Vol 14 (2023): Continuous Publishing
Case report
Published online: 2023-11-29

open access

Page views 715
Article views/downloads 359
Get Citation

Connect on Social Media

Connect on Social Media

Ruxolitinib as a primary treatment for multiple myeloma in a patient with primary myelofibrosis? A case report and the review of the literature

Przemysław Zygmunciak1, Justyna Iskrzak1, Joanna Góra-Tybor2, Ewa Lech-Marańda1, Bartosz Puła1
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.

Article available in PDF format

View PDF Download PDF file

References

  1. 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.
  2. 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.
  3. 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.
  4. Tefferi A. Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023; 98(5): 801–821.
  5. Genthon A, Killian M, Mertz P, et al. [Myelofibrosis: a review] [In French]. Rev Med Interne. 2021; 42(2): 101–109.
  6. Garmezy B, Schaefer JK, Mercer J, et al. A provider's guide to primary myelofibrosis: pathophysiology, diagnosis, and management. Blood Rev. 2021; 45: 100691.
  7. 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.
  8. 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.
  9. Tremblay D, Mascarenhas J. Next generation therapeutics for thetreatment of myelofibrosis. Cells. 2021; 10(5).
  10. 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.
  11. 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.
  12. Keenan C, Nichols KE, Albeituni S. Use of the JAK inhibitor ruxolitinib in the treatment of hemophagocytic lymphohistiocytosis. Front Immunol. 2021; 12: 614704.
  13. Levy G, Guglielmelli P, Langmuir P, et al. JAK inhibitors and COVID-19. J Immunother Cancer. 2022; 10(4).
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. Greenfield G, McMullin MF, Mills K. Molecular pathogenesis of the myeloproliferative neoplasms. J Hematol Oncol. 2021; 14(1): 103.
  22. Nangalia J, Green AR. Myeloproliferative neoplasms: from origins to outcomes. Blood. 2017; 130(23): 2475–2483.
  23. Passamonti F, Mora B. Myelofibrosis. Blood. 2023; 141(16): 1954–1970.
  24. Tefferi A, Lasho TL, Finke CM, et al. Targeted deep sequencing in primary myelofibrosis. Blood Adv. 2016; 1(2): 105–111.
  25. 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.
  26. Hu J, Hu WX. Targeting signaling pathways in multiple myeloma: pathogenesis and implication for treatments. Cancer Lett. 2018; 414: 214–221.
  27. 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.
  28. Fiorini A, Farina G, Reddiconto G, et al. Screening of JAK2 V617F mutation in multiple myeloma. Leukemia. 2006; 20(10): 1912–1913.
  29. Castaneda O, Baz R. Multiple myeloma genomics — a concise review. Acta Med Acad. 2019; 48(1): 57–67.
  30. 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.
  31. 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.
  32. 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.
  33. 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.
  34. 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.
  35. 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.
  36. 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.
  37. 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.
  38. 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.
  39. 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.
  40. 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.
  41. 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.
  42. 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.