{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:43:06Z","timestamp":1792395786622,"version":"4.4.0"},"reference-count":98,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"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>Mezigomide is an oral cereblon E3 ligase modulator (CELMoD) that is under clinical investigation in patients with relapsed\/refractory (RR) multiple myeloma (MM). Like other CELMoD compounds, mezigdomide acts by altering the conformation of cereblon within the cullin 4A ring ligase\u2013cereblon (CRL4CRBN) E3 ubiquitin ligase complex, thereby recruiting novel protein substrates for selective proteasomal degradation. These include two critical lymphoid transcription factors, Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3), also known as Ikaros and Aiolos, which have important roles in the development and differentiation of hematopoietic cells, in MM pathobiology, and in suppressing the expression of interferon-stimulating genes and T-cell stimulation. Among the CELMoDs, mezigdomide has the greatest cereblon-binding potency, plus the greatest potency for the degradation of Ikaros and Aiolos and subsequent downstream antimyeloma effects. Preclinical studies of mezigdomide have demonstrated its anti-proliferative and apoptotic effects in MM, along with its immune-stimulatory effects and its synergistic activity with other antimyeloma agents, including in lenalidomide-\/pomalidomide-resistant MM cell lines and mouse xenograft models. Early-phase clinical trial data indicate notable activity in heavily pretreated patients with RRMM, including those with triple-class-refractory disease, together with a tolerable and manageable safety profile. This review summarizes current preclinical and clinical findings with mezigdomide and its potential future roles in the treatment of MM.<\/jats:p>","DOI":"10.3390\/cancers16061166","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T12:02:39Z","timestamp":1710504159000},"page":"1166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Mezigdomide\u2014A Novel Cereblon E3 Ligase Modulator under Investigation in Relapsed\/Refractory Multiple Myeloma"],"prefix":"10.3390","volume":"16","author":[{"given":"Monique A.","family":"Hartley-Brown","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, 450 Brookline Avenue, Dana 1B02, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifton C.","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, 450 Brookline Avenue, Dana 1B02, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, 450 Brookline Avenue, Dana 1B02, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shonali","family":"Midha","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, 450 Brookline Avenue, Dana 1B02, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob P.","family":"Laubach","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, 450 Brookline Avenue, Dana 1B02, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, 450 Brookline Avenue, Dana 1B02, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1200\/JCO.2011.37.8919","article-title":"The 39th David A. Karnofsky Lecture: Bench-to-Bedside Translation of Targeted Therapies in Multiple Myeloma","volume":"30","author":"Anderson","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1200\/JCO.19.02515","article-title":"Long-Term Follow-up Results of Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy and Risk-Adapted Maintenance Approach in Newly Diagnosed Multiple Myeloma","volume":"38","author":"Joseph","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e263","DOI":"10.1093\/oncolo\/oyad053","article-title":"Impact of Treatment Sequencing on Overall Survival in Patients with Transplant-Ineligible Newly Diagnosed Myeloma","volume":"28","author":"Fonseca","year":"2023","journal-title":"Oncologist"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41408-023-00804-y","article-title":"Clinical Evidence for Immune-Based Strategies in Early-Line Multiple Myeloma: Current Challenges in Decision-Making for Subsequent Therapy","volume":"13","author":"Raje","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Benda, M.A., Ulmer, H., Weger, R., Reimann, P., Lang, T., Pichler, P., Winder, T., Hartmann, B., Strassl, I., and Krauth, M.T. (2023). Attrition Rates in Multiple Myeloma Treatment under Real World Conditions-an Analysis from the Austrian Myeloma Registry (Amr). Cancers, 15.","DOI":"10.3390\/cancers15030962"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/s41408-023-00883-x","article-title":"Redefining Attrition in Multiple Myeloma (Mm): A Canadian Myeloma Research Group (Cmrg) Analysis","volume":"13","author":"McCurdy","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8","DOI":"10.6004\/jnccn.2022.0002","article-title":"Nccn Guidelines(R) Insights: Multiple Myeloma, Version 3.2022","volume":"20","author":"Callander","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: Globocan Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer Statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_10","unstructured":"NIH National Cancer Institute Surveillance, Epidemiology, and End Results Program (2024, February 16). Cancer Stat Facts: Myeloma, Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/mulmy.html."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/s41408-018-0141-0","article-title":"Interpreting Clinical Trial Data in Multiple Myeloma: Translating Findings to the Real-World Setting","volume":"8","author":"Richardson","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_12","first-page":"564","article-title":"The Evolving Role of Transplantation in Multiple Myeloma: The Need for a Heterogeneous Approach to a Heterogeneous Disease","volume":"16","author":"Gandolfi","year":"2018","journal-title":"Clin. Adv. Hematol. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.annonc.2020.11.014","article-title":"Multiple Myeloma: Eha-Esmo Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up","volume":"32","author":"Dimopoulos","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1002\/ajh.26590","article-title":"Multiple Myeloma: 2022 Update on Diagnosis, Risk Stratification, and Management","volume":"97","author":"Rajkumar","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41408-022-00733-2","article-title":"I-Open: Inferior Outcomes of Penta-Refractory Compared to Penta-Exposed Multiple Myeloma Patients","volume":"12","author":"Gill","year":"2022","journal-title":"Blood Cancer J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4464","DOI":"10.3390\/curroncol29070355","article-title":"Clinical Management of Triple-Class Refractory Multiple Myeloma: A Review of Current Strategies and Emerging Therapies","volume":"29","author":"Stalker","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/jha2.709","article-title":"Selinexor: Targeting a Novel Pathway in Multiple Myeloma","volume":"4","author":"Mo","year":"2023","journal-title":"EJHaem"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1358\/dot.2022.58.8.3367680","article-title":"Melphalan Flufenamide for Relapsed\/Refractory Multiple Myeloma","volume":"58","author":"Nadeem","year":"2022","journal-title":"Drugs Today"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3322\/caac.21771","article-title":"Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma: A Comprehensive Review of Current Data and Implications for Clinical Practice","volume":"73","author":"Parikh","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1182\/hematology.2022000334","article-title":"Antibodies and Bispecifics for Multiple Myeloma: Effective Effector Therapy","volume":"2022","author":"Cipkar","year":"2022","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1032775","DOI":"10.3389\/fonc.2022.1032775","article-title":"Bispecific Antibodies in Multiple Myeloma Treatment: A Journey in Progress","volume":"12","author":"Cho","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"705","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":"ref_23","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1056\/NEJMoa2213614","article-title":"Ide-Cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma","volume":"388","author":"Ailawadhi","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"314","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":"ref_25","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1056\/NEJMoa2303379","article-title":"Cilta-Cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma","volume":"389","author":"Dhakal","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1056\/NEJMoa2203478","article-title":"Teclistamab in Relapsed or Refractory Multiple Myeloma","volume":"387","author":"Moreau","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1056\/NEJMoa2204591","article-title":"Talquetamab, a T-Cell-Redirecting Gprc5d Bispecific Antibody for Multiple Myeloma","volume":"387","author":"Chari","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1038\/s41591-023-02528-9","article-title":"Elranatamab in Relapsed or Refractory Multiple Myeloma: Phase 2 Magnetismm-3 Trial Results","volume":"29","author":"Lesokhin","year":"2023","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4198","DOI":"10.1002\/cncr.33809","article-title":"Longer Term Outcomes with Single-Agent Belantamab Mafodotin in Patients with Relapsed or Refractory Multiple Myeloma: 13-Month Follow-up from the Pivotal Dreamm-2 Study","volume":"127","author":"Lonial","year":"2021","journal-title":"Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1111\/bjh.14514","article-title":"Guidelines for Screening and Management of Late and Long-Term Consequences of Myeloma and Its Treatment","volume":"176","author":"Snowden","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41408-021-00432-4","article-title":"Management of Patients with Multiple Myeloma Beyond the Clinical-Trial Setting: Understanding the Balance between Efficacy, Safety and Tolerability, and Quality of Life","volume":"11","author":"Terpos","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e20021","DOI":"10.1200\/JCO.2022.40.16_suppl.e20021","article-title":"Ethical Challenges with Car T Slot Allocation with Idecabtagene Vicleucel Manufacturing Access","volume":"40","author":"Kourelis","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1056\/NEJMoa2303194","article-title":"Mezigdomide Plus Dexamethasone in Relapsed and Refractory Multiple Myeloma","volume":"389","author":"Richardson","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"LaPlante, G., and Zhang, W. (2021). Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors. Cancers, 13.","DOI":"10.3390\/cancers13123079"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6521","DOI":"10.18632\/oncotarget.6658","article-title":"Novel Strategies to Target the Ubiquitin Proteasome System in Multiple Myeloma","volume":"7","author":"Lub","year":"2016","journal-title":"Oncotarget"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"517","DOI":"10.2174\/1568009614666140804154511","article-title":"Overview of Proteasome Inhibitor-Based Anti-Cancer Therapies: Perspective on Bortezomib and Second Generation Proteasome Inhibitors Versus Future Generation Inhibitors of Ubiquitin-Proteasome System","volume":"14","author":"Dou","year":"2014","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s10555-017-9707-8","article-title":"The Proteasome and Proteasome Inhibitors in Multiple Myeloma","volume":"36","author":"Gandolfi","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1080\/14789450.2022.2142564","article-title":"The Role of E3 Ubiquitin Ligase in Multiple Myeloma: Potential for Cereblon E3 Ligase Modulators in the Treatment of Relapsed\/Refractory Disease","volume":"19","author":"Richardson","year":"2022","journal-title":"Expert. Rev. Proteom."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1565","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":"ref_40","doi-asserted-by":"crossref","first-page":"4050","DOI":"10.1182\/blood-2005-07-2817","article-title":"Combination Therapy with Lenalidomide Plus Dexamethasone (Rev\/Dex) for Newly Diagnosed Myeloma","volume":"106","author":"Rajkumar","year":"2005","journal-title":"Blood"},{"key":"ref_41","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_42","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.1182\/blood-2011-05-356063","article-title":"Cereblon Expression Is Required for the Antimyeloma Activity of Lenalidomide and Pomalidomide","volume":"118","author":"Zhu","year":"2011","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6648","DOI":"10.1021\/acs.jmedchem.9b01928","article-title":"Discovery of Crbn E3 Ligase Modulator Cc-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma","volume":"63","author":"Hansen","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1056\/NEJMe2307370","article-title":"Mezigdomide and Multiple Myeloma","volume":"389","author":"Shortt","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_45","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":"Kronke","year":"2014","journal-title":"Science"},{"key":"ref_46","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_47","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1016\/j.molimm.2011.03.006","article-title":"The Ikaros Gene Family: Transcriptional Regulators of Hematopoiesis and Immunity","volume":"48","author":"John","year":"2011","journal-title":"Mol. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1182\/blood-2018-05-850727","article-title":"Imids Prime Myeloma Cells for Daratumumab-Mediated Cytotoxicity through Loss of Ikaros and Aiolos","volume":"132","author":"Fedele","year":"2018","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/bjh.12708","article-title":"Immunomodulatory Agents Lenalidomide and Pomalidomide Co-Stimulate T Cells by Inducing Degradation of T Cell Repressors Ikaros and Aiolos Via Modulation of the E3 Ubiquitin Ligase Complex CRL4CRBN","volume":"164","author":"Gandhi","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1021\/acs.jmedchem.6b01921","article-title":"A Cereblon Modulator (Cc-220) with Improved Degradation of Ikaros and Aiolos","volume":"61","author":"Matyskiela","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1126\/science.add7574","article-title":"Molecular Glue Celmod Compounds Are Regulators of Cereblon Conformation","volume":"378","author":"Watson","year":"2022","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1182\/blood-2021-150971","article-title":"Potent Ikaros Degradation by the Cereblon E3 Ligase Modulator Cc-92480 Is Effective in Combination with Menin-Mll1 Inhibition in Mll1-Rearranged and Npm1-Mutant Aml","volume":"138","author":"Bourgeois","year":"2021","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1182\/blood.2021015119","article-title":"Targeting Imid-Resistant T-Cell Lymphoma","volume":"139","author":"Liang","year":"2022","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1182\/blood.2021014701","article-title":"Overcoming Imid Resistance in T-Cell Lymphomas through Potent Degradation of Zfp91 and Ikzf1","volume":"139","author":"Wu","year":"2022","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Barankiewicz, J., Salomon-Perzynski, A., Misiewicz-Krzeminska, I., and Lech-Maranda, E. (2022). CRL4CRBN E3 Ligase Complex as a Therapeutic Target in Multiple Myeloma. Cancers, 14.","DOI":"10.3390\/cancers14184492"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"632399","DOI":"10.3389\/fimmu.2021.632399","article-title":"Understanding the Role of T-Cells in the Antimyeloma Effect of Immunomodulatory Drugs","volume":"12","author":"Prince","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1182\/blood-2019-124338","article-title":"Cc-92480 Is a Novel Cereblon E3 Ligase Modulator with Enhanced Tumoricidal and Immunomodulatory Activity against Sensitive and Resistant Multiple Myeloma Cells","volume":"134","author":"Havens","year":"2019","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7054","DOI":"10.1182\/blood-2022-157987","article-title":"Synergistic Antitumor Activity of Alnuctamab (Alnuc; Bms-986349; Cc-93269), a Bcma 2+1 T Cell Engager (Tce), and Celmod Agents in Multiple Myeloma (Mm) Preclinical Models","volume":"140","author":"Paiva","year":"2022","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1182\/blood-2021-151542","article-title":"Large-Scale Mass Cytometry Reveals Significant Activation of Innate and Adaptive Immunity in Bone Marrow Tumor Microenvironment of Iberdomide-Treated Myeloma Patients","volume":"138","author":"Amatangelo","year":"2021","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4686","DOI":"10.1182\/blood-2023-187748","article-title":"Mezigdomide Treatment in Relapsed-Refractory Myeloma Patients Shifts Bone Marrow Nk and T Cell Populations from Exhaustion to Activation","volume":"142","author":"Chen","year":"2023","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1182\/blood-2023-189445","article-title":"Mezigdomide Reverses T-Cell Exhaustion through Degradation of Aiolos\/Ikaros and Reinvigoration of Cytokine Production Pathways","volume":"142","author":"Chiu","year":"2023","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.18632\/oncotarget.27973","article-title":"Developing Next Generation Immunomodulatory Drugs and Their Combinations in Multiple Myeloma","volume":"12","author":"Thakurta","year":"2021","journal-title":"Oncotarget"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1182\/blood-2019-124345","article-title":"Cc-92480, a Novel Cereblon E3 Ligase Modulator, Is Synergistic with Dexamethasone, Bortezomib, and Daratumumab in Multiple Myeloma","volume":"134","author":"Wong","year":"2019","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1182\/blood-2021-153994","article-title":"Pre-Clinical and Clinical Immunomodulatory Effects of Pomalidomide or Cc-92480 in Combination with Bortezomib in Multiple Myeloma","volume":"138","author":"Bjorklund","year":"2021","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1182\/blood-2021-153907","article-title":"Cc-92480 Enhances Cell-Autonomous Cytotoxicity through Blockade of G 2\/M Transition When Combined with Bortezomib\/Dexamethasone in Pre-Clinical Multiple Myeloma","volume":"138","author":"Bjorklund","year":"2021","journal-title":"Blood"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"S161","DOI":"10.1016\/S2152-2650(22)00560-2","article-title":"P-230: Preclinical and Translational Biomarker Analysis to Support Further Clinical Development and Dose Optimization of Mezigdomide (Mezi; Cc-92480) in Combination with Either Bortezomib or Carfilzomib","volume":"22","author":"Amatangelo","year":"2022","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1182\/blood-2023-178881","article-title":"Preclinical and Translational Biomarker Analyses to Inform Clinical Development of Mezigdomide (Cc-92480) in Combination with Dexamethasone and Daratumumab in Multiple Myeloma","volume":"142","author":"Chow","year":"2023","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7108","DOI":"10.1182\/blood-2022-157939","article-title":"Mezigdomide (Cc-92480), a Novel Cereblon E3 Ligase Modulator, Induces Vulnerability of Multiple Myeloma Cells to T-Cell-Mediated Killing","volume":"140","author":"Gaffney","year":"2022","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3291","DOI":"10.1007\/s12325-023-02551-9","article-title":"Bispecific Monoclonal Antibodies in Multiple Myeloma: Data from Ash 2022: A Podcast","volume":"40","author":"Landgren","year":"2023","journal-title":"Adv. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4659","DOI":"10.1182\/blood-2023-174253","article-title":"Early Intervention with Celmods, but Not Imids, Prevents Relapse to Forimtamig Driven by Gprc5d-Negative Myeloma Cells","volume":"142","author":"Eckmann","year":"2023","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"7070","DOI":"10.1182\/blood-2022-157927","article-title":"Suppression of Myeloid Cell-Derived Proinflammatory Cytokines with Celmod Agents: Implications for Crs with T-Cell Engagers (Tces)","volume":"140","author":"Jeyaraju","year":"2022","journal-title":"Blood"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1182\/blood-2021-150641","article-title":"Super-Enhancer Driven Regulation of Cks1b in Multiple Myeloma: Implications in Mediating Response to Bet Inhibitor and Celmod Agent Combination","volume":"138","author":"Ahsan","year":"2021","journal-title":"Blood"},{"key":"ref_73","first-page":"131","article-title":"IMiD Imid Resistance in Multiple Myeloma: Current Understanding of the Underpinning Biology and Clinical Impact","volume":"142","author":"Bird","year":"2023","journal-title":"Blood"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1182\/blood-2022-166444","article-title":"Multiomics Analysis of Imid\/Celmod Resistant Multiple Myeloma Models Uncovers Novel and Targetable Vulnerabilities in the Srebp Lipid Synthesis Pathway","volume":"140","author":"Bird","year":"2022","journal-title":"Blood"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"9964","DOI":"10.1182\/blood-2022-169550","article-title":"Crbn Structural Changes, Copy Number Changes and Cop9 Signalosome Subunits Gene Expression Mediate Sensitivity to New Celmod Compound Cc-92480 in Multiple Myeloma Patients","volume":"140","author":"Tilmont","year":"2022","journal-title":"Blood"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1182\/blood-2023-179986","article-title":"Investigating the Functional Impact of Crbn Mutations on Response to Imid\/Celmod Agents in Myeloma","volume":"142","author":"Chrisochoidou","year":"2023","journal-title":"Blood"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1182\/blood.2020007081","article-title":"Multiple Cereblon Genetic Changes Are Associated with Acquired Resistance to Lenalidomide or Pomalidomide in Multiple Myeloma","volume":"137","author":"Gooding","year":"2021","journal-title":"Blood"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e2111391118","DOI":"10.1073\/pnas.2111391118","article-title":"USP15 Antagonizes CRL4CRBN-Mediated Ubiquitylation of Glutamine Synthetase and Neosubstrates","volume":"118","author":"Nguyen","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1016\/S2152-2650(23)01616-6","article-title":"Oa-49 Mezigdomide (Mezi) Plus Dexamethasone (Dex) and Bortezomib (Bort) or Carfilzomib (Cfz) in Patients (Pts) with Relapsed\/Refractory Multiple Myeloma (Rrmm): Results from the Cc-92480-Mm-002 Trial","volume":"23","author":"Oriol","year":"2023","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_80","first-page":"S181","article-title":"P-265 Mezigdomide (Mezi) Monotherapy in Relapsed\/Refractory Multiple Myeloma (Rrmm): Results from the Cc-92480-Mm-001 Trial","volume":"23","author":"Goldsmith","year":"2023","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1182\/blood-2023-174443","article-title":"Mezigdomide (Mezi) Plus Dexamethasone (Dex) and Daratumumab (Dara) or Elotuzumab (Elo) in Patients (Pts) with Relapsed\/Refractory Multiple Myeloma (Rrmm): Results from the Cc-92480-Mm-002 Trial","volume":"142","author":"Richardson","year":"2023","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1002\/psp4.13024","article-title":"Model Based Assessment of Food and Acid Reducing Agent Effects on Oral Absorption of Mezigdomide (Cc-92480), a Novel Cereblon E3 Ligase Modulator","volume":"12","author":"Wu","year":"2023","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1182\/blood-2020-137161","article-title":"Dose- and Schedule-Dependent Immunomodulatory Effects of the Novel Celmod Agent Cc-92480 in Patients with Relapsed\/Refractory Multiple Myeloma","volume":"136","author":"Wong","year":"2020","journal-title":"Blood"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1634\/theoncologist.2016-0104","article-title":"Analysis of Real-World Data on Overall Survival in Multiple Myeloma Patients with \u22653 Prior Lines of Therapy Including a Proteasome Inhibitor (Pi) and an Immunomodulatory Drug (Imid), or Double Refractory to a Pi and an Imid","volume":"21","author":"Usmani","year":"2016","journal-title":"Oncologist"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1038\/s41375-019-0435-7","article-title":"Outcomes of Patients with Multiple Myeloma Refractory to Cd38-Targeted Monoclonal Antibody Therapy","volume":"33","author":"Gandhi","year":"2019","journal-title":"Leukemia"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa1903455","article-title":"Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma","volume":"381","author":"Chari","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_87","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_88","doi-asserted-by":"crossref","first-page":"5008","DOI":"10.1200\/JCO.2009.23.6802","article-title":"Pomalidomide (Cc4047) Plus Low-Dose Dexamethasone as Therapy for Relapsed Multiple Myeloma","volume":"27","author":"Lacy","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1182\/blood-2012-08-450742","article-title":"Phase 1 Study of Pomalidomide Mtd, Safety, and Efficacy in Patients with Refractory Multiple Myeloma Who Have Received Lenalidomide and Bortezomib","volume":"121","author":"Richardson","year":"2013","journal-title":"Blood"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1182\/blood-2013-11-538835","article-title":"Pomalidomide Alone or in Combination with Low-Dose Dexamethasone in Relapsed and Refractory Multiple Myeloma: A Randomized Phase 2 Study","volume":"123","author":"Richardson","year":"2014","journal-title":"Blood"},{"key":"ref_91","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_92","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1182\/blood-2015-05-643320","article-title":"Carfilzomib, Pomalidomide, and Dexamethasone for Relapsed or Refractory Myeloma","volume":"126","author":"Shah","year":"2015","journal-title":"Blood"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1038\/leu.2017.173","article-title":"Pomalidomide, Bortezomib and Low-Dose Dexamethasone in Lenalidomide-Refractory and Proteasome Inhibitor-Exposed Myeloma","volume":"31","author":"Richardson","year":"2017","journal-title":"Leukemia"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1182\/blood-2017-05-785246","article-title":"Daratumumab Plus Pomalidomide and Dexamethasone in Relapsed and\/or Refractory Multiple Myeloma","volume":"130","author":"Chari","year":"2017","journal-title":"Blood"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"801","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":"ref_96","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1016\/S0140-6736(19)32556-5","article-title":"Isatuximab Plus Pomalidomide and Low-Dose Dexamethasone Versus Pomalidomide and Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple Myeloma (Icaria-Mm): A Randomised, Multicentre, Open-Label, Phase 3 Study","volume":"394","author":"Attal","year":"2019","journal-title":"Lancet"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"S495","DOI":"10.1016\/S2152-2650(23)01446-5","article-title":"Mm-372 a Phase Iii, Two-Stage, Randomized Study of Mezigdomide, Bortezomib, and Dexamethasone (Mezivd) Versus Pomalidomide, Bortezomib, and Dexamethasone (Pvd) in Relapsed\/Refractory Multiple Myeloma (Rrmm): Successor-1","volume":"23","author":"Richardson","year":"2023","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"TPS8070","DOI":"10.1200\/JCO.2023.41.16_suppl.TPS8070","article-title":"A Phase 3, Two-Stage, Randomized Study of Mezigdomide, Carfilzomib, and Dexamethasone (Mezikd) Versus Carfilzomib and Dexamethasone (Kd) in Relapsed\/Refractory Multiple Myeloma (Rrmm): Successor-2","volume":"42","author":"Richardson","year":"2023","journal-title":"J. Clin. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/6\/1166\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:14:26Z","timestamp":1760105666000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/6\/1166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,15]]},"references-count":98,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["cancers16061166"],"URL":"https:\/\/doi.org\/10.3390\/cancers16061166","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,15]]}}}