No cardiac toxicity associated with alemtuzumab therapy for mycosis fungoides/Sézary syndrome

We read with interest the article from Lenihan et al.¹  In this report, 4 of 8 patients with mycosis fungoides/Sézary syndrome (MF/SS) were reported to have developed either congestive heart failure or cardiac arrhythmia during alemtuzumab (Mab-Campath, Campath; Schering, Berlin, Germany) treatment. None had a history of cardiac problems, and cardiotoxicity during therapy was considerably improved after discontinuation, suggesting a link with alemtuzumab. They suggest that the cardiotoxicity might be explained by cytokine release or direct effects on the heart.

We therefore rechecked the individual files of 30 patients with advanced MF/SS who had participated in European trials of alemtuzumab. A complete physical examination and electrocardiogram (ECG) were performed at baseline. Physical re-examination was performed regularly during and after treatment. ECG was repeated if there were clinical signs of cardiac disease. Based on these analyses, we cannot confirm the findings of Lenihan's study.¹  In a phase 2 trial of 22 patients with MF/SS,²  there was no clinical cardiac toxicity during or after alemtuzumab treatment. Similar to the study by Lenihan,¹  alemtuzumab was administered intravenously on 3 consecutive days at doses (3 mg, 10 mg, and 30 mg), followed by 30 mg 3 times weekly for up to 12 weeks. The overall response rate was 55%; 32% complete remissions and 23% partial remissions. Median cumulative alemtuzumab dose was 913 mg (range 253 mg-1063 mg) compared with 30 mg to 553 mg in Lenihan's study. There were 7 of 22 patients who were considered to have pre-existing cardiac risk (previous myocardial infarction, n = 1; hypertension, n = 4; cardiomyopathy, n = 1; angina pectoris, n = 1; congestive heart failure/mitral insufficiency, n = 1). There were 5 patients who had received prior doxorubicin; the median cumulative dose was 408 mg (range, 255 mg-680 mg). No clinical cardiotoxicity occurred during or after alemtuzumab therapy in these patients. In contrast, all 3 patients in Lenihan's study who developed heart failure had received prior doxorubicin.

A retrospective analysis of 8 individual MF/SS patient files from similar studies within the United Kingdom confirmed our findings. All except 1 patient had received prior chemotherapy and/or radiotherapy. Collectively, our data on 30 patients (Table 1) receiving alemtuzumab for advanced MF/SS indicate that clinical cardiotoxicity appears to be rare.

Furthermore, alemtuzumab therapy of T-cell prolymphocytic leukemia and peripheral T-cell lymphoma has not been associated with cardiotoxicities and, therefore, it seems unlikely that release of T-cell cytokines is a cause of significant cardiac toxicity.^2-4  It remains unclear why the patients with MF/SS in Lenihan's study¹  developed cardiac complications.