International Journal of Hematology

, Volume 88, Issue 2, pp 219–222 | Cite as

Acute severe cardiac failure in a myeloma patient due to proteasome inhibitor bortezomib

  • Abdullah Hacihanefioglu
  • Pinar Tarkun
  • Emel Gonullu
Case Report


We present here a case of severe congestive cardiac failure, in a 47-year-old patient with myeloma who had no prior cardiac history, after receiving bortezomib. Bortezomib is a boron-containing molecule, which reversibly inhibits the proteasome, an intracellular organelle, which is central to the breakdown of ubiquitinated proteins and consequently crucial for normal cellular homeostasis. Phase II clinical trials demonstrate that it is effective for the treatment of relapsed refractory myeloma. Acute development of congestive cardiac failure associated with bortezomib therapy occurs very rarely or may be underestimated. Inhibition of proteasome activity may impair cardiac function due to accumulation of unfolded, damaged and undegraded proteins in myocytes. Patients with or without cardiac disease or previously received anthracycline-containing regimes should be closely monitored when being subjected to treatment with bortezomib.


Bortezomib Proteasome inhibitors Cardiac failure Myeloma 


  1. 1.
    Zolk O, Schenke C, Sarikas A. The ubiquitin–proteasome system: focus on the heart. Cardiovasc Res. 2006;70:410–21. doi: 10.1016/j.cardiores.2005.12.021.CrossRefPubMedGoogle Scholar
  2. 2.
    Goldberg AL. Protein degradation and protection against misfolded or damaged proteins. Nature. 2003;426:895–6. doi: 10.1038/nature02263.CrossRefPubMedGoogle Scholar
  3. 3.
    Hermann J, Ciechanover A, Lerman LO, Lerman A. The ubiquitin–proteasome system in cardiovascular disease: a hypothesis extended. Cardiovasc Res. 2004;1:11–21. doi: 10.1016/j.cardiores.2003.09.033.CrossRefGoogle Scholar
  4. 4.
    Vink J, Cloos J, Kaspers GJL. Proteasome inhibition as novel treatment strategy in leukemia. Br J Haematol. 2006;134:253–62. doi:10-1111/j.1315-2141.2006.06170.x.CrossRefPubMedGoogle Scholar
  5. 5.
    Adams J, Palombella VJ, Sausville EA, et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res. 1999;59:2615–22.PubMedGoogle Scholar
  6. 6.
    Almond JB, Cohen GM. The proteasome: a novel target for cancer chemotherapy. Leukemia. 2002;16:433–43. doi: 10.1038/sj.leu.2402417.CrossRefPubMedGoogle Scholar
  7. 7.
    Yu J, Tiwari S, Steiner P, Zhang L. Differentian apoptotic response to the proteasome inhibitor bortezomib [Velcade, PS-341] in Bax-deficient and p21 deficient colon cancer cells. Cancer Biol Ther. 2003;2:694–9.PubMedGoogle Scholar
  8. 8.
    Fujioka S, Schmidt C, Sclabas GM, et al. Stabilization of p53 in a novel mechanism for proapoptotic function of NF-kappa B. J Biol Chem. 2004;279:27549–59. doi: 10.1074/jbc.M313435200.CrossRefPubMedGoogle Scholar
  9. 9.
    Richardson PG, Mitsiades C, Schlossman R, Munshi N, Anderson K. New drugs for myeloma. Oncologist. 2007;12:664–89. doi: 10.1634/theoncologist.12-6-64.CrossRefPubMedGoogle Scholar
  10. 10.
    Voortman J, Giaccone G. Severe reversible cardiac failure after bortezomib treatment combined with chemotherapy in a non-small cell lung cancer patient: a case report. BMC Cancer. 2006;6:129. doi: 10.1186/1471-2407-6-129.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Suvannasankha A, Smith GG, Juliar BE, Abonour R. Weekly bortezomib/methylprednisolone is effective and well tolerated in relapsed multiple myeloma. Clin Lymphoma Myeloma. 2006;7:101–2.CrossRefGoogle Scholar
  12. 12.
    Suvannasankha A, Fausel C, Juliar BE, et al. Final report of toxicity and efficacy of a Phase II study of oral cyclophosphamide, thalidomide, and prednisone for patients with relapsed or refractory multiple myeloma: A Hoosier Oncology Group Trial, HEM01-21. Oncologist. 2007;12:99–106. doi: 10.1634/theoncologist.12-1-99.CrossRefPubMedGoogle Scholar
  13. 13.
    Orcivolo E, Buda G, Cecconi N, et al. Unexpected cardiotoxicity in haematological bortezomib treated patients. Br J Haematol. 2007;138:396–403. doi: 10.1111/j.1365-2141.2007.06659.x.CrossRefGoogle Scholar
  14. 14.
    Richardson PG, Hideshima T, Anderson KC. Bortezomib (PS_341): a novel, first class proteasome inhibitor for the treatment of multiple myeloma and other cancers. Cancer Control. 2003;10:361–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Powell SR. The ubiquitin–proteasome system in cardaic physiology and pathology. Am J Physiol Heart Circ Physiol. 2006;291:H1–19. doi: 10.1152/ajpheart.00062.2006.CrossRefPubMedGoogle Scholar
  16. 16.
    Willis MS, Patterson C. Into the heart: the emerging role of the ubiquitin–proteasome system. J Mol Cell Cardiol. 2006;41:567–79. doi: 10.1016/j.yjmcc.2006.07.015.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2008

Authors and Affiliations

  • Abdullah Hacihanefioglu
    • 1
  • Pinar Tarkun
    • 1
  • Emel Gonullu
    • 1
  1. 1.Faculty of Medicine, Department of HematologyKocaeli UniversityKocaeliTurkey

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