Role of rituximab in first-line treatment of chronic lymphocytic leukemia

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BlankRole of rituximab in first-line treatment of chronic lymphocytic leukemia.

J and G Borthakur

Ther Clin Risk Manag, January 1, 2010; 7: 1-11.

Department of Leukemia, The University of Texas MD Cancer Center,

Houston, TX, USA.

Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous illness that

primarily afflicts the elderly. For many decades, the initial therapy for most

patients requiring treatment was limited to single-agent alkylator therapy.

Within the last two decades, we have seen remarkable progress in understanding

the biology of CLL and the development of more effective treatment strategies

that have employed monoclonal antibodies, such as rituximab (anti-CD20).

Furthermore, recognition of the synergy between fludarabine, cyclophosphamide,

and rituximab (FCR) prompted investigators to explore the clinical activity of

FCR in Phase II and III trials in patients with relapsed/refractory or

previously untreated CLL. On the basis of these findings, the US Food and Drug

Administration (FDA) recently approved rituximab in combination with fludarabine

and cyclophosphamide for the treatment of patients with relapsed/refractory or

previously untreated CD20-postive CLL. Recent data from a randomized Phase III

trial has confirmed improved overall survival with FCR in patients with

previously untreated CLL. However, FCR is not for everyone. More tolerable

regimens using rituximab for the elderly and less fit patients are being pursued

in clinical trials. Recent Phase II trials have explored potentially less

myelosuppressive approaches by using lower doses of fludarabine and

cyclophosphamide, replacing fludarabine with pentostatin, and combining

rituximab with chlorambucil. Furthermore new biomarkers predictive of early

disease progression have prompted investigators to explore the benefits of early

treatment with rituximab combined with other agents. In addition to the proven

utility of rituximab as a frontline agent for CLL, rituximab has a favorable

toxicity profile both as a single agent and in combination with chemotherapy.

The majority of adverse events are Grade 1 and 2 infusion-related reactions

(fevers, chills, and rigors) and occur with the first dose of rituximab. The

improved tolerability observed with second and subsequent infusions allows for

shorter infusion times. Rituximab's proven activity and favorable toxicity

profile has made it an ideal agent for expanding treatment options for patients

with CLL, the majority of whom are elderly.

PMID: 21339937