SAN DIEGO--New data on rituximab(Drug information on rituximab) (Rituxan), a chimeric anti-CD20 monoclonal antibody, show a projected median time to progression of 13 months among patients who responded to the drug (76 of 166 patients with relapsed or refractory indolent lymphoma). To date, nearly 70% of these patients (53) continue to respond to outpatient therapy with rituximab; only nine have died, all of progressive lymphoma.
Last year, rituximab became the first monoclonal antibody approved for the treatment of cancer when it received the FDAs nod for use as a single agent in patients with relapsed or refractory low-grade or follicular, CD20-positive B-cell non-Hodgkins lymphoma. The agent is given in four infusions over a 22-day period in an outpatient setting.
The current report of the pivotal trial, conducted at 31 US sites, provides data on the 166 intent-to-treat patients, with a median follow-up of 11.8 months (J Clin Oncol 16:2825-2833, 1998).
The results show a 48% overall response rate for rituximab as a single agent. "Most of the responses were partial (42%), which is typical of single-agent therapy in the setting of relapsed lymphoma," said Peter McLaughlin, MD, associate professor of medicine, M.D. Anderson Cancer Center, and lead author of the study. "These results are comparable to some of the most encouraging recent chemotherapy results for relapsed indolent lymphomas, such as with fludarabine [Fludara] or 2-chlorodeoxy-adenosine [cladribine, Leustatin]."
Among the responders to rituximab, the median duration of response to prior chemotherapy was 12 months, about equal to that seen with rituximab (13 months), although in the natural course of the disease, each subsequent remission usually is of shorter duration.
Toxicity Notably Mild
The researchers reported that toxicity "was notably mild, particularly with respect to myelosuppressive toxicities that are typical of standard chemotherapy or RIT [radioimmunotherapy]." The majority of adverse events occurred during the first infusion and were grade 1 or 2, with fever and chills the most common.
Only 12% of patients had grade 3 toxicities, and only 3% had grade 4 events. Human antichimeric antibody (HACA) was detected in only one patient and was not associated with any clinical or laboratory abnormalities. "By virtue of the modest toxicities of this agent, which do not overlap with the toxicities of standard chemotherapy, this agent lends itself to integration with chemotherapy programs," the investigators said.
Median serum antibody levels were higher for responders than for nonre-sponders. The researchers speculate that higher doses or more protracted dosing schedules might lead to higher antibody levels and, conceivably, higher response rates.
"These good response rates and time to progression data, along with the mild toxicity profile, suggest that rituximab as a single agent is an appropriate new treatment option for patients with relapsed indolent lymphoma," Dr. McLaughlin said. "It is also a very appealing agent to consider for further investigation, such as in an adjuvant role or in conjunction with chemotherapy."