Possible mechanisms of action of the chimeric CD20 monoclonal antibody rituximab(Drug information on rituximab) (Rituxan) involve complement- and antibody-dependent cellular cytotoxicity (ADCC). Because granulocyte colony-stimulating factor (G-CSF [Neupogen]) greatly enhances the cytotoxicity of neutrophils in ADCC, the clinical efficacy of rituximab might be enhanced by the addition of G-CSF. In a phase I/II clinical trial we investigated the safety and efficacy of the combination of rituximab and G-CSF in low-grade non-Hodgkin’s lymphoma (NHL) patients. Data on phase I have been reported before (Blood 92:4037a, 1998). Results of phase II will be presented.
Patients who had relapsed after a maximum of three prior systemic therapies received a total of four weekly intravenous doses of rituximab (375 mg/m2) in combination with a standard subcutaneous dose of G-CSF (5 µg/kg/d), administered for 3 days, starting 2 days before each infusion.
A total of 20 patients were treated with the combination of rituximab and G-CSF. Adverse events occurred almost exclusively during the first infusion and mainly consisted of (grade I/II) fever, chills, and allergic reactions. Toxicity was comparable to toxicity as reported for rituximab monotherapy.
Nineteen patients were evaluable for efficacy. The overall response rate was 42% (8/19; 95% confidence interval: 20%-67%). The percentages of complete remissions (CR) and partial remissions (PR) were 26% (5/19) and 16% (3/19), respectively. The median duration of response has not been reached at a median follow-up of 23 months. Only 1 patient who achieved a complete remission showed progressive disease (after 18 months); the other 4 patients are still in CR (for 13+, 24+, 25+, and 25+ months). In 4/5 patients that achieved a CR, remission duration was already considerably longer than achieved on last previous chemotherapy. The duration of partial remissions appeared to be shorter: 4, 10, and 4+ months, respectively.
CONCLUSION: The combination of rituximab and G-CSF is well-tolerated. Although the response rate seems comparable to that reported for rituximab monotherapy, remission duration in this small-sized phase II study is remarkably long. Randomized comparison with rituximab monotherapy should substantiate this promising finding.