Rituximab® and High Dose Methylprednisolone (HDMP) for the Treatment of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia.

High-dose gluocorticoids and the anti-CD20 mAb Rituximab each can effect partial responses in patients with chronic lymphocytic leukemia (CLL), although complete and durable responses to treatment with either of these agents have not been reported. We examined whether patients with relapsed and/or refractory CLL could respond to these agents when used in combination in a pilot clinical trial. Fourteen patients with progressive, symptomatic, and relapsed/refractory disease were treated with three four-week cycles of high-dose Methylprednisolone (HDMP) at 1gr/m2 daily for 5 days and weekly Rituximab® at 375mg/m2 for four weeks. The median age of the patients was 60 years, the male to female ratio was 4:1, the ECOG performance status was < 2, and the average number of prior treatments was 2. All patients failed or were intolerant to fludarabine and 86% had high-risk disease by the modified Rai classification. Sixty-five percent of the patients had CLL cells that expressed ZAP-70 and unmutated immunoglobulin variable region genes. Response assessment was performed at the end of each cycle, two months after completion of treatment, and each 3–6 months thereafter until the patients experienced disease progression and/or required further treatment. Objective responses were observed in all 14 patients, with 6 patients achieving a complete response (CR) and the remainder a partial response (PR) as per the NCI-working group criteria. We observed a significant decrease in peripheral white blood cell (WBC) counts, increase in hemoglobin, elevation of platelet counts and a dramatic decrease in lymphadenopathy and splenomegaly. Five of the treated patients have not required further treatment with a median follow up of 26 months. Of these 5 patients 3 have maintain a CR. The median time to progression (TTP) was 12 months. Overall, the treatment was well tolerated and all the patients, except one, completed 3 cycles of therapy. The majority of adverse events were Grade I-II (fluid retention, cough, transient hyperglycemia, fatigue). In addition, we observed 7 episodes of grade III-IV toxicity secondary to (anemia, CMV esophagitis and GI bleeding with one case each and two cases each of thrombocytopenia and neutropenia). These data suggest that treatment with the combination of Rituximab® and HDMP has increased activity over treatment with either agent alone and may produce durable complete responses in patients with refractory and / or relapsed CLL.