with low-dose dexamethasone in relapsed\/refractory multiple myeloma","volume":"123","author":"Shah","year":"2017","journal-title":"Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/s41408-019-0240-6","article-title":"A phase 1 study of filanesib, carfilzomib, and dexamethasone in patients with relapsed and\/or refractory multiple myeloma","volume":"9","author":"Lee","year":"2019","journal-title":"Blood Cancer J."},{"key":"ref_70","first-page":"522","article-title":"Safety and Efficacy of Filanesib in Combination with Pomalidomide and Dexamethasone in Refractory MM Patients. Phase Ib\/II Pomdefil Clinical Trial Conducted By the Spanish MM Group","volume":"92","author":"Ocio","year":"2016","journal-title":"Blood"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/20\/5210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:16:52Z","timestamp":1760167012000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/20\/5210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,18]]},"references-count":70,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["cancers13205210"],"URL":"https:\/\/doi.org\/10.3390\/cancers13205210","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,18]]}}}