Medline ® Abstract for Reference 115
of 'Treatment of relapsed or refractory chronic lymphocytic leukemia'
Lenalidomide and rituximab for the initial treatment of patients with chronic lymphocytic leukemia: a multicenter clinical-translational study from the chronic lymphocytic leukemia research consortium.
James DF, Werner L, Brown JR, Wierda WG, Barrientos JC, Castro JE, Greaves A, Johnson AJ, Rassenti LZ, Rai KR, Neuberg D, Kipps TJ
J Clin Oncol. 2014 Jul;32(19):2067-73. Epub 2014 May 27.
PURPOSE: Lenalidomide is an immunomodulatory agent with therapeutic activity in chronic lymphocytic leukemia (CLL). In preclinical models, lenalidomide acted synergistically with rituximab. The CLL Research Consortium initiated a phase II study to evaluate this combination in treatment-naive patients.
PATIENTS AND METHODS: Lenalidomide was initiated at 2.5 mg/day and was escalated based on treatment tolerability to a maximum of 10 mg/day, for 21 days/cycle, for a maximum of seven cycles. Rituximab was administered at the end of cycle 1 and was continued for seven cycles. Patients received allopurinol and aspirin for prophylaxis.
RESULTS: Sixty-nine patients enrolled onto one of two age-specific strata; patients' median age was 56 and 70 years for arms A and B, respectively. Patients in the older-patient stratum more frequently had elevated serum beta-2 microglobulin levels, high-risk Rai stage, and were less likely to complete the maximum planned therapy. Adverse events were similar in the two arms. Nonhematologic toxicity was predominantly at grade 1/2, and neutropenia was the most common hematologic adverse event. The response rate for arm A was 95%, with 20% complete responses (CRs) and 20% nodular partial responses. Of arm B patients, 78% achieved a response, of which 11% were CRs. Median progression-free survival (PFS) was 19 months for the younger cohort and 20 months for the older cohort.
CONCLUSION: 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 PFS did not differ.
Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.