Efficacy and Toxicity of Lenalidomide for Treatment of Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis

Background: During last decade, several therapeutic options have emerged for newly diagnosed (ND) or relapsed / refractory (RR) patients with chronic lymphocytic leukemia (CLL). Lenalidomide (Lena) has immunomodulatory, anti-angiogenic and antitumor activity. Lena is showing antitumor activity against CLL with durable responses.The main aim of our analysis is to study the published literature on the efficacy and safety of Lena based regimens in patients with ND and RR CLL. Methods: We performed the literature search (10/5/2019) using following databases (PubMed, Embase, Cochrane Library, Web of Science, and Clinical trials.gov) identified a total of 4835 articles. Following PRISMA guidelines, we selected twenty articles (Phase I/II/III) with a total of 1309 patients (pts) in which eleven articles (n= 914) were about ND CLL pts and nine articles (n=396) had pts with RR CLL. CMA software v.3 was used for meta-analysis. Results:1.Lenalidomide based regimens in previously untreated CLL Based on the pooled analysis,(table 1)(an overall response rate (ORR) of 59.9% (95% CI: 55.4-64.2) with complete response (CR) of 17.6% (95% CI: 8.9-31.8) is observed in previously untreated CLL and ORR of 57.6% (95% CI: 50.4-64.4) with a CR of 12.9% (95% CI: 7.7-20.8) in RR CLL were calculated. Most common grade (G) ≥3 adverse events (AE's) based on regimen were calculated using pooled analysis in CLL pts and results are given intable2. Lena in single drug regimen: Three studies (n=445) evaluated the efficacy of Lena as single agent (5mg-25mg). Subgroup pooled analysis showed an ORR of 56.4% (95% CI: 51.6-61) with CR of 7.3% (95% CI: 4.4-11.3). Pooled analysis for safety profile on most common G ≥3 AE's were neutropenia 72.2% (95% CI: 45.1-89.2), thrombocytopenia (tcp) 29.7% (95% CI: 9.1-64), anemia 0.8% (95% CI: 0.1-11.1), fatigue 3% (95% CI: 1.5-5.8) and infections 5% (95% CI: 1.22-18.7). Lena in two drug regimen: One study (n=69) evaluated the efficacy of Lenaas double regimen with ofatumumab. Sub-group pooled analysis showed an ORR of 88% (95% CI: 78-93.8) with CR of 16% (95% CI: 9.1-26.6). Best response was seen when Lena was used with Ofatumumab, with reported ORR of 71%. Pooled analysis for safety profile on most common G ≥3 AE's were neutropenia 58% (95% CI: 46.1-69), anemia 10% (95% CI: 4.8-19.6), tcp 3% (95% CI: 0.8-11) and fatigue 6% (95% CI: 2.3-14.7). Lena in three drug regimen: For six studies (n=375), a pooled analysis on Lena as three drug regimen calculated an