ALBERT

Description: Background. Lenalidomide (Len) is an immunomodulatory drug with single agent activity in patients (pts) with treatment-naïve (TN) CLL, (overall response rate (ORR) 56-65%, Chen JCO 2011, Ferrajoli Blood 2011). Given the encouraging results of the combination of Len and rituximab (R) in relapsed CLL, we explored this combination as initial therapy. TN pts could derive greater benefit than relapsed pts from Len + R given their less compromised immune function. Methods. Fifty-eight pts were enrolled between 01/2012 and the present time. All patients had treatment indications per IWCLL 2008 criteria, WHO performance status ≤2 and adequate hepatic and renal function. Patients with HIV, hepatitis B or C infection were excluded. Treatment consisted of R 375 mg/m2 IV given weekly for 4 weeks then monthly during months (mo) 3-12 and Len 10 mg PO/day from day 9 for 24 mo. Allopurinol 300 mg PO daily was given for the first 2 weeks. No pts received antibiotic or DVT prophylaxis. Use of growth factors was allowed according to ASCO guidelines. Responses were assessed (2008 IWG criteria) at mo 3, 6 and every 6mo thereafter. Results. Forty-eight patients are evaluable for response and toxicity (8 too early, 1 lost to follow-up and 1 diagnosed with metastatic colonic adenocarcinoma within 1 week of study entry). Median age was 66 yrs (42-79). 29 (59%) pts were ≥age 65. 22 pts (46%) had Rai stage III-IV disease. Median β2M level was 3.8 mg/dL (1.4-10.5). 24/37 pts (65%) had unmutated IGHV gene and 31 pts (65%) expressed ZAP-70. 4 pts (8%) had del(17p) and 15 pts (32%) del(11q). Forty pts responded (ORR 83%). 7 pts (14.6%) achieved CR (1 MRD negative) and 33 (68.8%) achieved PR (including 7 nodular PRs). Median time to CR was 11mo (range 5-27). 5 pts discontinued therapy before the 3mo evaluation (4 due to toxicity and 1 due to unrelated co-morbidities). Six pts discontinued between 3 and 6mo (4 for refractory disease and 2 for toxicity after achieving PR). ORR was similar for patients with mutated and unmutated IGHV gene (85 vs 83%, p=0.96), age ≥65 and