Rituximab Is Well Tolerated When Preceded by Chemo

NEW ORLEANS—Toxicity related to rituximab (Rituxan) is greatly reduced in patients with indolent lymphomas when the antibody is given after two cycles of mitoxantrone/cyclophosphamide chemotherapy, Christos Emmanouilides, MD, reported in a poster presentation at the 41st annual meeting of the American Society of Hematology (ASH).

Dr. Emmanouilides, of the University of California, Los Angeles, discussed data from an exploratory phase I/II study conducted there using this regimen in 24 patients with indolent B-cell lymphoma.

Patients were treated first with a cytoreductive regimen of cyclophosphamide and mitoxantrone (Novantrone), then by an immunotherapeutic regimen of rituximab and mitoxantrone (Table).

Cyclophosphamide/Mitoxantrone/Rituximab n Indolent NHL: Drug Dosage Schedule

Cytoreductive regimen

Cyclophosphamide 800 mg/m² day 1

Mitoxantrone 8 mg/m² day 1

Cycle repeats every 3 weeks for 2 cycles.

Immunotherapeutic regimen

Rituximab 375 mg/m² following cytoreduction

Mitoxantrone 8 mg/m² following cytoreduction

Cycle repeats every 2 weeks for 4 cycles.

“Rituximab, an anti-CD20 antibody, induces a 50% response rate in relapsed or refractory indolent lymphoma,” Dr. Emmanouilides said. “The efficacy of rituximab seems to be better in patients with less bulky disease. Also, growing in vitro and in vivo evidence suggests that rituximab may sensitize lymphoma cells to the effects of chemotherapy.”

The investigators’ hypotheses were that (1) satisfactory efficacy against indolent lymphoma might be achieved by combining rituximab with mild chemotherapy, (2) cytoreduction prior to administration of rituximab might enhance the rituximab antilymphoma effects, and (3) rituximab might be better tolerated by patients already cytoreduced by chemotherapy.

The regimen was quite well tolerated, he said. Only 2 of the 21 assessable patients had grade 1-2 infusion-related toxicity (one patient with rigors, and one with temperature of 37.9º C). Two rituximab infusions were briefly interrupted, but there were no discontin-uations. Grade 4 neutropenia occurred in 14 patients, and 7 of these patients were treated with GM-CSF.

Dr. Emmanouilides reported that there were no cases of neutropenic fever, grade 4 anemia or thrombocytopenia, grade 3-4 asthenia, congestive heart failure, or severe alopecia. There was one case of grade 2 alopecia, and there were three cases of grade 3 nausea after cyclophosphamide. There was one case of interstitial pneumonitis and one case of hypo-gammaglobulinemia, both in previously treated patients. No infections were noted in the trial.

Overall Response of 96%

Of 23 evaluable patients, 17 had a complete response, and 5 a partial response, for an overall response rate of 96%. Molecular remission occurred in 5 of 7 patients who were tested while in complete remission.

Complete or partial response occurred in all 13 patients with follicular lymphoma, in 4 of 5 patients with small-cell lymphocytic lymphoma, and in all 4 patients with lymphoplasmacytic lymphoma. One patient had failed cytoreduction. At a median follow-up of 8 months, two patients had developed progressive disease.

“Rituximab-related toxicity is nearly completely eliminated with this regimen,” Dr. Emmanouilides concluded. “Further follow-up is required to determine the long-term efficacy.”