Fatal interstitial lung disease induced by rituximab-containing chemotherapy, treatment with TNF-α antagonist and cytokine profiling: a case-report and review of the literature

J Clin Pharm Ther. 2013 Jun;38(3):249-53. doi: 10.1111/jcpt.12052. Epub 2013 Mar 18.

Abstract

What is known and objective: Rituximab, an anti-CD20 monoclonal antibody, is widely used with good response for the treatment of B-cell lymphoma and various refractory autoimmune diseases. Although rituximab is effective, rare but serious pulmonary adverse reactions have been reported. We report on a case of rituximab-induced life-threatening interstitial lung disease in a patient with diffuse large B-cell lymphoma (DLBCL), and describe the patient's serum cytokine profile during anti-TNF-α treatment.

Case summary: A 71-year-old woman diagnosed with DLBCL was treated with three cycles of rituximab-containing chemotherapy. She developed a fatal respiratory failure, which was eventually diagnosed as rituximab-induced interstitial lung disease (R-ILD). The R-ILD in this patient did not respond to intensive steroid treatment, or to enternacept, an anti-TNF therapy. During therapy, we observed that the serum level of IL-6 was much higher at the beginning of treatment than was usual for other DLBCL patients. Levels of IL-6 and TNF-α also increased during the course of the clinical exacerbation. We undertook a literature search and reviewed similar cases of R-ILD.

What is new and conclusion: Although rituximab is generally effective and safe, caution is required for high-risk patients, as in our case, and as reported in several other cases in the literature. Cytokine analysis may help in identifying patients at high risk of R-ILD. Better intensive therapeutic approaches other than steroids are required even during the early stages of the complication.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Murine-Derived / adverse effects*
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Cytokines / metabolism
  • Fatal Outcome
  • Female
  • Humans
  • Lung Diseases, Interstitial / chemically induced*
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / metabolism
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Rituximab
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Rituximab