Early treatment of high risk chronic lymphocytic leukemia with alemtuzumab, rituximab and poly-(1-6)-beta-glucotriosyl-(1-3)- beta-glucopyranose beta-glucan is well tolerated and achieves high complete remission rates

Abstract

Poly-[1-6]-β-glucopyranosyl-[1-3]-β-glucopyranose (PGG) beta glucan is a Saccharomyces cerevisiae derived 1,3/1,6 glucose polymer with innate immune system activation potential. This phase I/II clinical trial enrolled 20 eligible patients with chronic lymphocytic leukemia with high-risk biological markers for early initial treatment with alemtuzumab, rituximab and PGG beta glucan (1-2-4 mg/kg/dose) over 31 days. PGG beta glucan at 4 mg/kg was well tolerated and used for the phase II study. There were three grade 3-4 toxicities at least possibly attributed to treatment. Nineteen (95%) patients responded to treatment with 13 (65%) complete responses. All patients were alive at a median follow-up of 24.4 months (range: 9.5-37). Eleven patients had progressive disease (median 17.6 months, 95% confidence interval [CI]: 9.7, 32.1) and eight patients were retreated (median 35.3 months, 95% CI: 17.9, not reached). We conclude that PGG beta glucan, alemtuzumab and rituximab treatment is tolerable and results in a high complete response rate.

Keywords: CLL; Chronic lymphocytic leukemia/small lymphocytic lymphoma; PGG beta glucan; alemtuzumab; high risk; rituximab.

Figure 1. Time to Progression

Nineteen patients responded to treatment and at a median follow-up duration of 24.4 months (range: 9.5 – 37), 11 have progressive disease as shown by this Kaplan-Meier survival curve.

Figure 2. Time to Retreatment

The Kaplan-Meier survival curves for time to treatment from three sequential phase II clinical trials using the same 5-week regimen of alemtuzumab and rituximab for early treatment of high risk CLL are plotted for comparison. MCO38G [3] used only alemtuzumab and rituximab (A+R) and enrolled 30 patients with a median time of follow up of 5.2 years (range 2.7–8.2). Twenty-four (80%) patients required retreatment for progressive CLL at a median time of 3.5 years (95% CI 2.1, 4.4). The subsequent trial MC0785 [4] added GM-CSF to the regimen (A+R+GM-CSF) and enrolled 33 patients with a median follow up of 5.0 years (range 3.9-5.6). Twenty-six (79%) of these patients have required retreatment at a median time of 2.9 years (95% CI 2.2, 3.8). The LS1084 study reported in this paper (A+R+ beta-glucan) enrolled 20 eligible patients with a median follow up of 2.0 years (range 0.8 – 3.1). Eight (40%) of these patients have required retreatment with a median time to retreatment of 2.9 years (range 1.5 to not reached).