First-Line Lenalidomide Plus Rituximab Is Safe and Effective in Older and Younger CLL Patients, Phase II Study Shows


Key Points

  • Most patients reached the maximum lenalidomide dose and achieved response.
  • Progression-free survival was 19 months in younger patients and 20 months in older patients.

The combination of lenalidomide (Revlimid) and rituximab (Rituxan) has shown synergistic activity in chronic lymphocytic leukemia (CLL) preclinical models. In a CLL Research Consortium phase II study of the combination in treatment-naive patients reported in the Journal of Clinical Oncology, James et al found that intrapatient dose-escalation of lenalidomide was safe and that the majority of older and younger patients reached the maximum lenalidomide dose and responded to combination treatment.

Study Details

In the study, 40 patients aged < 65 years (median, 56 years) and 29 aged ≥ 65 years (median, 70 years) received lenalidomide initiated at 2.5 mg/d and escalated based on tolerability to a maximum of 10 mg/d for 21 days per cycle for a maximum of seven cycles. After a test dose of rituximab 50 mg/m2, an additional 325 mg/m2 was administered on day 31 and another 375 mg/m2 was given on day 33. Rituximab was then continued at 375 mg/m2 weekly throughout cycle 2 and on day 1 of cycles 3 to 7. Patients received prophylactic allopurinol and aspirin.

Patients in the older group more frequently had elevated serum beta-2 microglobulin levels (55% vs 25% > 3.5 mg/L, P = .01) and high-risk Rai stage (III–IV in 48% vs 25%, P = .07) and were less likely to have Eastern Cooperative Oncology Group performance status of 0 (35% vs 73%, P = .01).

Dose Escalation

In total, 40% of younger patients and 21% of older patients were able to tolerate initial escalation of treatment doses. Most patients were able to have dose escalation at some point during study, resulting in a median dose of lenalidomide of the maximum allowed 10 mg/d in both groups. However, older patients were less likely to complete all seven cycles of therapy (59% vs 88%, P = .01).


Adverse events were similar in the two groups. The most common adverse events of any grade were tumor flare reaction (83%), fatigue (78%), and neutropenia (75%) in the younger patients and neutropenia (76%), anemia (72%), and fatigue (69%) in the older patients. The most common grade 3 or 4 adverse events were neutropenia (52.5% in younger patients and 66% in older patients), anemia (10% and 10%), and elevated transaminases (7.5% and 14%).


Objective response was achieved in 95% of younger patients, including complete response in 20% and nodular partial response in 20%, and in 78% of older patients, including complete response in 11%. Median progression-free survival was 19 months in the younger group and 20 months in the older group.

The investigators concluded, “Intrapatient dose-escalation was safe. The majority of patients reached the maximum lenalidomide dose and experienced a response to a defined seven-cycle course of lenalidomide and rituximab therapy. Despite differences in baseline characteristics and the response rate between the two strata, the [progression-free survival] did not differ.”

Thomas J. Kipps, MD, of University of California San Diego Moores Cancer Center, La Jolla, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by grants from the National Institutes of Health and American Society of Clinical Oncology Young Investigator Awards.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.