A Study evaluating lenalidomide (Revlimid?, Celgene International S?rl), an oral immunomodulatory drug or IMiD [1], as consolidation therapy in patients with previously untreated chronic lymphocytic leukemia (CLL) reported that 91% of patients were still alive after a median follow-up of 21 Months. A Second study evaluating a combination of lenalidomide and rituximab (Rituxan?, Genentech, Inc/Roche Group), a monoclonal antibody, in Patients with relapsed/refractory CLL reported an overall response rate of 63%. Data from these studies was presented during the 52nd American Society of Hematology Annual Meeting in Orlando, Florida from December 4-7, 2010.

Chronic lymphocytic leukemia (CLL), the second most common type of leukemia , is a monoclonal B-cell malignancy that afflicts mainly older individuals. It often occurs during or after middle age and rarely occurs in children. Since many patients are diagnosed in the earliest stages, the course of the disease may be indolent and asymptomatic, requiring no therapy. These patients are generally closely monitored without treatment until symptoms appear or change. Patients who are diagnosed in advanced stages of the disorder or whose disease becomes symptomatic, treatment is required. Today, with the availability of new therapeutic agents and combination therapies showing great promise, the treatment and management of chronic lymphocytic leukemia is rapidly changing.

In the first study, 38 of 44 patients with previously untreated CLL received six cycles of pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2) and rituximab (375 mg/m2) (PCR) every 21 days. Following this treatment regimen, 34 patients continued to consolidation therapy with lenalidomide starting at 5 mg per day, escalating to 10 mg per day as tolerated for a median of seven cycles.

At a median follow-up of 21 months, 91% (40/44) of patients were still alive, and 21% (7/34) of patients who received at least one cycle of lenalidomide consolidation showed an improvement in the quality of their response, including three patients who converted from minimal residual disease (MRD)-positive to MRD-negative disease. The median duration of response has not been reached.

Additionally, a comparison of these data against historic PCR data showed the proportion of patients receiving consolidation who were free of retreatment at 12 months was 95% (42/44), compared to 86% (55/64) of patients without lenalidomide consolidation in the historic study.

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For patients receiving lenalidomide consolidation treatment in the study, the most common grade 3 or higher adverse events were neutropenia (grade 3, 41% 14/38; grade 4, 21% 7/38), leukopenia (grade 3, 32% 11/38), platelet count decrease (grade 3, 9% 3/38) and rash (grade 3, 6%, 2/38).

In the second study, 59 patients with relapsed/refractory CLL received rituximab 375 mg/m2 intravenously weekly for four weeks in cycle one, then once every four weeks during cycles three through 12. Oral lenalidomide 10 mg/day was started on day nine of cycle one on a continuous dosing schedule. Cycles were 28 days, with intention to continue therapy for 12 cycles or longer if the patient achieved a clinical response. Dose reductions were made following grade 3 or 4 lenalidomide-related adverse events, and allopurinol 300 mg daily was prescribed during the first two weeks as tumor lysis syndrome prophylaxis.

All 59 patients were evaluable for response, with evaluations performed after cycles three, six, and every six cycles thereafter. In the study, the overall response rate was 63% (37/59), with 5% (3/59) achieving a complete response. Additionally, 2% of patients (1/59) achieved a complete response with incomplete hematological recovery. 14% of patients (8/59) achieved nodular partial responses and 42% (25/59) achieved partial responses. Most responses (59%, 35/59) occurred within the first six cycles of therapy.

During the study, the highest incidences of grade 3/4 adverse events were neutropenia (68%, 40/59), thrombocytopenia (22%, 13/59) and anemia (10%, 6/59). Grade 3/4 infections occurred in 18 patients (31%), mostly in the upper respiratory tract. One patient experienced grade 3 tumor lysis syndrome. One treatment-related death occurred during the study due to ischemic stroke with infection.

These data are from an investigational study. Lenalidomide is not approved as a treatment for patients with chronic lymphocytic leukemia.

Rituximab is a monoclonal antibody which induces B-cell lysis through several mechanisms of action. [2] Rituximab is indicated for the treatment of previously untreated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC); relapsed refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent; previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy and non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy; Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens.

For more information:
[1] Full prescribing information lenalidomide (Revlimid?)
[2] Full prescribing information rituximab (Rituxan?)

Clinical trials
– Lenalidomide and Rituximab as Treatment of Chronic Lymphocytic Leukemia (NCT00759603);
– Multi-center Trial of Revlimid? and Rituximab for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) (NCT01199575);
– Multi-center Trial of Revlimid? and Rituximab, for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL) ( NCT00628238);
– Lenalidomide With or Without Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (NCT00096044)

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