Addition of granulocyte macrophage colony stimulating factor does not improve response to early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab

Abstract

Thirty-three previously untreated patients with high-risk chronic lymphocytic leukemia (CLL) were treated before meeting standard criteria with alemtuzumab and rituximab. Granulocyte macrophage colony stimulating factor (GM-CSF) was added to the regimen to determine whether it would improve treatment efficacy without increasing toxicity. High risk was defined as at least one of the following: 17p13−; 11q22.3−; unmutated IGHV (or use of VH3–21) together with elevated expression of ZAP-70 and/or CD38. Treatment was subcutaneous GM-CSF 250 μg Monday–Wednesday–Friday for 6 weeks from day 1, subcutaneous alemtuzumab 3 mg–10 mg–30 mg from day 3 and then 30 mg Monday–Wednesday–Friday for 4 weeks, and intravenous rituximab (375 mg/m2/week) for 4 weeks from day 8. Patients received standard supportive care and were monitored weekly for cytomegalovirus (CMV) reactivation. Using standard criteria, 31 (94%) patients responded to treatment, with nine (27%) complete responses (one with persistent cytopenia) and nine (27%) nodular partial responses. Median progression-free survival was 13.0 months and time to next treatment was 33.5 months. No patient died during treatment, seven (21%) had grade 3–4 toxicities attributable to treatment, and 10 (30%) had CMV viremia. Addition of GM-CSF to therapy with alemtuzumab and rituximab decreased treatment efficacy and increased the rate of CMV reactivation compared to a historical control.