Early Results Of a Phase II Study Of Lenalidomide and Rituximab As Frontline Treatment Of Patients With Chronic Lymphocytic Leukemia

The combination of lenalidomide and rituximab is an active treatment for patients (pts) with relapsed Chronic Lymphocytic Leukemia (CLL), with 66% Overall Response Rate (ORR) and a median Progression Free Survival (PFS) of 17.4 months (JCO 2013). We therefore sought to evaluate its efficacy and tolerability in untreated pts.

Twenty-five pts with untreated CLL have been enrolled. Rituximab (375 mg/m2 intravenously) was administered weekly during cycle 1 and on day 1 of cycles 3 to 12. Lenalidomide was started on day 9 of cycle 1 at 10 mg orally and administered daily continuously. Each cycle was 28 days. Rituximab was administered for 12 cycles; lenalidomide could continue indefinitely. Response was assessed every 3 cycles by 2008 NCI-WG criteria. Treatment-related toxicity was assessed using Common Terminology Criteria for Adverse Events (version 3.0). The primary end point of this study was ORR. Secondary objectives included PFS and Overall Survival (OS). PFS and OS were calculated using Kaplan-Meier estimates and compared using the log-rank test. Categorical variables were compared using Fisher's exact test (two tailed). Differences were considered significant if p≤.05.

Baseline characteristics of the 25 pts are shown in Table 1. Twenty-four pts are evaluable for toxicity (one pt was taken off study after only 7 days due to the diagnosis of widely metastatic pancreatic cancer) and 20 for response (2 pts too early, 3 pts early discontinuation). So far 5 pts received 1 cycle, 1 pt received 2 cycles, 6 pts received 3 cycles, 5 received up to 6 cycles and 8 received 12 or more cycles of therapy. ORR by 2008 NCI-WG criteria is 85%, including 2 (10%) complete remission (CR) and 15 (75%) partial remissions (PR). No significant association between ORR and baseline characteristics was observed. At the latest follow-up, the median dose of lenalidomide was 5 (2.5-10) mg and 14 (56%) pts needed at least one interruption because of toxicity. Grade 3-4 toxicities are summarized in Table 2. No episodes of grade 3-4 tumor flare were observed and 7 (29%) pts experienced a grade 1 or 2 tumor flare. Eight (32%) pts have so far discontinued treatment: 1 because of metastatic pancreatic cancer diagnosed after only 1 week on study, 2 because of progressive disease (after 4 months and 13 months), and 5 because of toxicity (skin rash in 3 pts, a deep venous thrombosis in 1 pt, and persistent neutropenia in 1 pt). Two of the 5 pts who discontinued treatment have required subsequent therapy. Twenty-four pts are alive, 1 pt died of metastatic pancreatic cancer after treatment discontinuation. At a median follow-up of 9 (1-17) months, median PFS and median OS have not been reached.

Our initial experience with the combination of lenalidomide and rituximab as front-line treatment of CLL indicates that this combination is tolerated by the majority of pts and responses are seen in 85% of them. Enrolment in this study is ongoing.

O'Brien:CELGENE: Consultancy. Ferrajoli:CELGENE: Research Funding.