Severe Pulmonary Complication in Chemotherapy-Naive African-American Patient Following Bortezomib Therapy: a Case Report

Bortezomib is widely used to treat multiple myeloma (MM). It is also used in the management of recurrent, relapsed and chemotherapy-refractory other hematological malignancies. Bortezomib is considered to be a safe drug with manageable adverse side effects including peripheral neuropathy, thrombocytopenia and gastrointestinal symptoms. Rare but severe pulmonary complication has been reported in four Japanese and two African-American (AA) patients after bortezomib treatment for multiple myeloma refractory to multiple other regimens. To the best of our knowledge, this is the first case of chemotherapy-naïve AA patient who developed severe pulmonary complication after receiving bortezomib.

A 51-year-old AA female known for hypothyroidism, was diagnosed with IgG kappa MM after she presented with low back pain and was found to have a lytic lesion and compression fracture at the tenth thoracic vertebra. She was started on palliative radiation therapy to T5 to T12 (to a total of 2500 cGY). Four days after starting the radiation therapy, she received bortezomib (1.3 mg / m2) on days 1, 4, 8 and 11 combined with low dose dexamethasone (40 mg IV weekly). On day 12, she developed a dry cough, dyspnea and fever of 101.4 ⁰F. On physical examination, she had coarse crackles in all lung fields. Her white blood cell count remained within normal limit. Computed tomography of the chest with contrast identified new diffuse patchy opacities throughout the lung fields and small bilateral pleural effusions, but no evidence of pulmonary embolism. She became progressively hypoxic and was transferred to the Intensive Care Unit (ICU). Echocardiogram confirmed normal left ventricular function. She was subsequently intubated. Bronchoscopy was done, bronchioalveolar lavage failed to show any infectious organisms or malignancy, whereas transbronchial biopsy showed organizing pneumonia. The patient was treated with intravenous antibiotics and high dose steroid (methylprednisolone 1000mg/24hrs) for 3 days with rapid clinical improvement and was quickly weaned off the ventilator.

The incidence of serious side effects of bortezomib was reported to be less than 5%. Severe pulmonary complications after bortezomib treatment are particularly rare (Richardson PG et al, 2003). In 2006, Miyakoshi S. and colleagues described four Japanese patients who presented with severe pulmonary complication after bortezomib treatment. A genetic predisposition and previous auto peripheral blood stem cell transplant (PBSCT) have been attributed to the adverse effect seen exclusively in Japanese patients. Ohri, Boyer and their colleagues reported similar pulmonary complications in two African-American patients treated with bortezomib (Ohri A et al, 2006; Boyer JE et al, 2006). The clinical symptoms and radiological manifestations of our patient are similar to the previously reported African-American patients. However our case is chemotherapy-naïve whereas previously reported cases were pre-treated with various cytotoxic agents.

Our patient had transient fever, no leuckocytosis and negative blood and urine cultures; she also had a negative bronchoalveolar lavage, all argue against the possibility of infection. She had rapid improvement after high dose steroids, which support drug reaction rather than infection. Moreover, organizing pneumonia is a recognized type of drug-induced lung disease (Vahid B et al, 2008) and confirms the adverse event of bortezomib since our patient had no prior chemotherapies and was not on other medication at the time of event. Even if we admit the possibility of spillover effect from the limited field radiation the patient received, the extent of the lung parenchyma injury was far more conspicuous to be explained solely by radiation therapy alone.

This report reinforces the possibility of predictable manifestation of severe pulmonary complication due to bortezomib therapy in chemotherapy-naive African American patients. Clinicians should be aware of this potentially fatal complication and need to cautiously monitor their patients for early signs of respiratory problems. It also highlights the reversible nature of the pulmonary complication with high dose steroids. Patients who get radiation therapy to the chest while receiving bortezomib may need special attention.

No relevant conflicts of interest to declare.