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Rituximab, a New Advance in the Treatment of Non-Hodgkin Lymphoma

A better understanding of the immunology and molecular genetics of non-Hodgkin lymphoma has led to an improved classification system and continuing therapeutic advances, such as rituximab, with real clinical benefit, according to a recent review.

The International Lymphoma Study Group has developed a new system called the Revised European and American Classification of Lymphoid Neoplasms (REAL), which incorporates not only clinical features and morphology of the disease but also immunophenotype and genetics.

The age-adjusted international prognostic index (IPI) is now used to design therapeutic trials for patients with aggressive non-Hodgkin lymphoma (NHL) and in the selection of appropriate treatment approaches for individual patients," add Bryan T. Hennessy, MD, and colleagues, Department of Medical Oncology, St James Hospital, Dublin, Ireland.

"Rituximab is a human-mouse chimeric monoclonal anti-CD20 antibody that kills CD20-positive cells by activation of complement-dependent and antibody-dependent cell-mediated cytotoxicity," explain the researchers.

Rituximab holds promise for the treatment of follicular lymphoma. A response of 73% has been reported in asymptomatic previously untreated patients with follicular lymphoma.

Rituximab given as 4 once-a-week doses, resulted in a median time to progression of 552 days. "Approximately 50% of patients with relapsed or refractory follicular lymphoma respond to this 4-dose treatment regimen," report the researchers.

The addition of rituximab to chemotherapy for treatment of indolent lymphoma results in a response of up to 100%, with time to progression of more than 50 months.

A randomised trial has shown the effectiveness of rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) compared with CHOP alone, in elderly patients with diffuse large B-cell lymphoma, with an improvement in both response and survival.

"Addition of rituximab to chemotherapy might improve outcome for patients with mantle-cell lymphoma, a disease with the worst failure-free survival and overall survival of any type of NHL," write the authors.

Although the merits of available single agents can be debated, the maximum benefit from rituximab might be derived from its incorporation into first-line combination regimens such as fludarabine, cyclophosphamide, and rituximab.

Because of its excellent tolerability, rituximab is also useful in the first-line treatment of elderly patients with chronic lymphocytic leukaemia and in patients with poor performance status.

"Monoclonal antibodies engineered to target specific lymphoma antigens are central to current investigative efforts, and rituximab is an established treatment for both indolent and the aggressive B-cell NHL," the authors conclude.

Lancet Oncol 2004 Jun;5:6:341-53 "Non-Hodgkin lymphoma: an update"

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