Originally published as JCO Early Release 10.1200/JCO.2004.07.060 on January 15 2004

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Selective CD4⁺ Lymphopenia in Melanoma Patients Treated With Temozolomide: A Toxicity With Therapeutic Implications

From the Clinical Immunology and Infectious Disease Services, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY

Address reprint requests to Paul B. Chapman, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; e-mail: chapmanp{at}mskcc.org

PURPOSE: Standard schedule temozolomide (TMZ; daily for 5 days every 4 weeks) is often used in melanoma patients, but phase III data show that it is no more effective than standard dacarbazine. Extended TMZ dosing regimens may be superior by delivering the drug continuously at a higher dose over time. Using an extended dosing schedule, we noted a high incidence of lymphopenia and occasional opportunistic infections (OIs). Here we report our retrospective experience in the first 97 patients.

MATERIALS AND METHODS: TMZ was administered at 75 mg/m²/d orally for 6 weeks every 8 weeks, although nine patients were treated continuously without a break. Seventeen patients were treated with TMZ alone; 73 patients received TMZ with thalidomide; seven patients received TMZ with low-dose interferon alfa.

RESULTS: Median duration of TMZ treatment was 113 days; 29% received 24 weeks of therapy. Lymphopenia was seen in 60% of patients (absolute lymphocyte count < 800/µL) with a median of 101 days to lymphopenia. TMZ did not cause significant neutropenia or thrombocytopenia. Lymphopenia was not more common in patients treated concomitantly with thalidomide. In all patients analyzed for lymphocyte subsets, lymphopenia induced by TMZ affected the CD4⁺ compartment preferentially. There were two documented OIs (Pneumocystis and Aspergillus pneumonia) as well as other infections indicative of T-cell dysfunction in another 21 patients.

CONCLUSION: TMZ at this dose and schedule results in CD4⁺ lymphopenia in a majority of patients that can result in OIs. Pneumocystis pneumonia prophylaxis should be considered for patients who develop sustained lymphopenia on TMZ.

Supported in part by NIH grants CA81293 and AI52239-01.

Presented in part in abstract form at the 38^th Annual Meeting of the American Society of Clinical Oncology, May 18-21, 2002, Orlando, FL and the 40^th Annual Meeting of the Infectious Diseases Society of America, October 24-27, 2002, Chicago IL.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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