Case Reports: Monday, November 1, 2010 |

Recurrent Pneumonias and Squamous Cell Carcinomas of the Skin During Treatment With Mepolizumab in a Patient With Hypereosinophilic Syndrome FREE TO VIEW

Cyrus Shariat, MD; Dina Abi Fadel, MD; Gail Schattner, MD
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New York University, New York, NY

Chest. 2010;138(4_MeetingAbstracts):15A. doi:10.1378/chest.10725
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INTRODUCTION: We report the case of a patient with hypereosinophilic syndrome (HES) who experienced initial clinical improvement on mepolizumbab. Development of recurrent pneumonias and squamous cell carcinomas of the skin while receiving mepolizumab led to discontinuation of the drug.

CASE PRESENTATION: A 46 year old man with a history of asthma presented with worsening dyspnea and wheezing in October 2004. Medical history included atopic dermatitis and eosinophilic gastroenteritis. A complete blood count demonstrated 4500 eosinophils. Chest CT scan showed no significant infiltrates or bronchiectasis. He was initiated on systemic steroids. ANCA studies were negative and a bone marrow biopsy showed no malignancy. Attempts to decrease prednisone led to worsening asthma and increasing eosinophilia. In September 2005, he was enrolled in a trial of mepolizumab for treatment of HES. After receiving three monthly doses, eosinophil count decreased to zero and asthma symptoms improved. Prednisone was discontinued. By 2007, eosinophil counts rose to 3000 and he suffered multiple asthma exacerbations requiring prednisone. In 2008, he resumed mepolizumab, administered for compassionate use. Asthma symptoms improved, eosinophil counts decreased to < 100 and prednisone was discontinued. In December 2008, he developed left lower lobe pneumonia. Two months later, he developed right upper lobe pneumonia. Sputum grew Haemophilus influenza. The following month, he again developed fever, cough and pneumonia with growth of Streptococcus pneumoniae. He had 3 additional episodes of pneumonia in 2009, all which resolved with antibiotics. Subsequently, multiple sputum cultures grew mycobacterium avium. Throughout 2009, he also developed eight squamous cell carcinomas of the skin. Because of concerns of recurrent infection and skin cancer, mepolizumab was discontinued.

DISCUSSIONS: Hypereosinophilic syndrome (HES) is a rare group of disorders characterized by overproduction of eosinophils, end-organ eosinophilic infiltration and injury with no identifiable cause. Forty percent of patients with HES develop pulmonary disease. The primary goal of treatment of HES is to reduce eosinophil-mediated end-organ damage. For most patients, high dose corticosteroids remain first line therapy. Second line agents include interferon-alpha, hydroxyurea and vincristine. IL-5 is the major cytokine responsible for eosinophil maturation and function. Mepolizumab, an anti-IL-5 antibody, is currently only available in clinical trials or for compassionate use. In a recent study, patients with steroid-controlled HES were randomized to receive placebo or mepolizumab. Compared to placebo, significantly more patients receiving mepolizumab achieved a reduction in prednisone dose to < 10mg/day, with almost 50% becoming corticosteroid-free. In another study, mepolizumbab reduced exacerbations and eosinophil levels in patients with refractory eosinophilic asthma. Questions that remain regarding the use of mepolizumbab include long-term safety, patient selection and duration of effect after discontinuation. An open-label extension study is ongoing to address these issues. In the original study, there were no differences in the rates of pneumonia between treatment and placebo groups. With regard to malignancy, one patient in the extension study developed angioimmunoblastic lymphoma which was thought to be related to mepolizumab. The patient described in this case discontinued mepolizumab because of the temporal correlation between starting the drug and the occurrence of frequent pneumonias and skin squamous cell carcinomas. Whether these events were related to treatment is unknown. Long-term follow-up from ongoing trials and reporting by physicians caring for patients on mepolizumab may help to answer these questions.

CONCLUSION: Mepolizumab has shown promising results in clinical trials in the treatment of HES. Compassionate use should be considered in patients who are refractory to standard treatment. However, further follow-up studies are required to determine its long-term safety.

DISCLOSURE: Cyrus Shariat, No Financial Disclosure Information; No Product/Research Disclosure Information

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RothenbergME et al.2008; Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumbab.NEJM358,1215–1228. [CrossRef] [PubMed]
PranabashisH et al.2009; Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma.NEJM260,973–983.




RothenbergME et al.2008; Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumbab.NEJM358,1215–1228. [CrossRef] [PubMed]
PranabashisH et al.2009; Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma.NEJM260,973–983.
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