OncoLink

Single-Agent Monoclonal Antibody Efficacy in Bulky Non-Hodgkin's Lymphoma: Results of a Phase II Trial of Rituximab

Davis TA, Levy R
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2001

Reviewers: John Han-Chih Chang, MD
Source: Journal of Clinical Oncology, 1999; Volume 17: Pages 1851-57

Background/Discussion/Critique

Rituximab (Rituxan trade name) is an antibody (Ab) that targets CD20. The CD20 antigen (Ag) is present exclusively on the surface of B cells, especially in B cell non-Hodgkin's lymphomas (NHL). The targeted cells are then destroyed by the body's immune system or are induced to undergo programmed cell death (apoptosis). Prior trials have found an overall response rate of nearly 50% with a great majority of them partial responders. Most were skeptical about the effectiveness of such an agent on bulky disease (> 10cm).

This trial was aimed at that type patient (bulky relapsed NHL). All were low grade of follicular B cell Non-Hodgkin's Lymphoma (NHL). CD20 positivity had to be demonstrated. Most (~ 70%) were stage III or IV. Median time from diagnosis was 4 years. No transformations seen in the patients evaluated.

The results demonstrated that very few had severe grade 3 - 4 toxicities (7%). The overall response rate was 43% with only 1 complete response and 11 partial responders. The time to response and duration of response is as indicated above. In this small population, histological type was the only subgroup to demonstrate a significant improvement in response: follicular small cleaved, follicular mixed and follicular large cell NHL (55%) versus small lymphocytic NHL (0/9). Some confounding factors leading to this result may have been present. First, median antibody concentration was higher in responders compared to nonresponders. The median antibody concentration was inversely associated with tumor bulk. It is conceivable that the small lymphocytic tumors were greater in bulk than the other types or that there is a mechanism by which this histological type of NHL can facilitate inactivation of this antibody. Greater efficacy in the nonresponders with increase of dosage per week or duration of treatment has lead to these results.

Rituximab is by no means a "home run" in salvage for patients with relapsed NHL. However, it has demonstrated significant promise even in bulky disease. Since severe toxicity were rare, further dose escalation may be possible. Studies are ongoing regarding combining Ab treatment with chemotherapy in definitive treatment. This may be the arena that this treatment becomes the most useful.