(Chest. 2007; 131:1572-1574)
© 2007 American College of Chest Physicians
Hypersensitivity Pneumonitis-Like Syndrome Associated With the Use of Lenalidomide*
Aaron Thornburg, DO;
Rafat Abonour, MD;
Patricia Smith, BS;
Kenneth Knox, MD, FCCP and
Homer L. Twigg, III, MD, FCCP
* From the Divisions of Pulmonary, Allergy, Critical Care, and Occupational Medicine (Drs. Thornburg, Knox, and Twigg, and Ms. Smith) and Hematology and Oncology (Dr. Abonour), Indiana University Medical Center, Indianapolis, IN.
Correspondence to: Homer L. Twigg, III, MD, FCCP, Indiana University Medical Center, 1481 W Tenth St, VA 111P-IU, Indianapolis, IN 46202; e-mail: htwig{at}iupui.edu
 |
Abstract
|
|---|
Lenalidomide is an immunomodulatory agent approved for use in patients with myelodysplastic syndrome, and in combination with dexamethasone for refractory or relapsed multiple myeloma. Pulmonary toxicity is believed to be uncommon. In this report, we describe a patient receiving lenalidomide in whom dyspnea, fever, hypoxia, and diffuse pulmonary infiltrates developed. BAL demonstrated a significant lymphocytic alveolitis typical for hypersensitivity pneumonitis. Extensive workup for other causes, including infections, was negative. Finally, the patient had improvement in symptoms and oxygenation after withdrawing lenalidomide and recurrence of symptoms when the drug was restarted. Thus, the patient’s clinical course and workup strongly support a diagnosis of lenalidomide-induced hypersensitivity pneumonitis-like syndrome. Physicians should be cognizant of this potential complication in patients receiving thalidomide or thalidomide-like drugs who present with fever and pulmonary infiltrates and fail to improve despite treatment with broad-spectrum antibiotics.
Key Words: drug-induced lung disease • lenalidomide • pneumonitis
|
Introduction
|
|---|
Lenalidomide is the first of a new class of immunomodulatory agents that is chemically similar to thalidomide. It has been approved by the Food and Drug Administration for transfusion-dependent anemia due to low-risk or intermediate-risk myelodysplastic syndromes with a reported response rate of 56%.1 The drug is also approved in combination with dexamethasone as a treat-ment for patients with relapsed multiple myeloma, for whom the response rate is 30%.2 Lenalidomide has multiple immunologic effects, including T-cell activation, en-hanced activity of natural killer and natural killer T-cells, and inhibition of multiple cytokines, especially tumor necrosis factor-
.34 These immunologic effects induce apoptosis of myeloma cells, inhibit myeloma cell growth, inhibit angiogenesis, and reduce adhesion of myeloma cells to bone marrow.5
Reported side effects of lenalidomide include reduced platelet and neutrophil counts, diarrhea, fever, muscle cramps, neuropathy, constipation, rash, fatigue, and deep vein thrombosis. Pulmonary complications are believed to be uncommon. In this report, we describe a patient with dyspnea, fever, and diffuse pulmonary infiltrates while receiving lenalidomide and whose workup suggested hypersensitivity pneumonitis-like syndrome.
|
Case Report
|
|---|
The patient is a 60-year-old, white woman who received a diagnosis of multiple myeloma in December 2002. In April 2003, autologous stem cell transplantation was performed, resulting in complete remission until January 2005, when recurrence occurred. She was treated with IV bortezomib and cyclophosphamide with a good response until November 2005. At that time, she had disease progression; on November 30, 2005, oral lenalidomide and dexamethasone was started. Lenalidomide was dosed in cycles of 25 mg/d on days 1 to 21, followed by 7 days off. Dexamethasone was cycled at 40 mg/d on days 1–4, 9–12, and 17–20, followed by 7 days off. Treatment cycles were repeated every 28 days. No other changes were made in her medications. Lenalidomide was initially well tolerated and produced only minimal side effects of numbness and tingling in her lips that resolved when she was off the drug. However, 1 month prior to hospital admission, the patient began to have dyspnea that worsened with exertion, fatigue, fever, and chills resulting in admission to an outside hospital on January 24, 2006. At the time of hospital admission, she had completed two cycles of therapy with her last dose of lenalidomide and dexamethasone 7 days and 8 days previously, respectively. At the outside hospital, pneumonia was diagnosed and the patients was started on IV piperacillin-tazobactam and azithromycin. CT of the chest was performed and was concerning for an atypical or opportunistic infection, and she was transferred to Indiana University Medical Center on January 27, 2006, for further care.
Physical examination revealed an elderly white woman breathing comfortably at rest. She was afebrile. Room air oxygen saturation was 84% and increased to 96% with 2 L of oxygen. Chest examination revealed bibasilar dry crackles. Heart sounds were regular and without murmurs or gallops. The abdomen was soft and nontender, with no evidence of organomegaly. Neurologic examination revealed no focal deficits. Laboratory tests revealed a WBC count of 1,900/µL with 70% neutrophils; 17% lymphocytes; 9% monocytes; 3% eosinophils; hemoglobin, 10.2 g/dL; and platelet count, 202,000/µL. B-natriuretic peptide was 53 pg/mL. Chest radiograph showed low lung volumes, bronchovascular crowding, and basilar subsegmental atelectasis. Echocardiography demonstrated normal ejection fraction and normal valvular structures. Pulmonary function tests revealed moderate restriction (FVC, 2.00 L [63% predicted] and FEV1, 1.48 L [59% predicted]) and a diffusion capacity of 8.58 mL/min/mm Hg (33% predicted). Prior spirometry results in March 2003 had been normal: FVC, 3.11 L (97% predicted), and FEV1, 2.38 L (93% predicted). Blood and urine cultures were sent. She was treated with IV ceftazidime, azithromycin, and vancomycin for 4 days with minimal clinical improvement and remained hypoxic. All culture results were negative. A CT scan of the chest demonstrated ground-glass opacities (Fig 1
, top, A). Bronchoscopy with BAL and transbronchial biopsies was performed. Fluid was sent for bacterial, viral, fungal, acid-fast bacilli, and Legionella cultures, all of which came back negative. Transbronchial biopsies revealed nonspecific inflammation. However the BAL differential was highly abnormal, revealing 33% macrophages and 65% lymphocytes (Fig 2
). The high lymphocyte percentage was suggestive of a hypersensitivity-like pneumonitis. Flow cytometric analysis of the BAL lymphocyte population6 revealed 99% of the lymphocytes were CD3+ T-cells, with a CD4:CD8 ratio 0.61 (normal, 1.7 ± 1.0). Parenteral antibiotics were stopped, and the patient was discharged receiving oral cephalexin after a 7-day hospital stay. The patient did not receive corticosteroids during her hospital stay, nor was she discharged receiving on them. Prior to discharge, a home oxygen evaluation showed a resting room air blood gas pH of 7.46; PCO2, 37 mm Hg, PO2, 66 mm Hg, and oxygen saturation of 91%. She required 1 L of oxygen with exercise.
Received for publication July 25, 2006.
Accepted for publication October 10, 2006.
TOP
Abstract
Introduction
