Rituximab (Rituxan) may be an ideal agent for
combination with chemotherapy in patients with extensive indolent
lymphoma because of noncross-resistant efficacy and
differential toxicity. However, lethal complications have occurred.
Furthermore, the potential for synergy with chemotherapy has been documented.
A total of 24 patients with indolent B-cell non-Hodgkins
lymphoma (NHL) have been treated with a novel, three-drug
combination: cyclophosphamide (Cytoxan, Neosar), mitoxantrone
(Novantrone), and rituximab. Patient characteristics included: median
age, 60 years (range, 36 to 72 years); follicular histology, 13
patients; small lymphocytic lymphoma/chronic lymphocytic leukemia, 6
patients; lymphoplasmacytic, 4 patients; marginal zone, 1 patient.
All 24 patients had stage III or IV disease. Of the 24 patients, 10
had received prior treatment with one to three courses of
chemotherapy (including alkylating agents).
Patients first received cyclophosphamide, 800 mg/m², and
mitoxantrone, 8 mg/m² intravenously [IV] on day 1, every 3 weeks
for two cycles. Subsequently, patients received rituximab, 375
mg/m², followed by mitoxantrone, 8 mg/m², every 2 weeks for
four cycles. The regimen, particularly rituximab, was extremely well tolerated.
Only 2 of 22 assessable patients experienced grade 1 or 2
infusion-related toxicity (mild chills, fever of 37.9 °C, or
rash) during the first rituximab treatment (1 patient had received
rituximab previously). Grade 4 neutropenia was noted at some point in
14 patients, who were offered granulocyte-macrophage
colony-stimulating factor (GM-CSF [Leukine, Prokine]) support for
improvement of neutropenia and, possibly, enhancement of
antibody-dependent cellular cytotoxicity (ADCC). No infections were
noted. Alopecia was minimal.
Of 21 evaluable patients, 1 had a transient partial response (PR), 2
had a sustainable PR, and 17 achieved a complete response (CR) after
a median follow-up of 12 months. Hence, the overall response rate is
95%. The objective responses per subtype are: follicular, 11/11;
small lymphocytic lymphoma, 4/5; plasmacytic, 4/4; and marginal zone,
1/1. Except for two patients, all responders remain in remission.
Molecular remissions were noted in three of five tested patients.
CONCLUSION: We conclude that the
cyclophosphamide-mitoxantrone-rituximab regimen is effective and
extremely well tolerated. Furthermore, rituximab-related morbidity
has not been observed.