Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Twenty-seven cases of drug-induced interstitial lung disease associated with imatinib mesylate

Leukemia volume 20, pages 1162–1164 (2006)Cite this article

Imatinib mesylate (imatinib) is a potent inhibitor of the tyrosine kinase activity of ABL, c-kit, platelet-derived growth factor receptor and ABL-related gene (ARG). Selective blocking of the ABL-coded kinase activity provides significant clinical benefits in patients with chronic myelogenous leukemia (CML),1 and a selective inhibition of c-kit is also effective in patients with gastrointestinal stromal tumor (GIST). Imatinib was approved in Japan for the treatment of CML in November 2001 and for GIST in July 2003. Imatinib is generally well tolerated, and grade 3 and 4 non-hematologic toxicities are uncommon. Severe pulmonary adverse events of grade 3 and 4 were only 0.2 and 1.3% in early chronic phase CML, respectively. However, a considerable number of cases with interstitial lung disease (ILD) or interstitial pneumonia (IP) during imatinib therapy were recently reported spontaneously in Japan. Here, we focused on ILD as a possible adverse event associated with imatinib therapy.

We analyzed the adverse events associated with imatinib therapy in patients with CML or GIST, which physicians had spontaneously reported to Novartis Pharma KK, Tokyo, Japan. As of October 2003, approximately 5000 patients with CML and 500 patients with GIST are estimated to have been given imatinib since its approval in Japan, based on the amount of the drug shipment. Of 3023 adverse events spontaneously reported during imatinib therapy, 39 were cases of ILD, 27 cases of which were analyzed in this study after excluding apparent cases of fluid retention owing to imatinib, infection or lung disease induced by other causes. Chest radiographs and computed tomography (CT) or high-resolution CT images before and after the onset of drug-induced ILD were evaluated. Drug-related ILD was categorized into six radiological patterns in this study, namely, hypersensitivity reaction (HR) pattern, IP pattern, cryptogenic-organizing pneumonia (COP) pattern, nodular pattern, peribronchovascular bundle (PBVB) pattern and diffuse alveolar damage (DAD) patterns.2, 3

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Druker BJ, Talpaz M, Resta D, Peng B, Buchdunger E, Ford JM et al. Efficacy and safety of a specific inhibitor of the Bcr–Abl tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001; 344: 1031–1037.

    Article  CAS  Google Scholar 

  2. Rossi SE, Erasmus JJ, McAdams HP, Sporn TA, Goodman PC . Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics 2000; 20: 1245–1259.

    Article  CAS  Google Scholar 

  3. Sakai F, Noma S, Kurihara Y, Yamada H, Azuma A, Kudoh S et al. Leflunomide-related ILD: imaging features. Modern Rheumatol, in press.

  4. Bergeron A, Bergot E, Vilela G, Ades L, Devergie A, Esperou H et al. Hypersensitivity pneumonitis related to imatinib mesylate. J Clin Oncol 2002; 20: 4271–4272.

    Article  CAS  Google Scholar 

  5. Rosado MF, Donna E, Ahn YS . Challenging problems in advanced malignancy: case 3. Imatinib mesylate-induced interstitial pneumonitis. J Clin Oncol 2003; 78: 3171–3173.

    Article  Google Scholar 

  6. Ma CX, Hobday TJ, Jett JR . Imatinib mesylate-induced interstitial pneumonitis. Mayo Clin Proc 2003; 78: 1578–1579.

    Article  Google Scholar 

  7. Yokoyama T, Miyazawa K, Kurakawa E, Nagate A, Shimamoto T, Iwaya K et al. Interstitial pneumonia induced by imatinib mesylate: pathologic study demonstrates alveolar destruction and fibrosis with eosinophilic infiltration. Leukemia 2004; 18: 645–646.

    Article  CAS  Google Scholar 

  8. Isshiki I, Yamaguchi K, Okamoto S . Interstitial pneumonitis during imatinib therapy. Br J Haematol 2004; 125: 420.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Drs T Suda, K Chida, R Agatsuma, T Johkoh, S Noma and Y Kurihara for evaluation of chest radiographs and CT. We also thank the following investigators who participated in this study: A Yokohama, S Iida, A Miyata, T Murayama, Y Seki, T Kozuka, Y Shiga, S Hanada, K Yoshimoto, K Hirabayashi, M Inoue, N Kakazu, S Tonai, T Yagi, KImada, Y Okutani, M Fujita, T Mamiya, H Machishi, T Denda, T Yokoyama, H Ifuku, K Hatao, KYoshinaga, Y Iizuka, H Mihara, S Matsui, Y Masuda and K Tominaga.

Author information

Authors and Affiliations

  1. Division of Medical Oncology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan

    K Ohnishi

  2. Department of Radiology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan

    F Sakai

  3. Department of Respiratory Medicine, Nippon Medical School, Tokyo, Japan

    S Kudoh

  4. Aichi Cancer Center, Nagoya, Aichi, Japan

    R Ohno

Authors
  1. K Ohnishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Kudoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R Ohno
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K Ohnishi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ohnishi, K., Sakai, F., Kudoh, S. et al. Twenty-seven cases of drug-induced interstitial lung disease associated with imatinib mesylate. Leukemia 20, 1162–1164 (2006). https://doi.org/10.1038/sj.leu.2404207

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404207

This article is cited by

Search

Advanced search

Quick links