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.

Table 1.

Overview of patients with MF/SS treated with alemtuzumab


Patient no.

Age/sex

Previous treatment

Best response

Cumulative alemtuzumab dose (mg)

Previous ANTH

Cardiac risks before alemtuzumab therapy

Cardiac toxicity during or after*alemtuzumab therapy
1   73/M   Steroids, interferon, Tigason   CR   1016   No   MI 1998, Asthma   None  
2   73/M   Methotrexate, interferon, photophoresis, chlorambucil, steroids, fludarabine ×5   PR   1033   No   Asthma, chronic bronchitis   None  
3   77/F   Methotrexate + 5FU ×9, PUVA   CR   913   No   HTN, CVL 1996   None  
4   60/F   PUVA, CdA ×4, CHOP ×8, radiotherapy   PD   563   Yes   None   None  
5   52/M   Chlorambucil + steroids, fludarabine + cyclophosphamide + steroids   SD   733   No   None   None  
6   61/M   PUVA-photophoresis, α-IFN, methotrexate   CR   1023   No   None   None  
7   49/F   Local skin treatment   PR   968   No   None   None  
8   65/F   Methotrexate, steroids   CR   334   No   Cardiomyopathy   None  
9   72/F   PUVA, radiotherapy   PR   1063   No   None   None  
10   55/M   PUVA, steroids   PR   1033   No   None   None  
11   63/M   CHOP ×5, radiotherapy   PD   373   Yes   None   None  
12   77/F   Radiotherapy, vitamin A, PUVA, α-IFN, methotrexate   SD   313   No   Angina pectoris   None  
13   62/F   PUVA, photophoresis, steroids   CR   876   No   None   None  
14   63/F   PUVA, α-IFN, chlorambucil + steroids   CR   1035   No   None   None  
15   60/F   Chlorambucil + steroids, CHOP ×4, photophoresis   PD   756   Yes   CHF, nonsymptomatic mitral insuffiency   None  
16   56/M   PUVA, radiotherapy   CR   1033   No   None   None  
17   71/F   PUVA, photophoresis   PR   1033   No   Unknown   None 
18   57/M   PUVA, steroids, methotrexate   PD   1033   No   None   None 
19   56/F   Radiotherapy, α-IFN, chlorambucil + steroids, methotrexate   PD   253   No   None   None  
20   49/M   CHOP, PUVA, radiotherapy, mustine   PD   613   Yes   None   None  
21   38/M   PUVA, α-IFN   SD   1009   No   None   None 
22   57/F   CHOP ×3, methotrexate   PD   805   Yes   HTN   None 
23   64/F   Steroids, CsA   CR   750   No   None   None  
24   54/F   Steroids, azathioprine, methotrexate, mycophenolate   CR   210   No   HTN   None  
25   57/F   Steroids, PUVA, extracorporeal phototherapy, chlorambucil   CR   720   No   None   None  
26   70/M   Steroids, PUVA   PR  360   No   HTN   None  
27   86/M   Steroids, PUVA   PR  300   No   None   None  
28   82/M   PUVA, chlorambucil, CsA, steroids   NR   100   No   None   None  
29   74/F   PUVA, DCF, steroids   NR   100   No   None   None  
30
 
60/F
 
PUVA, methotrexate, etoposide, CsA, DCF, steroids
 
PR
 
450
 
No
 
None
 
None
 

Patient no.

Age/sex

Previous treatment

Best response

Cumulative alemtuzumab dose (mg)

Previous ANTH

Cardiac risks before alemtuzumab therapy

Cardiac toxicity during or after*alemtuzumab therapy
1   73/M   Steroids, interferon, Tigason   CR   1016   No   MI 1998, Asthma   None  
2   73/M   Methotrexate, interferon, photophoresis, chlorambucil, steroids, fludarabine ×5   PR   1033   No   Asthma, chronic bronchitis   None  
3   77/F   Methotrexate + 5FU ×9, PUVA   CR   913   No   HTN, CVL 1996   None  
4   60/F   PUVA, CdA ×4, CHOP ×8, radiotherapy   PD   563   Yes   None   None  
5   52/M   Chlorambucil + steroids, fludarabine + cyclophosphamide + steroids   SD   733   No   None   None  
6   61/M   PUVA-photophoresis, α-IFN, methotrexate   CR   1023   No   None   None  
7   49/F   Local skin treatment   PR   968   No   None   None  
8   65/F   Methotrexate, steroids   CR   334   No   Cardiomyopathy   None  
9   72/F   PUVA, radiotherapy   PR   1063   No   None   None  
10   55/M   PUVA, steroids   PR   1033   No   None   None  
11   63/M   CHOP ×5, radiotherapy   PD   373   Yes   None   None  
12   77/F   Radiotherapy, vitamin A, PUVA, α-IFN, methotrexate   SD   313   No   Angina pectoris   None  
13   62/F   PUVA, photophoresis, steroids   CR   876   No   None   None  
14   63/F   PUVA, α-IFN, chlorambucil + steroids   CR   1035   No   None   None  
15   60/F   Chlorambucil + steroids, CHOP ×4, photophoresis   PD   756   Yes   CHF, nonsymptomatic mitral insuffiency   None  
16   56/M   PUVA, radiotherapy   CR   1033   No   None   None  
17   71/F   PUVA, photophoresis   PR   1033   No   Unknown   None 
18   57/M   PUVA, steroids, methotrexate   PD   1033   No   None   None 
19   56/F   Radiotherapy, α-IFN, chlorambucil + steroids, methotrexate   PD   253   No   None   None  
20   49/M   CHOP, PUVA, radiotherapy, mustine   PD   613   Yes   None   None  
21   38/M   PUVA, α-IFN   SD   1009   No   None   None 
22   57/F   CHOP ×3, methotrexate   PD   805   Yes   HTN   None 
23   64/F   Steroids, CsA   CR   750   No   None   None  
24   54/F   Steroids, azathioprine, methotrexate, mycophenolate   CR   210   No   HTN   None  
25   57/F   Steroids, PUVA, extracorporeal phototherapy, chlorambucil   CR   720   No   None   None  
26   70/M   Steroids, PUVA   PR  360   No   HTN   None  
27   86/M   Steroids, PUVA   PR  300   No   None   None  
28   82/M   PUVA, chlorambucil, CsA, steroids   NR   100   No   None   None  
29   74/F   PUVA, DCF, steroids   NR   100   No   None   None  
30
 
60/F
 
PUVA, methotrexate, etoposide, CsA, DCF, steroids
 
PR
 
450
 
No
 
None
 
None
 

M indicates male; F, female; PUVA, psoralen-ultraviolet light; 5FU, 5-fluorouracil; IFN, interferon; CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; CdA, 2-chlorodeoxyadenosine; CsA, cyclosporine A; DCF, deoxycoformycin; SD, stable disease; PR, partial response; CR, complete response; PD, progressive disease; CVL, cerebral vascular lesion; HTN, hypertension; CHF, congestive heart failure; ANTH, anthracyclines; MI, myocardial infarction.

*

Within 6 months of therapy

No event during alemtuzumab therapy; however, event after end of therapy is unknown

Resolution of symptoms, but persistent erythroderma and skin infiltrates

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.

1
Lenihan DJ, Alencar AJ, Yang D, et al. Cardiac toxicity of alemtuzumab in patients with mycosis fungoides/Sezary syndrome.
Blood
.
2004
;
104
:
655
-658.
2
Lundin J, Hagberg H, Repp R, et al. Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome.
Blood
.
2003
;
101
:
4267
-4272.
3
Enblad G, Hagberg H, Erlanson M, et al. A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas.
Blood
.
2004
;
103
:
2920
-2924.
4
Kennedy GA, Seymour JF, Wolf M, et al. Treatment of patients with advanced mycosis fungoides and Sezary syndrome with alemtuzumab.
Eur J Haematol.
2003
;
71
:
250
-256.