Myocarditis During Lenalidomide Therapy

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BlankPublished Online, 28 September 2010, www.theannals.com, DOI

10.1345/aph.1P044.

Myocarditis During Lenalidomide Therapy

ph R Carver MD1*, Sunita Nasta MD2, Elise A Chong AB3, Mark Stonecypher MD

PhD4, E Wheeler MD5, Tahamtan Ahmadi MD6, J Schuster MD7

1 Clinical Professor, Lymphoma Program, Abramson Cancer Center; Heart and

Vascular Institute, University of Pennsylvania, Philadelphia, PA

2 Assistant Professor, Lymphoma Program, Abramson Cancer Center, University of

Pennsylvania

3 Research Assistant, Lymphoma Program, Abramson Cancer Center, University of

Pennsylvania

4 Resident, Department of Pathology and Laboratory Medicine, University of

Pennsylvania

5 Emeritus Professor, Department of Pathology and Laboratory Medicine,

University of Pennsylvania

6 Fellow, Lymphoma Program, Abramson Cancer Center, University of Pennsylvania

7 Associate Professor, Lymphoma Program, Abramson Cancer Center, University of

Pennsylvania

* To whom correspondence should be addressed. E-mail:

ph.carver2@... .

Abstract

OBJECTIVE: To report the first case of pathologically confirmed myocarditis in a

patient receiving treatment with lenalidomide for non-Hodgkin's lymphoma.

CASE SUMMARY: An 85-year-old woman with recurrent follicular lymphoma was

treated with lenalidomide 10 mg daily and low-dose dexamethasone 8 mg once

weekly in a clinical trial. She had a past medical history of hypertension and

breast cancer. Within 17 days of starting lenalidomide and dexamethasone, she

developed symptoms and signs of congestive heart failure. Despite aggressive

supportive care, she had progressive and refractory multiorgan failure and died.

Postmortem examination of the heart confirmed the absence of coronary artery

disease, and histopathological examination of the myocardium revealed a diffuse

lymphocytic/ eosinophilic inflammatory infiltrate with associated acute and

chronic myocardial injury affecting all 4 chambers of the heart, consistent with

myocarditis.

DISCUSSION: Lenalidomide is an immunomodulatory agent derived from thalidomide

and is approved for the treatment of multiple myeloma and myelodysplastic

syndromes. The efficacy of lenalidomide has been reported in B-cell

malignancies. Common toxicities are myelosuppression, fatigue, diarrhea, skin

rash, venous thromboembolism, peripheral neuropathy, and tumor flare reaction.

Cardiovascular toxicity has been limited to atrial fibrillation and an increased

risk for venous thromboembolism. Autoimmune hemolytic anemia, pneumonitis, and

dermatitis have been described with lenalidomide. We propose an immunological

mechanism for myocarditis based on the predominantly T-cell infiltration of the

myocardium.

CONCLUSIONS: Our findings suggest that lenalidomide may be a cause of

drug-induced myocarditis. When patients treated with lenalidomide present with

signs and symptoms of heart failure in the absence of other obvious causes,

lenalidomide hypersensitivity should be considered in the differential diagnosis

and a myocardial biopsy should be considered when other common causes of heart

failure have been excluded. A reasonable management approach is drug

discontinuation and early institution of corticosteroid therapy. An objective

causality assessment, using the Naranjo probability scale, revealed that the

adverse drug event was probable.

Reprints/Online Access: www.theannals.com/cgi/reprint/aph.1P044

Conflict of interest: Dr. Schuster receives support for research from Celgene

Corporation.