Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
glass vials containing 30 mg/mL
Approved indication: chronic lymphocytic leukaemia
Australian Medicines Handbook section 14.3.4
The treatment of chronic lymphocytic leukaemia is changing with increasing use of multidrug regimens including fludarabine (see 'Treatment of adult leukaemias', Aust Prescr 2006;29:76-9). Although response rates have improved, some patients do not respond and in others the disease progresses within a few months. The median survival for these patients with refractory disease is only eight months.
Alemtuzumab is a humanised monoclonal antibody that has been studied in chronic lymphocytic leukaemia because it binds to a glycoprotein (CD52) on the surface of lymphocytes. By binding to this antigen alemtuzumab induces lysis of the cell.
In a phase II study, 29 patients with relapsed or refractory disease were given intravenous infusions of alemtuzumab three times a week for up to 12 weeks. Although adverse reactions were common, 11 patients had a partial response and one had a complete response to alemtuzumab.1
Another phase II study enrolled 24 patients who had previously been treated with fludarabine. There were no complete responses, but eight patients had a partial response. Overall, median survival was approximately 28 months, but in the responders it was 36 months.
A larger study included 93 patients in whom previous treatment including fludarabine had failed. The aim was to give patients infusions of alemtuzumab three times a week for up to 12 weeks. This regimen resulted in two patients having a complete response and 29 having a partial response. Overall median survival was 16 months. Approximately 10% of the patients died during the study or within 30 days of treatment.3
The infusions of alemtuzumab are given over two hours. The pharmacokinetics of alemtuzumab are not linear as clearance declines during treatment. At the start of treatment the mean half-life is eight hours, but increases to six days.
The dose of the infusion has to be increased gradually as alemtuzumab may be poorly tolerated. Infusion-related reactions include fever, hypotension and gastrointestinal upsets. Nearly 90% of patients have rigors. There have been fatal cardiovascular adverse events. Premedication with steroids, an analgesic and an antihistamine is recommended.
Most patients will develop a cytopenia.3 Transfusions of blood or platelets may be needed.
The action of alemtuzumab means that infections are common 4and can be fatal. They include pneumonia, and viral and fungal infections. Antibiotic prophylaxis may reduce the risk of pneumocystis pneumonia.
Although alemtuzumab has a clinical benefit for some patients3, its role will be limited by its toxicity. At present it is only approved for use after at least two other therapies have failed.
The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
Notes on references
At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).
At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).
- Osterborg A, Dyer MJS, Bunjes D, Pangalis GA, Bastion Y, Catovsky D, et al. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. J Clin Oncol 1997;15:1567-74.
- Rai KR, Freter CE, Mercier RJ, Cooper MR, Mitchell BS, Stadtmauer EA, et al. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol 2002;20:3891-7.
- Keating MJ, Flinn I, Jain V, Binet J-L, Hillman P, Byrd J, et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood 2002;99:3554-61.
- Thursky KA, Worth LJ, Seymour JF, Prince HM, Slavin MA. Spectrum of infection, risk and recommendations for prophylaxis and screening among patients with lymphoproliferative disorders treated with alemtuzumab. Br J Haematol 2005;132:3-12.