Is Alemtuzumab Really the Single Active Agent for Treatment of Chronic Lymphocytic Leukemia?

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Journal of Clinical Oncology, Vol 26, No 35 (December 10), 2008: pp. 5827-a-5828

CORRESPONDENCE

Is Alemtuzumab Really the Single Active Agent for Treatment of Chronic

Lymphocytic Leukemia?

Satinderjit S. Oberoi, Rony M. Abou Jawde

Department of Hematology-Oncology, Heartland Regional Medical Center, Saint

ph, MO

To the Editor:

We read with great interest the article by Hillmen et al1 on first-line therapy

for chronic lymphocytic leukemia (CLL) and would like to commend the efforts of

the authors, but we have some queries and suggestions.

First, regarding patient selection and characteristics, two thirds of the

patient population who received alemtuzumab had early-stage (stage 1 or 2)

disease with no clear information about their symptoms. No bone marrow

examination was performed before the treatment and no computed tomography scans

were performed before enrollment onto the study. This can lead to understaging

of the patients involved in the study and potential overestimation of the

reported benefits of treatment.

Second, regarding follow-up evaluations, patients were evaluated by physical

examination, laboratory tests, and chest x-rays only. This is most likely

considered suboptimal in clinical practice, and can easily lead to

overestimation of the benefits of treatment. For example, while assessing

disease progression and response, no consideration would be given to

organomegaly and abdominal lymphadenopathy unless more imaging studies were

performed.

Third, regarding outcomes of the different treatments, the results of this study

show that alemtuzumab is superior to chlorambucil with regard to

progression-free survival (PFS). If we look at the study by Rai et al2 from

2000, PFS for chlorambucil was 14 months versus 20 months for fludarabine,

whereas in this study PFS for alemtuzumab was 14.6 months and 11.7 months for

chlorambucil. The median time to alternative therapy for alemtuzumab, according

to the current study is 23.3 months versus 14.7 months for chlorambucil. In the

study by Rai et al, the median time to alternative therapy was 27 months for

fludarabine versus 14 months for cholambucil. Although no comparisons should be

made across different studies, the reported outcomes seem to favor fludarabine

over alemtuzumab.

Complete remission rates were reported in 24.2% of patients with alemtuzumab

versus 2% with cholambucil. Byrd et al3 reported that 47% of patients with CLL

had complete remission with fludarabine and rituxan followed by rituxan alone.

This is almost twice the complete response rate reported in the current study.

In addition, alemtuzumab is not a benign chemotherapeutic agent, given that 15%

of patients had symptomatic cytomegalovirus and 52% of patients had asymptomatic

cytomegalovirus infections.

Therefore, the conclusion that alemtuzumab is the most active single agent for

the treatment of patients with CLL seems too ambitious, and the current

alemtuzumab regimen should be compared with studies using at least fludarabine

alone or fludarabine and rituxan as a comparative arm.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

NOTES

published online ahead of print at www.jco.org on November 10, 2008.

REFERENCES

1. Hillmen P, Skotnicki AB, Robak T, et al: Alemtuzumab compared with

chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin

Oncol 25:5616-5623, 2007

2. Rai KR, BL, Appelbaum FR, et al: Fludarabine compared with

chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med

343:1750-1757, 2000

3. Byrd JC, BL, on VA, et al: Randomized phase 2 study of

fludarabine with concurrent versus sequential treatment with rituximab in

symptomatic, untreated patients with B-cell chronic lymphocytic leukemia:

Results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood 101:6-14, 2003

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