Lung Injury Associated with Bortezomib Therapy in Relapsed/Refractory Multiple Myeloma in Japan: A Questionnaire-Based Report from the “Lung Injury by Bortezomib” Joint Committee of the Japanese Society of Hematology and the Japanese Society of Clinical Hematology

Abstract

Bortezomib is a proteasome inhibitor that can be effective in the treatment of refractory and relapsed multiple myeloma. Recently, severe pulmonary complications associated with bortezomib therapy have been reported in Japan. Because bortezomib has not yet been approved for general use in Japan and is imported by attending physicians on the request of patients, The Japanese Society of Hematology and The Japanese Society of Clinical Hematology sent urgent questionnaires to the councilors of both societies to explore the situation and the details of pulmonary complications associated with bortezomib therapy. Clinical details were available for 46 patients who had been treated with personally imported bortezomib in Japan. Seven patients (15.2%), including 3 who died from respiratory failure, showed complications definitely or probably caused by bortezomib. Of the 7 patients, 6 had a prior history of stem cell transplantation (SCT), whereas only 14 of 39 patients without lung injury had received SCT treatment (P = .033, Fisher exact test). Multivariate analysis revealed that the concomitant use of corticosteroids might reduce the risk of lung injury (P = .024; odds ratio, 0.055) and that a previous SCT might increase the risk (P = .042; odds ratio, 13.140).We summarized these data from questionnaires for a limited Japanese cohort and therefore do not know the precise incidence of lung injury linked to fatal progression. Thus, future verification concerning this matter is warranted after the approval of bortezomib for use in Japan. Clinicians should be aware of the possibility of severe pulmonary complications associated with bortezomib therapy.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Bross PF, Kane R, Farrell AT, et al. Approval summary for borte-zomib for injection in the treatment of multiple myeloma. Clin Cancer Res. 2004;10:3954–3964.

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    Jagannath S, Durie BG, Wolf J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol. 2005;129:776–783.

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348:2609–2617.

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Jagannath S, Barlogie B, Berenson J, et al. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004;127:165–172.

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Miyakoshi S, Kami M, Yuji K, et al. Severe pulmonary complications in Japanese patients after bortezomib treatment for refractory multiple myeloma. Blood. 2006;107:3492–3494.

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352:2487–2498.

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    Danson S, Blackhall F, Hulse P, Ranson M. Interstitial lung disease in lung cancer: separating disease progression from treatment effects. Drug Saf. 2005;28:103–113.

    Article  PubMed  Google Scholar 

  8. 8.

    Inokuma S, Sakata M, Yoshida A, Shiratori K, Kiyosawa H. Bucillamine induced pulmonary injury occurs with immunoglobulin decrease. J Rheumatol. 1996;23:1282–1285.

    CAS  PubMed  Google Scholar 

  9. 9.

    Kamata Y, Anara H, Kamimura T, et al. Rheumatoid arthritis complicated with acute interstitial pneumonia induced by leflunomide as an adverse reaction. Intern Med. 2004;43:1201–1204.

    Article  PubMed  Google Scholar 

  10. 10.

    Park K, Goto K. A review of the benefit-risk profile of gefitinib in Asian patients with advanced non-small-cell lung cancer. Curr Med Res Opin. 2006;22:561–573.

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Verleden GM, du Bois RM, Bouros D, et al. Genetic predisposition and pathogenetic mechanisms of interstitial lung diseases of unknown origin. Eur Respir J. 2001;32(suppl):17s-29s.

    CAS  Google Scholar 

  12. 12.

    Chauhan D, Hideshima T, Anderson KC. Proteasome inhibition in multiple myeloma: therapeutic implication. Annu Rev Pharmacol Toxicol. 2005;45:465–476.

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Everhart MB, Han W, Sherrill TP, et al. Duration and intensity of NF-κB activity determine the severity of endotoxin-induced acute lung injury. J Immunol. 2006;176:4995–5005.

    CAS  PubMed  Google Scholar 

  14. 14.

    Tian XF, Yao JH, Li YH, et al. Effect of nuclear factor kappa B on intercellular adhesion molecule-1 expression and neutrophil infiltration in lung injury induced by intestinal ischemia/reperfusion in rats. World J Gastroenterol. 2006;12:388–392.

    CAS  PubMed  Google Scholar 

  15. 15.

    Yang G, Abate A, George AG, Weng YH, Dennery PA. Maturational differences in lung NF-κB activation and their role in tolerance to hyperoxia. J Clin Invest. 2004;114:669–678.

    CAS  PubMed  Google Scholar 

  16. 16.

    Franek WR, Morrow DM, Zhu H, et al. NF-κB protects lung epithelium against hyperoxia-induced nonapoptotic cell death-oncosis. Free Radic Biol Med. 2004;37:1670–1679.

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Oakervee HE, Popat R, Curry N, et al. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol. 2005;129:755–762.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Akihiko Gotoh or Kazuma Ohyashiki or Kazuo Oshimi or Noriko Usui or Tomomitsu Hotta or Kazuo Dan or Yasuo Ikeda.

About this article

Cite this article

Gotoh, A., Ohyashiki, K., Oshimi, K. et al. Lung Injury Associated with Bortezomib Therapy in Relapsed/Refractory Multiple Myeloma in Japan: A Questionnaire-Based Report from the “Lung Injury by Bortezomib” Joint Committee of the Japanese Society of Hematology and the Japanese Society of Clinical Hematology. Int J Hematol 84, 406–412 (2006). https://doi.org/10.1532/IJH97.06142

Download citation

Key words

  • Bortezomib
  • Lung injury
  • Stem cell transplantation
  • Corticosteroid