Treatment of Relapsed B-Cell Non-Hodgkin’s Lymphoma With a Combination of Chimeric Anti-CD20 Monoclonal Antibodies (Rituximab) and G-CSF: Final Report on Safety and Efficacy

March 1, 2001

Possible mechanisms of action of the chimeric CD20 monoclonal antibody rituximab (Rituxan) involve complement- and antibody-dependent cellular cytotoxicity (ADCC). Because granulocyte colony-stimulating factor (G-CSF [Neupogen])

Possible mechanisms of action of the chimeric CD20 monoclonalantibody rituximab (Rituxan) involve complement- and antibody-dependent cellularcytotoxicity (ADCC). Because granulocyte colony-stimulating factor (G-CSF[Neupogen]) greatly enhances the cytotoxicity of neutrophils in ADCC, theclinical efficacy of rituximab might be enhanced by the addition of G-CSF. In aphase I/II clinical trial we investigated the safety and efficacy of thecombination 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 priorsystemic therapies received a total of four weekly intravenous doses ofrituximab (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 ofrituximab and G-CSF. Adverse events occurred almost exclusively during the firstinfusion and mainly consisted of (grade I/II) fever, chills, and allergicreactions. Toxicity was comparable to toxicity as reported for rituximabmonotherapy.

Nineteen patients were evaluable for efficacy. The overallresponse rate was 42%(8/19; 95% confidence interval: 20%-67%). The percentages of completeremissions (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 medianfollow-up of 23 months. Only 1 patient who achieved a complete remission showedprogressive disease (after 18 months); the other 4 patients are still in CR (for13+, 24+, 25+, and 25+ months). In 4/5 patients that achieved a CR, remissionduration was already considerably longer than achieved on last previouschemotherapy. The duration of partial remissions appeared to be shorter: 4, 10,and 4+ months, respectively.

CONCLUSION: The combination of rituximab and G-CSF iswell-tolerated. Although the response rate seems comparable to that reportedfor rituximab monotherapy, remission duration in this small-sized phase II studyis remarkably long. Randomized comparison with rituximab monotherapy shouldsubstantiate this promising finding.

Click here to read Dr. Bruce Cheson's commentary on this abstract.