Association Between Bortezomib and Cyclophosphamide with Interstitial Pneumonitis
Yes, both bortezomib (Velcade) and cyclophosphamide (Cytoxan) are associated with the development of interstitial pneumonitis, with cyclophosphamide specifically listed as causing this adverse effect in clinical guidelines.
Evidence for Cyclophosphamide-Induced Interstitial Pneumonitis
- Cyclophosphamide is explicitly listed in clinical guidelines as causing interstitial pneumonitis and pulmonary fibrosis among its adverse effects 1
- The American Heart Association specifically identifies interstitial pneumonitis as a known adverse effect of cyclophosphamide in their clinical guidelines 1
- Case reports document cyclophosphamide-induced acute respiratory distress syndrome leading to pulmonary fibrosis in as little as 30 days 2
- A case report of drug-induced interstitial lung disease caused by epirubicin and cyclophosphamide therapy showed diffuse ground-glass opacities and interlobular septal thickening consistent with hypersensitivity pneumonitis 3
- Ifosfamide, which is structurally similar to cyclophosphamide, has also been associated with fatal interstitial pneumonitis 4
Evidence for Bortezomib-Induced Interstitial Pneumonitis
- Case reports document bortezomib-induced pneumonitis in multiple myeloma patients, particularly during retreatment 5
- Bortezomib-induced pneumonitis typically presents with dyspnea, dry cough, and fever, with high-resolution CT showing bilateral infiltrates with ground glass appearance 5
- Pneumonitis can occur even when previous courses of bortezomib were administered without pulmonary complications 5
- The timing of bortezomib-induced pneumonitis is often relatively soon after administration, with one case reporting symptoms on the fifth day after the second dose 5
Management of Drug-Induced Pneumonitis
- For grade 1-2 pneumonitis, discontinue the suspected causative agent (bortezomib or cyclophosphamide) and initiate oral corticosteroids with prednisone 1 mg/kg daily or equivalent 6
- For grade 3-4 pneumonitis, hospitalize the patient, permanently discontinue the offending agent, and administer high-dose intravenous corticosteroids (methylprednisolone 2-4 mg/kg/day) 6
- Consider additional immunosuppressive strategies such as infliximab, mycophenolate mofetil, or cyclophosphamide if no improvement after 48 hours of steroid therapy 6
- Taper steroids slowly over 4-6 weeks after recovery to prevent recurrence 6
- Perform bronchoscopy with bronchoalveolar lavage to exclude infections, especially in grade 2 or higher pneumonitis 6
Risk Factors and Monitoring
- Prior pulmonary disease may increase risk of drug-induced pneumonitis 1
- Patients with preexisting lung diseases such as chronic obstructive pulmonary disease (COPD) or pulmonary fibrosis are at higher risk and diagnosis may be more challenging 1
- Monitor for symptoms including dyspnea, dry cough, and fever during treatment with either agent 5
- Consider baseline and periodic chest imaging in high-risk patients receiving these medications 6
Alternative Treatment Options
- In multiple myeloma patients who develop pneumonitis with bortezomib or cyclophosphamide, consider alternative agents such as lenalidomide, though this agent has also been associated with interstitial pneumonitis in rare cases 7
- Carfilzomib, a second-generation proteasome inhibitor, may be considered as an alternative to bortezomib, though it has its own toxicity profile including cardiotoxicity 1
- For patients with Waldenström's macroglobulinemia who develop pneumonitis with bortezomib-based regimens, ibrutinib may be an alternative option 1
Drug-induced pneumonitis is a serious adverse effect that requires prompt recognition and management. Clinicians should maintain a high index of suspicion when patients receiving bortezomib or cyclophosphamide develop respiratory symptoms, particularly dry cough, dyspnea, and fever.