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

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 CLL patients 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% 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.

Hypothesis: stimulation of trained immunity as adjunctive immunotherapy in cancer

“…Finally, these developments should lead to the identification of the most likely TI-based approaches for anticancer therapy, and these should be tested and validated in clinical trials. Promising combinations involving b-glucan are currently under clinical investigation, with trials investigating the synergistic effects of b-glucan and mAb against CD52 in chronic lymphatic leukemia showing promising results [82], and combinations of b-glucan and checkpoint inhibitors under way (NCT02981303 trial at ClinicalTrials.gov). More studies with b-glucan and also other inducers of TI are needed.…”

Imprime PGG-Mediated Anti-Cancer Immune Activation Requires Immune Complex Formation

“…Imprime has been well tolerated when administered intravenously to more than 300 cancer patients and has consistently shown compelling improvements in clinical response in multiple phase 2 clinical trials in combination with tumor-targeting or anti-angiogenic antibody therapies [1, 21]. In numerous preclinical tumor models, Imprime has repeatedly demonstrated anti-tumor efficacy in combination with tumor targeting, anti-angiogenic and immune checkpoint inhibitor antibodies [3–7].…”

“…In a randomized phase II trial, first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC) patients with Imprime plus bevacizumab, carboplatin and paclitaxel yielded an overall response rate of 60.4% and a median overall survival of 16.1 months versus 43.5% and 11.6 months in patients treated with bevacizumab, carboplatin and paclitaxel (unpublished data). In high-risk chronic lymphocytic leukemia patients (including those with del 17p, del 11q risk factors), the addition of Imprime to rituximab and alemtuzumab yielded a complete response rate of 65% vs a 37% complete response in an earlier study at the same institution with only rituximab and alemtuzumab [1, 2]. …”

A phase II randomized trial comparing standard and low dose rituximab combined with alemtuzumab as initial treatment of progressive chronic lymphocytic leukemia in older patients: a trial of the ECOG‐ACRIN cancer research group (E1908)

“…Combination therapy with alemtuzumab and rituximab achieved high response rates in phase II studies [6–10]. Although these response rates are higher than those previously reported for monotherapy with either mAb [6–11], there are no reported randomized studies showing conclusively that the addition of rituximab to alemtuzumab therapy in CLL patients improves outcome. However, the alemtuzumab and rituximab regimen was well tolerated and thus considered an option for non-chemotherapy initial treatment of elderly patients with progressive CLL.…”