Although strategies for the first-line treatment of chronic lymphocytic leukemia (CLL) are trending toward the use of ibrutinib or other kinase inhibitors, chemoimmunotherapy regimens combining rituximab with bendamustine or fludarabine and cyclophosphamide remain an important first-line approach for patients and yield durable responses for many. Relapse, however, is very common.
Results of the multinational CONTINUUM study (ClinicalTrials.gov Identifier: NCT00774345) suggest that maintenance therapy with lenalidomide is an effective way for prolonging progression-free survival (PFS) without affecting potential subsequent lines of therapy.1 Other studies confirm that lenalidomide may prolong remission.2,3
CONTINUUM enrolled patients with documented CLL who had received 2 lines of chemotherapy or chemoimmunotherapy and had reached at least a partial response (PR) in the second line. Patients (median age: 63 years) were randomly assigned to maintenance therapy with lenalidomide (160 patients) or placebo (154 patients). Lenalidomide 2.5 mg/day was initiated with escalation to 5 or 10 mg as tolerated, and continued until disease progression or unacceptable toxicity. The co-primary endpoints were PFS and overall survival (OS).
Maintenance lenalidomide reduced the risk of progression by 60% compared with placebo (hazard ratio, 0.40; 95% CI, 0.29-0.55; P <.0001), although no difference in OS was noted at follow up.
In a post-hoc subgroup analysis, PFS benefit was limited to patients who received the higher doses of lenalidomide. Researchers also assessed PFS2, which measures the time from randomization until disease progression after next-line treatment; 36% (56/157) of lenalidomide-treated and 58% (90/154) of placebo-treated patients received a subsequent line of therapy. The PFS2 benefit with lenalidomide vs placebo remained significant (hazard ratio, 0.46; (95% CI, 0.29-0.70; P = .0003).
In an accompanying editorial, Julie E. Chang, MD, of the University of Wisconsin in Madison, noted that inclusion of the PFS2 endpoint is an important strength of the study.4
“As we enter the era of [Bruton’s kinase inhibitor] therapies, it is important to realize that sequencing of therapeutics will occur,” said lead author Asher A. Chanan-Khan, MD, of the department of hematology/oncology at the Mayo Clinic in Jacksonville, Florida. “The fact that lenalidomide did not negatively affect the outcome of subsequent therapy is critical, as it demonstrates that patients effectively can be given the maintenance treatment with lenalidomide and physicians will not have to worry if such a strategy will compromise the use of subsequent treatment choices.”