Alemtuzumab in the treatment of fludarabine refractory B-cell chronic lymphocytic leukemia (CLL)

Abstract

The introduction of immunotherapeutic agents has provided renewed hope for Chronic lymphocytic leukemia fludarabine-refractory patients. Several clinical trials have shown that alemtuzumab is a more effective option compared to combination chemotherapy for treatment of patients who have relapsed or who are refractory to fludarabine, including those with poor prognostic factors. Although there are significant potential toxicities associated with alemtuzumab, such as infusional reactions and the risk of cytomegalovirus (CMV) reactivation, most are manageable. Pre-treatment anti-pyretics and anti-histamines are recommended to prevent or mitigate the acute infusional reactions associated with intravenous infusion. Recent use of alemtuzumab via the subcutaneous route has been shown to be well tolerated and has yielded similar response rates to the infusional method of administration. Prophylaxis with thrimethoprim/sulphamethoxazole (TMP/SMZ) as well as valacyclovir or a similar anti-viral can prevent many of the opportunistic infections seen in early trials. Reactivation of CMV infection can be effectively managed with monitoring and early treatment. Chemo-immunotherapy combination with alemtuzumab has been tested and demonstrated unprecedented clinical results in relapsed and refractory patients. The use of this agent earlier in the algorithm of patients with these characteristics should be considered. Future areas of research will include the use of alemtuzumab in combination with other monoclonal antibodies and other targeted therapies.

Protocolo de Prevenção de Infeções Relacionadas com o Tratamento de Neoplasias Hematológicas

“…O anti-CD52 causa depleção linfocitária grave e prolongada (em alguns casos superior a um ano) na maioria dos doentes (a contagem mediana de CD4 + às quatro semanas de tratamento é de 0/mm 3 e seis meses após paragem do fármaco de 238/mm 3 ); causa também neutropenia profunda numa grande percentagem de doentes. 1,49 Deverá ser sempre feita profilaxia contra PPC e reativação de HSV/VZV. Nestes casos a profilaxia deverá ser mantida até pelo menos dois meses após paragem do anti--CD52 e recuperação imunológica com contagem de CD4 superior a 200/mm 3 .…”

Infections in Leukemia

“…Given the near ubiquitous expression of CD52 on immune cells, treatment results in the loss of circulating T cells, leading to defective cell mediated immunity and neutropenia in approximately 1/3 of patients. As a result, CMV reactivation occurs in 15 to 25% of patients and is the most commonly observed opportunistic infection (137,(143)(144)(145). Other infections include herpes simplex, varicella zoster, PJP, candidiasis, cryptococcosis, toxoplasmosis and mold infections(aspergillosis and mucormycosis) (17) It is recommended that all patients receiving alemtuzumab receive antiviral prophylaxis (acyclovir, valacyclovir or famciclovir).…”