SAN DIEGO, CA—Investigators at the 53rd American Society of Hematology Annual Meeting and Exposition presented study data demonstrating high response rates of lenalidomide and rituximab for the initial treatment of chronic lymphocytic leukemia (CLL). Danelle F. James, MD, from the Division of Hematology and Oncology, Moores Cancer Center, University of California, San Diego/UCSD, La Jolla, CA, and colleagues conducted the Phase 2, multicenter, two-stage study to evaluate the efficacy of combination therapy of lenalidomide and rituximab in CLL.

Lenalidomide is an immunomodulatory agent with therapeutic activity in CLL; rituximab, a CD20 mAb, has limited activity as monotherapy in CLL. In preclinical models, lenalidomide resulted in NK cell expansion and synergized with rituximab. To be eligible for the study, patients had to be treatment-naive, be indicated to receive therapy, have normal kidney function, and have no history of deep vein thrombosis or pulmonary embolism. Lenalidomide was administered on Days 1–21 (Cycle 1: 35 days, Cycle 2–7: 28 days) for seven cycles. Patients were initiated on lenalidomide 2.5mg/day. If the initial dose was tolerated, lenalidomide was escalated to 5mg/day on Day 8 of Cycle 1, and again to a maximum of 10mg/day on Day 1 of Cycle 3. Rituximab was administered at the following doses in Cycle 1: 50mg/m2 on Day 29, 325mg/m2 on Day 31, and 375mg/m2 on Day 33. During Cycle 2, rituximab 375mg/m2 was given weekly for four weeks, followed by monthly administration on Day 1 of Cycles 3–7. Concomitant medications included daily allopurinol 300mg and aspirin 81mg. 

Sixty-nine patients were enrolled and divided into Arm A (<65 years of age; n=40) and Arm B (≥65 years; n=29). Advanced Rai Stage III–IV disease was present in 14 patients (48%) in Arm B vs 10 (25%) in Arm A (P=0.04). At baseline, 29 patients (73%) in Arm A had an ECOG performance status of 0 compared with 10 patients (54%) in Arm B. Aggressive leukemia features, including unmutated IgVH genes and/or elevated CLL expression of ZAP-70, however, were more prevalent in Arm A. Del(17p) mutation was present in four Arm A and four Arm B patients; del(11q) was present in five Arm A and four Arm B patients. 

A larger proportion of patients completed all seven cycles in Arm A vs Arm B (35/40 vs. 16/27, respectively). However, investigators attribute this difference mainly due to toxicity. Toxicity was also a limiting factor to dose escalation or maintenance of the maximum 10mg lenalidomide dose in the older Arm B population. 

The overall response rate (ORR) to therapy was 95% (90% CI: 85–99) and 78% (90% CI: 61–90) for Arms A and B, respectively. Complete remission (CR) was achieved in 20% (90% CI: 10–33) and 7% (90% CI: 1–22) for both arms, respectively; nodular partial response (nPR) was achieved in 20% of patients in Arm A. Estimated median progression-free survival was 19 months for Arm A and 20 months for Arm B. Infusion and tumor flare reactions (TFR) were observed most frequently during Cycle 1. Serious Grade 3/4 adverse events were comparable between the two groups. Neutropenia was common and frequently Grade 3/4 in severity. Older patients were more likely to discontinue treatment early. The intra-patient dose-escalation schema was safe, with most patients reaching the maximum allowable dose for this study. 

Dr. James concluded that a seven-cycle course of lenalidomide and rituximab combination therapy demonstrated a high response rate as first-line treatment of CLL. He states, “Older patients were more likely to have advanced Rai stage at baseline and were less likely to escalate or maintain the maximum 10mg lenalidomide dose and/or complete the seven cycles of therapy, factors that may have contributed to a lower CR and ORR rate in Arm B.”