Padala SA, Barsouk A, Barsouk A, Rawla P, Vakiti A, Kolhe R, et al. Epidemiology, staging, and management of multiple myeloma. Med Sci. 2021;9(1):3. https://doi.org/10.3390/medsci9010003.

Article  CAS  Google Scholar 

Fonseca R, Abouzaid S, Bonafede M, Cai Q, Parikh K, Cosler L, Richardson P. Trends in overall survival and costs of multiple myeloma, 2000–2014. Leukemia. 2017;31:1915–21. https://doi.org/10.1038/leu.2016.380.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kumar SK, Dimopoulos MA, Kastritis E, Terpos E, Nahi H, Goldschmidt H, et al. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Leukemia. 2017;31:2443–8. https://doi.org/10.1038/leu.2017.138.

Article  CAS  PubMed  Google Scholar 

Minařík J, Ševčíková S. Immunomodulatory agents for multiple myeloma. Cancers (Basel). 2022;14(23):5759. https://doi.org/10.3390/cancers14235759.

Article  PubMed  PubMed Central  Google Scholar 

Ito T, Handa H. Cereblon and its downstream substrates as molecular targets of immunomodulatory drugs History of immunomodulatory drugs (IMiDs). Int J Hematol. 2016;104:293–9. https://doi.org/10.1007/s12185-016-2073-4.

Article  CAS  PubMed  Google Scholar 

Hideshima T, Raje N, Richardson PG, Anderson KC. A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. Ther Clin Risk Manag. 2008;4(1):129–36. https://doi.org/10.2147/tcrm.s1445.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martinez-Høyer S, Karsan A. Mechanisms of lenalidomide sensitivity and resistance. Exp Hematol. 2020;91:22–31. https://doi.org/10.1016/j.exphem.2020.09.196.

Article  CAS  PubMed  Google Scholar 

Zhu YX, Shi CX, Bruins LA, Wang X, Riggs DL, Porter B, et al. Identification of lenalidomide resistance pathways in myeloma and targeted resensitization using cereblon replacement, inhibition of STAT3 or targeting of IRF4. Blood Cancer J. 2019;9(2):19. https://doi.org/10.1038/s41408-019-0173-0.

Article  PubMed  PubMed Central  Google Scholar 

Furqan M, Mukhi N, Lee B, Liu D. Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application. Biomark Res. 2013;1(1):5. https://doi.org/10.1186/2050-7771-1-5.

Article  PubMed  PubMed Central  Google Scholar 

Ogiya D, Liu J, Ohguchi H, Kurata K, Samur MK, Tai Y-T, et al. The JAK-STAT pathway regulates CD38 on myeloma cells in the bone marrow microenvironment: therapeutic implications. Blood. 2020;136(20):2334–45. https://doi.org/10.1182/blood.2019004332.

Article  PubMed  PubMed Central  Google Scholar 

Podar K, Chauhan D, Anderson KC. Bone marrow microenvironment and the identification of new targets for myeloma therapy. Leukemia. 2009;23:10–24. https://doi.org/10.1038/leu.2008.259.

Article  CAS  PubMed  Google Scholar 

Li J, Favata M, Kelley JA, Caulder E, Thomas B, Wen X, et al. INCB16562, a JAK1/2 selective inhibitor, is efficacious against multiple myeloma cells and reverses the protective effects of cytokine and stromal cell support. Neoplasia. 2010;12:28–38. https://doi.org/10.1593/neo.91192.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sanchez E, Li M, Patil S, Soof CM, Nosrati JD, Schlossberg RE, et al. The anti-myeloma effects of the selective JAK1 inhibitor (INCB052793) alone and in combination in vitro and in vivo. Ann Hematol. 2019;98:691–703. https://doi.org/10.1007/s00277-019-03595-0.

Article  CAS  PubMed  Google Scholar 

Gupta N, Mayer D. Interaction of JAK with steroid receptor function. JAKSTAT. 2013;2: e24911. https://doi.org/10.4161/jkst.24911.

Article  PubMed  PubMed Central  Google Scholar 

Monaghan KA, Khong T, Burns CJ, Spencer A. The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells. Leukemia. 2011;25:1891–9. https://doi.org/10.1038/leu.2011.175.

Article  CAS  PubMed  Google Scholar 

Ramakrishnan V, Kimlinger T, Haug J, Timm M, Wellik L, Halling T, et al. TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD451 myeloma cells. Am J Hematol. 2010;85:675–86. https://doi.org/10.1002/ajh.21785.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu N, Yu E, Ng N, Li M, Bujarski S, Hekmati A, et al. The JAK1/2 inhibitor ruxolitinib downregulates the immune checkpoint protein B7H3 in multiple myeloma. Hematol Oncol. 2023;41:578–82. https://doi.org/10.1002/hon.3071.

Article  CAS  PubMed  Google Scholar 

Chen H, Sanchez E, Li M, Wang C, Gillespie A, Shvartsur A, et al. Anti-myeloma activity by the combination of the JAK2 inhibitor ruxolitinib with lenalidomide and corticosteroids. Blood. 2014;124(21):2114. https://doi.org/10.1182/blood.V124.21.2114.2114.

Article  Google Scholar 

Chen H, Li M, Ng N, Yu E, Bujarski S, Yin Z, et al. Ruxolitinib reverses checkpoint inhibition by reducing programmed cell death ligand-1 (PD-L1) expression and increases anti-tumour effects of T cells in multiple myeloma. Br J Haematol. 2020;192:568–76. https://doi.org/10.1111/bjh.17282.

Article  CAS  PubMed  Google Scholar 

Chen H, Li M, Sanchez E, Soof CM, Bujarski S, Ng N, et al. JAK1/2 pathway inhibition suppresses M2 polarization and overcomes resistance of myeloma to lenalidomide by reducing TRIB1, MUC1, CD44, CXCL12, and CXCR4 expression. Br J Haematol. 2020;188:283–94. https://doi.org/10.1111/bjh.16158.

Article  CAS  PubMed  Google Scholar 

Plosker GL. Ruxolitinib: a review of its use in patients with myelofibrosis. Drugs. 2015;75:297–308. https://doi.org/10.1007/s40265-015-0351-8.

Article  CAS  PubMed  Google Scholar 

Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372:426–35. https://doi.org/10.1056/nejmoa1409002.

Article  PubMed  PubMed Central  Google Scholar 

De Oliveira MB, Fook-Alves VL, Eugenio AIP, Fernando RC, Sanson FG, De Carvalho MF, et al. Anti-myeloma effects of ruxolitinib combined with bortezomib and lenalidomide: a rationale for JAK/STAT pathway inhibition in myeloma patients. Cancer Lett. 2017;403:206–15. https://doi.org/10.1016/j.canlet.2017.06.016.

Article  CAS  PubMed  Google Scholar 

Krasil’nikov M, Shatskaya V. Signal transducer and activator of transcription-3 and phosphatidylinositol-3 kinase as coordinate regulators of melanoma cell response to glucocorticoid hormones. J Steroid Biochem Mol Biol. 2002;82:369–76.

Article  PubMed  Google Scholar 

Shi JG, Chen X, McGee RF, Landman RR, Emm T, Lo Y, et al. The pharmacokinetics, pharmacodynamics, and safety of orally dosed INCB018424 phosphate in healthy volunteers. J Clin Pharmacol. 2011;51:1644–54. https://doi.org/10.1177/0091270010389469.

Article  CAS  PubMed  Google Scholar 

Uchiyama H, Barut BA, Mohrbacher AF, Chauhan D, Anderson KC. Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion. Blood. 1993;82:3712–20.

Article  CAS  PubMed  Google Scholar 

Chauhan D, Uchiyama H, Akbarali Y, Urashima M, Yamamoto K-L, Libermann TA, et al. Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-KB. Blood. 1996;87(3):1104–12.

Article  CAS  PubMed  Google Scholar 

Maïga S, Gomez-Bougie P, Bonnaud S, Gratas C, Moreau P, Le Gouill S, et al. Paradoxical effect of lenalidomide on cytokine/growth factor profiles in multiple myeloma. Br J Cancer. 2013;108:1801–6. https://doi.org/10.1038/bjc.2013.186.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Berenson JR, Kim C, Bujarski S, To J, Spektor TM, Martinez D, et al. A phase 1 study of ruxolitinib, steroids and lenalidomide for relapsed/refractory multiple myeloma patients. Hematol Oncol. 2022;40:906–13. https://doi.org/10.1002/hon.3066.

Article  CAS  PubMed  Google Scholar 

Berenson JR, To J, Spektor TM, Martinez D, Turner C, Sanchez A, et al. A phase I study of ruxolitinib, lenalidomide, and steroids for patients with relapsed/refractory multiple myeloma. Clin Cancer Res. 2020;26:2346–53. https://doi.org/10.1158/1078-0432.CCR-19-1899.

Article  CAS  PubMed  Google Scholar 

Berenson JR, Martinez D, Safiae T, Boccia R, Yang H, Moezi M, et al. Ruxolitinib and methylprednisolone for treatment of patients with relapsed/refractory multiple myeloma. Br J Haematol. 2022;200:722–30.

Article  PubMed  Google Scholar 

Loscocco GG, Vannucchi AM. Role of JAK inhibitors in myeloproliferative neoplasms: current point of view and perspectives. Int J Hematol. 2022;115(5):626–44. https://doi.org/10.1007/S12185-022-03335-7.

Article  CAS  PubMed  Google Scholar 

Hu X, li J, Fu M, Zhao X, Wang W. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021;6(1):402. https://doi.org/10.1038/s41392-021-00791-1.