Cytokine efficiency in the treatment of high-grade malignant non-Hodgkin's lymphomas: results of a randomized double-blind placebo-controlled study with intensified COP-BLAM +/- rhGM-CSF.

In high-grade malignant non-Hodgkin's lymphomas (hNHL) recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was evaluated as support to chemotherapy. In a phase III trial, 172 patients (age 18-73 years, stage II-IV) were risk-stratified according to LDH levels and lymphoma size and randomized to receive rhGM-CSF (400 micrograms) (87 patients) or placebo (85 patients) subcutaneously days 8-14 of each cycle of an intensified COP-BLAM regimen. RhGM-CSF significantly reduced the length and nadir of neutropenia, the length of fever episodes, the frequency of all and of severe infections, and of hospitalization and antibiotic requirements. Complete response rates were 63% for all patients and 64% vs. 61% (n.s.) in the rhGM-CSF vs. the control group. Deviations from protocol in applied dosages of myelotoxic drugs and in cycle intervals maintained differed slightly in favor of the rhGM-CSF arm. However, there were no significant differences in overall survival between the GM-CSF treatment and control groups (21 vs. 23 months). Early relapse rates were markedly lower than in the standard-dose COP-BLAM/IMVP-16 regimen. Thus, GM-CSF abates toxic side effects of chemotherapy and may help to maintain dose intensity in high-risk hNHL.