Rituximab ‘Surprisingly Active’ as First-Line or Maintenance Therapy for SLL and CLL

NASHVILLE, Tennessee—A pilot study of rituximab (Rituxan) as first-line therapy for small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) found an overall response rate of 56%, according to John Hainsworth, MD, director of clinical research at the Sarah Cannon Cancer Center in Nashville, Tennessee. Dr. Hainsworth discussed this work in a poster session at the 43rd Annual Meeting of the American Society of Hematology.

Although patients with SLL/CLL have CD20 expression on malignant lymphocytes, response rates with standard rituximab courses in refractory patients are only about 15%, compared to 60% in patients who have follicular non-Hodgkin’s lymphoma (NHL), Dr. Hainsworth reported.

"In a previous clinical trial performed in a multicenter, community-based setting, we treated 62 patients with indolent NHL (follicular and SLL histologies included) with first-line single-agent rituximab using a standard-dose 4-week schedule. Patients with initial response or stable disease received maintenance courses of rituximab at 6-month intervals. This produced responses in 15 of 24 patients with SLL (73%), with a median progression-free survival of 31 months. This was similar to results in patients with follicular NHL. We have therefore expanded our experience, and have now treated a total of 68 previously untreated patients with either SLL (37 patients) or CLL (31 patients) with single-agent rituximab," Dr. Hainsworth said.

Study Design

Rituximab was given at 375 mg/m² weekly by slow intravenous infusion for 4 weeks. Patients who had objective response or stable disease at the 6-week evaluation continued maintenance courses of rituximab, using a standard 4-week schedule, every 6 months, for a maximum of four courses. The study enrolled treatment-naive patients with stage III or IV SLL or CLL. Median age was 66 years (range: 48-89), 13 patients (23%) had B symptoms, and 19 patients (28%) had white blood counts above 50,000/µL.

Evaluation

At the first 6-week evaluation, 33 of 66 evaluable patients (50%) had objective responses (3% complete response rate), and 32 additional patients (48%) had stable disease. Complete responses continued to appear during the maintenance period (see Table 1). Current responses included complete remissions in 8% and partial remissions in 48%, for a response rate of 56%.

"Since 40% of patients are continuing maintenance rituximab, neither the final response rate nor the impact of maintenance therapy can currently be assessed. However, additional responses have been documented following maintenance therapy, and the overall response rate has already increased from 50% to 56%," Dr. Hainsworth said. "In our previous trial, overall response rate increased from 50% to 73% after all maintenance courses were completed."

Toxicity Is Limited

Toxicity with this treatment program was limited to the typical rituximab-related infusion reactions—only two patients had reversible grade 3/4 toxicity (one fatigue, one nausea/vomiting). None of the toxicities required hospitalization. The investigators reported that maintenance courses of rituximab, given at 6-month intervals, produce no cumulative toxicity and no increase in infections in patients with SLL/CLL.

"Rituximab is highly active as first-line therapy for CLL/SLL, producing substantially higher responses than previously seen in patients with refractory disease," Dr. Hainsworth said.

Dr. Hainsworth told Oncology News International that this study requires perhaps another year of follow-up before the duration of response and the benefit of maintenance rituximab can be assessed. "We know that rituximab is more active as first-line therapy than had previously been thought, and that it compares well with other first-line chemotherapy or antibody approaches," he said. "Rituximab should be evaluated as part of first-line combination therapy for patients with CLL/SLL."