NEW ORLEANSToxicity 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
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
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
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.