Maintenance regimen of GM-CSF with rituximab and lenalidomide improves survival in high-risk B-cell lymphoma by modulating natural killer cells

Abstract

Background: The treatment of high-risk B-cell lymphoma (BCL) remains a challenge, especially in the elderly.

Methods: A total of 83 patients (median age 65 years), who have achieved a complete response after induction therapy, were divided into two groups: R² + GM-CSF regimen (lenalidomide, rituximab, granulocyte-macrophage colony-stimulating factor [GM-CSF]) as maintenance therapy (n = 39) and observation (n = 44). The efficacy of the R² + GM-CSF regimen as maintenance in patient with high-risk BCL was analyzed and compared with observation.

Results: The number of natural killer cells in patients increased after R² + GM-CSF regimen administration (0.131 × 10⁹ /L vs. 0.061 × 10⁹ /L, p = 0.0244). Patients receiving the R² + GM-CSF regimen as maintenance therapy had longer remission (duration of response: 18.9 vs. 11.3 months, p = 0.001), and longer progression-free survival (not reached (NR) vs. 31.7 months, p = 0.037), and overall survival (OS) (NR vs. NR, p = 0.015). The R² + GM-CSF regimen was safe and well tolerated. High international prognostic index score (p = 0.012), and high tumor burden (p = 0.005) appeared to be independent prognostic factors for worse PFS.

Conclusions: The maintenance therapy of R² + GM-CSF regimen may improve survival in high-risk BCL patients, which might be modulated by amplification of natural killer cells. The efficacy of the R² + GM-CSF maintenance regimen has to be further validated in prospective random clinical trials.

Keywords: B-cell lymphoma; lenalidomide; maintenance therapy; rhGM-CSF; rituximab.