Lumiliximab in combination with FCR for the treatment of relapsed chronic lymphocytic leukemia (CLL): results from a phase I/II multicenter study.

7003 Background: Lumiliximab is an anti-CD23 monoclonal antibody that is being investigated for the treatment of relapsed B-cell CLL (BCLL). CD23 is a glycoprotein expressed on the majority of CLL B cells. In a previous study, lumiliximab monotherapy given weekly was well tolerated, achieved sustainable CD23 receptor occupancy and showed clinical activity. A Phase I/II, multicenter study was conducted to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide, and rituximab (L + FCR) for patients (pts) with relapsed CD23+ BCLL. In addition, CD23 receptor occupancy on BCLL cells with L + FCR and possible effects of elevated serum CD23 were evaluated.,Thirty-one pts with relapsed BCLL received either 375 mg/m (n=3) or 500 mg/m (n=28) of L+ FCR for up to six 28-day cycles. All pts completed treatment and follow-up is ongoing. A semi-quantitative flow cytometry method was used to measure CD23 receptor occupancy and serum CD23 levels were measured using an enzyme-linked immunosorbent assay.,Median age at study entry was 58 yrs, 71% had Rai Stage I/II, and median # of prior regimens was 2 (1- 10). Using NCI-WG criteria, overall response rate was 65%: complete response (CR) 52% and partial response13%. Five of the 8 pts with del(11q22.3) achieved CR. Based on median follow-up of 16.8 mos (1.5 - 37.6), KM estimated median progression-free survival (PFS) for all pts was 19.3 mos. Median PFS for all responders and CR pts were 23.4 mos and 30.4 mos, respectively. Twenty-three pts (74%) reported a Grade 3 or 4 event, similar to what has been previously reported with FCR. L + FCR has a comparable safety profile with no additional toxicity. At lumiliximab schedule used, CD23 receptor occupancy was sustained with no effects by elevated levels of serum CD23.,These results suggest that L +FCR is an effective regimen for pts with relapsed B-CLL. L+FCR produced an impressive CR rate, an encouraging PFS and a similar safety profile to that of FCR. Monthly L + FCR achieved sustainable CD23 receptor occupancy on BCLL, which was not affected by elevated levels of serum CD23. A large, randomized, global study of L+ FCR vs FCR (LUCID) is ongoing to further evaluate the safety and efficacy of this regimen. [Table: see text].