Rituximab as First-Line and Maintenance Therapy for Patients With Small Lymphocytic Lymphoma and Chronic Lymphocytic Leukemia

Although patients with small lymphocytic lymphoma and chronic lymphocyticleukemia (SLL/CLL) have CD20 expression on malignant lymphocytes, response rateswith standard rituximab (Rituxan) courses in refractory patients have been low.However, our initial experience with first-line therapy produced responses in 15of 23 patients with SLL. We have therefore expanded our experience, and have nowtreated a total of 68 previously untreated patients with either SLL (37patients) or CLL (31 patients) with single-agent rituximab.

All patients received rituximab (375 mg/m² weekly × 4); patients withobjective response or stable disease at reevaluation (6 weeks) continuedmaintenance courses of rituximab, using a standard 4-week schedule, every 6months for a maximum of four courses. Eligibility requirements included stageIII or IV SLL or CLL, no previous therapy, Eastern Cooperative Oncology Groupperformance status of 0 to 2, no life-threatening signs/symptoms, and informedconsent.

Between April 1998 and June 2001, 68 patients were treated in two sequentialmulticenter, community-based clinical trials; 66 have been evaluated fortreatment response. Patient characteristics included median age, 66 years(range: 38-89 years); B symptoms, 13 patients (23%); white blood cell count ³50,000 cells/mL, 19 patients (28%). At week 6, 33 of 66 evaluable patients (50%)had objective responses (9% complete response rate), and 32 additional patients(48%) had stable disease. Twenty-seven patients remain on therapy and arereceiving maintenance rituximab courses. Median follow-up of the initial 24patients is 26 months; in these patients, median progression-free survival was35 months. Toxicity with this treatment program was limited to the typicalrituximab-related infusion reactions; only one patient had reversible grade 3/4toxicity.

CONCLUSION: Rituximab is highly active as first-line therapy for CLL/SLL,producing substantially higher responses than have previously been seen inpatients with refractory disease. Further follow-up is necessary to assess theduration of response and the benefit of maintenance treatment with rituximab.Data correlating the response rate with surface CD20 antigen density will alsobe presented. Rituximab should be evaluated as part of first-line combinationtherapy for patients with CLL/SLL.