A combination of Granulocyte-macrophage colony-stimulating factor with the R2 regimen in elderly high-risk B cell lymphoma maintenance therapy improves survival by modulating natural killer cells

Abstract Background The clinical outcome of B-cell lymphoma has improved dramatically due to hematopoietic stem cell transplantation (HSCT) and biological agents. However, treatment of high-risk B cell lymphoma in the elderly remains a challenge because of their ineligibility for HSCT, high mortality and relapse rates. Maintenance therapy to improve the prognosis of B cell lymphoma in the elderly might be feasible. Methods We analyzed the efficacy of a combination of human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) with the R2 regimen in maintenance therapy in high-risk B cell lymphoma in the elderly of our center. A total of 83 elderly patients, who were ineligible for auto-HSCT and had a response after 6 cycles of induction therapy above a partial response, were divided into two groups: observation (n = 44) and R2 + GM-CSF (n = 39) by enrollment time. Results The clinical data, survival outcome, and the number of peripheral blood mononuclear cells were analyzed and compared. The numbers of lymphocytes (1.19 × 109/L vs. 1.03 × 109/L, P = 0.0062) and leukocyte (6.46 × 109/L vs. 4.85×109/L, P = 0.0048) increased after receipt of maintenance therapy, particularly the number of natural killer cells (0.131 × 109/L vs. 0.061 × 109/L, P = 0.0244). Patients receiving R2 + GM-CSF for maintenance had longer-term remission (duration of response (DOR): 18.9 months vs. 11.3 months, P = 0.001), and longer-term progression free survival (PFS) (not reached (NR) vs. 31.7 months, P = 0.037), and overall survival (OS) (NR vs. NR, P = 0.015). The new R2 regimen was safe and well tolerated. The elderly, high-risk, and high tumor burden seemed to have tendency to be independent prognostic factors for a better PFS (P = 0.060, 0.012, 0.005). Conclusions The new R2 regimen prolonged progression-free survival and overall survival among elderly patients with high-risk B cell lymphoma, appeared to lead to improve response without compromising its tolerability profile in elderly patients who are ineligible to receive HSCT. The number of patients in this trial was limited and the conclusions should be verified in larger, prospective, multicenter studies. Retrospectively registered: The ethical committee of Huadong Hospital (approval number: 2021K186).