Vol 14 (2023): Continuous Publishing
Case report
Published online: 2023-11-29
Ruxolitinib as a primary treatment for multiple myeloma in a patient with primary myelofibrosis? A case report and the review of the literature
DOI: 10.5603/hicp.95649
Hematology in Clinical Practice 2023;14:41-45.
Abstract
An 80-year-old female with a history of primary myelofibrosis was admitted to the hospital due to worsening symptoms of the primary disease. A secondary tumor — multiple myeloma (MM) — was revealed during the diagnostic process. Monotherapy with a JAK inhibitor (ruxolitinib) was administered, and the severity of both malignancies was alleviated. This article includes a short review of secondary malignancies correlated with PMF and the state of knowledge on using JAK inhibitors, mainly ruxolitinib, in treating MM.
Keywords: primary myelofibrosismultiple myelomaruxolitinibinhibitor
References
- Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022; 140(11): 1200–1228.
- Pardanani A, Lasho TL, Finke C, et al. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia. 2007; 21(9): 1960–1963.
- Tefferi A, Guglielmelli P, Larson DR, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014; 124(16): 2507–13; quiz 2615.
- Tefferi A. Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023; 98(5): 801–821.
- Genthon A, Killian M, Mertz P, et al. [Myelofibrosis: a review] [In French]. Rev Med Interne. 2021; 42(2): 101–109.
- Garmezy B, Schaefer JK, Mercer J, et al. A provider's guide to primary myelofibrosis: pathophysiology, diagnosis, and management. Blood Rev. 2021; 45: 100691.
- Castillo-Tokumori F, Talati C, Al Ali N, et al. Retrospective analysis of the clinical use and benefit of lenalidomide and thalidomide in myelofibrosis. Clin Lymphoma Myeloma Leuk. 2020; 20(12): e956–e960.
- Daver N, Cortes J, Newberry K, et al. Ruxolitinib in combination with lenalidomide as therapy for patients with myelofibrosis. Haematologica. 2015; 100(8): 1058–1063.
- Tremblay D, Mascarenhas J. Next generation therapeutics for thetreatment of myelofibrosis. Cells. 2021; 10(5).
- Datta J, Dai X, Bianchi A, et al. Combined MEK and STAT3 iInhibition uncovers stromal plasticity by enriching for cancer-associated fibroblasts with mesenchymal stem cell-like features to overcome immunotherapy resistance in pancreatic cancer. Gastroenterology. 2022; 163(6): 1593–1612.
- Lu C, Talukder A, Savage NM, et al. JAK-STAT-mediated chronic inflammation impairs cytotoxic T lymphocyte activation to decrease anti-PD-1 immunotherapy efficacy in pancreatic cancer. Oncoimmunology. 2017; 6(3): e1291106.
- Keenan C, Nichols KE, Albeituni S. Use of the JAK inhibitor ruxolitinib in the treatment of hemophagocytic lymphohistiocytosis. Front Immunol. 2021; 12: 614704.
- Levy G, Guglielmelli P, Langmuir P, et al. JAK inhibitors and COVID-19. J Immunother Cancer. 2022; 10(4).
- Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012; 366(9): 799–807.
- Vannucchi AM, Kantarjian HM, Kiladjian JJ, et al. COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015; 100(9): 1139–1145.
- Zeiser R, Polverelli N, Ram R, et al. REACH3 Investigators. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021; 385(3): 228–238.
- Zeiser R, von Bubnoff N, Butler J, et al. REACH2 Trial Group. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020; 382(19): 1800–1810.
- Kiladjian JJ, Zachee P, Hino M, et al. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020; 7(3): e226–e237.
- Landtblom AR, Bower H, Andersson TML, et al. Second malignancies in patients with myeloproliferative neoplasms: a population-based cohort study of 9379 patients. Leukemia. 2018; 32(10): 2203–2210.
- Langseth ØO, Myklebust TÅ, Johannesen TB, et al. Patterns of previous and secondary malignancies in patients with multiple myeloma. Eur J Haematol. 2021; 106(4): 529–536.
- Greenfield G, McMullin MF, Mills K. Molecular pathogenesis of the myeloproliferative neoplasms. J Hematol Oncol. 2021; 14(1): 103.
- Nangalia J, Green AR. Myeloproliferative neoplasms: from origins to outcomes. Blood. 2017; 130(23): 2475–2483.
- Passamonti F, Mora B. Myelofibrosis. Blood. 2023; 141(16): 1954–1970.
- Tefferi A, Lasho TL, Finke CM, et al. Targeted deep sequencing in primary myelofibrosis. Blood Adv. 2016; 1(2): 105–111.
- Hideshima T, Mitsiades C, Tonon G, et al. Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer. 2007; 7(8): 585–598.
- Hu J, Hu WX. Targeting signaling pathways in multiple myeloma: pathogenesis and implication for treatments. Cancer Lett. 2018; 414: 214–221.
- Lee H, McCulloch S, Mahe E, et al. Anti-myeloma potential of ruxolitinib in co-existing JAK2V617F-positive smouldering myeloma and polycythaemia vera. Br J Haematol. 2020; 189(3): e114–e118.
- Fiorini A, Farina G, Reddiconto G, et al. Screening of JAK2 V617F mutation in multiple myeloma. Leukemia. 2006; 20(10): 1912–1913.
- Castaneda O, Baz R. Multiple myeloma genomics — a concise review. Acta Med Acad. 2019; 48(1): 57–67.
- Cervantes F, Vannucchi AM, Kiladjian JJ, et al. COMFORT-II investigators. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013; 122(25): 4047–4053.
- Harrison CN, Vannucchi AM, Kiladjian JJ, et al. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016; 30(8): 1701–1707.
- Verstovsek S, Gotlib J, Mesa RA, et al. Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses. J Hematol Oncol. 2017; 10(1): 156.
- Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012; 366(9): 799–807.
- Santos FPS, Verstovsek S. JAK2 inhibitors for myelofibrosis: why are they effective in patients with and without JAK2V617F mutation? Anticancer Agents Med Chem. 2012; 12(9): 1098–1109.
- Quintás-Cardama A, Vaddi K, Liu P, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. 2010; 115(15): 3109–3117.
- de Oliveira MB, Fook-Alves VL, Eugenio AIP, 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: 206–215.
- Chen H, Sanchez E, Li M, et al. Anti-myeloma activity by the combination of the JAK2 inhibitor ruxolitinib with lenalidomide and corticosteroids. Blood. 2014; 124(21): 2114–2114.
- Berenson JR, Martinez D, Safaie T, et al. Ruxolitinib and methylprednisolone for treatment of patients with relapsed/refractory multiple myeloma. Br J Haematol. 2023; 200(6): 722–730.
- Chen H, Li M, Ng N, 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. 2021; 192(3): 568–576.
- Chen H, Li M, Sanchez E, et al. The JAK inhibitor blocks PD-L1, PD-L2 and CD44 expression in multiple myeloma (MM) and sensitizes MM cells to lenalidomide and steroids. Blood. 2018; 132(Suppl 1): 1910–1910.
- Chen H, Li M, Sanchez E, 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(2): 283–294.
- Ogiya D, Liu J, Ohguchi H, et al. The JAK-STAT pathway regulates CD38 on myeloma cells in the bone marrow microenvironment: therapeutic implications. Blood. 2020; 136(20): 2334–2345.