Lumiliximab

Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B‐cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open‐label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty‐seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression‐free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.

Recent advances in the treatment of chronic lymphocytic leukemia (CLL) have moved beyond the traditional use of alkylating agents and purine analogs into regimens combining these two chemotherapy classes with monoclonal antibodies.

This article reviews treatments options for patients with relapsed or refractory CLL.

Several studies have investigated novel agents in treating patients with 17p deletion, TP53 mutation, and fludarabine-refractory CLL, as well as patients with suboptimal response to intense treatment. These investigational agents include rituximab, alemtuzumab, ofatumumab, bendamustine, high-dose methylprednisolone, lenalidomide, lumiliximab, cyclin-dependent kinase inhibitors, small modular immunopharmaceuticals, Bcl-2 inhibitors, and histone deacetylase inhibitors. While these newer drugs and combination therapies have shown promise as treatment options for CLL, additional studies are needed to determine the immunosuppression, toxicities, and infections associated with their use.

Despite improvement in initial overall response rates, most patients relapse and require further treatment. CLL remains incurable with standard therapies due to development of disease refractoriness. As such, novel approaches such as those noted above warrant continued research to improve outcomes for patients with CLL.