Single-Agent Rituximab in Treatment-Refractory or Poor Prognosis Patients with Chronic Lymphocytic Leukemia.

Rituximab in combination with fludarabine and cyclophosphamide (R-FC) is the new standard therapy for patients with chronic lymphocytic leukemia (CLL). Rituximab in combination with FC or any other chemotherapy is indicated for first-line treatment of patients with CLL by the EMEA. However, the FC component of this treatment is myelosuppressive, and patients with CLL who refuse or are not candidates for myelosuppressive therapy have few treatment options. We investigated the effect of single-agent rituximab in patients with treatment-refractory or poor prognosis CLL.

23 patients with progressing CLL received single-agent rituximab at an initial weekly dose of 375 mg/m². Patients were progressively escalated to 3 g/m² at the fourth weekly dose and remained on this dose for the remainder of their treatment cycle. Clinical responses, adverse events and treatment history were recorded and analyzed. A patient with mantle cell variant CLL was included in this series but is omitted from the group analysis.

13 previously treated patients received a median of 1.5 (range 1–6) prior lines of therapy; 8 of these patients were fludarabine refractory. Nine patients had received no previous treatment for CLL. Overall response rate (ORR) and complete response (CR) rate were 90.9% and 54.5%, respectively. Even in patients who were fludarabine refractory ORR was 75% with 37.5% CR. Responses by population are summarized in table 1. As of August 2009, median progression-free survival (PFS) was 12.5 months (range 0-48), with a median response duration (DR) of 8.5 months (range 0-46) (fludarabine-refractory median PFS = 8 months). Patients with high-risk Binet stage C disease had less durable responses and shorter PFS compared with Binet stage A/B patients (DR= 8 vs. 9 months, PFS= 8 vs. 17 months). Patients ≥65 years had more durable responses and longer PFS compared with patients <65 years (DR= 11.5 vs. 5 months, PFS= 16 vs. 8 months). Four patients received rituximab as maintenance therapy (375mg/m² weekly for 4 weeks, every 6 months). All experienced CR or partial response (PR) and had a PFS which was considerably longer than the overall population (48, 36, 34 and 33 months); all 4 patients were still in remission as of August 2009. The patient with mantle cell variant CLL achieved a CR and is still in molecular remission with a DR of 94 months and PFS of 96 months as of August 2009. No unexpected adverse events were observed.

Single-agent rituximab was an effective treatment for treatment-refractory or poor prognosis CLL, and was well tolerated. High ORR and CR rates were seen even in patients who were fludarabine refractory. Encouraging responses were seen with rituximab maintenance and in older patients. These data suggest that there is a role for single-agent rituximab in the treatment of patients with difficult-to-treat CLL, and that the concept should be studied further.

Off Label Use: Rituximab is a monclonal antibody licenced for the treatment of NHL as a single-agent. Rituximab is CLL currently under review by the FDA as treatment for relapsed/refractory CLL in combination with chemotherapy. Here it is used as a single-agent treatment for CLL.