Chemoimmunotherapy with purine analogues and the CD20-antibody rituximab is the standard of care in younger and physically fit patients with chronic lymphocytic leukaemia (CLL). However, the majority of CLL patients are of advanced age and many of those are afflicted with comorbidity.

To date, there is no established standard treatment for such patients and the alkylating drug chlorambucil remains a valuable treatment option. The addition of CD20-antibodies (including the novel type II antibody GA101) to chlorambucil (CLB) has been proposed to improve alkylator-based therapy in CLL. Whether these regimens are beneficial in CLL patients with comorbidity remains to be explored.

A multicenter international 3-armed CLL trial comparing CLB alone with CLB plus rituximab (R-CLB) or GA101 (G-CLB) in comorbid CLL patients is currently underway.

Interim safety results in 6 elderly patients (aged 71-79 years) have so far shown that infusion-related reactions are common but are mild (grade 1-2) in all cases. NCI CTC grade 3 or 4 neutropenias were seen in 5 patients; 3 patients received G-CSF with immediate response. One patient had grade 3-4 thrombocytopenia while none of the patients developed grade 3-4 anaemia. No grade 3-4 infections were observed and there were no febrile neutropenias or infections in the presence of neutropenia requiring antibiotic therapy. All 6 patients showed rapid clearing of lymphocytes from their peripheral blood within a few days of first dosing with G-CLB.

These very early results indicate that chemoimmunotherapy with CLB and GA101 could be feasible in CLL patients of advanced age and with high burden of comorbidity. However, neutropenia as well as complications associated with comorbidity need special consideration in this very fragile patient population.

Reference

V Goede, K Fischer, B Raymonde et al Chemoimmunotherapy with Chlorambucil and the Type II CD20-Antibody GA101 In Patients with Chronic Lymphocytic Leukemia and Comorbidity: Results of the Run-In Phase of the CLL11 (BO21004) Trial Abstract 1387 presented at 52nd ASH, Orlando, FL, December 4-7, 2010.