GM-CSF safety and effects in the management of advanced/refractory multiple myeloma patients: a phase I trial.

Purpose: Some limitations of effective therapy in multiple myeloma include the low growth fraction of the malignant plasma cells, multi-drug resistance, and the presence of other concurrent diseases in this patient population. A phase I study was conducted to evaluate the toxicity of granulocyte macrophage colony stimulating factor (GM-CSF) in myeloma patients as well as the potential effect on the plasma cell labeling index (PCLI). Relapsed patients with multiple myeloma were eligible. Methods: The first phase of this trial assessed the toxicity (including the effect on disease progression) of escalating doses (125–500 μg/m2 SC, days 1–5) of GM-CSF, and the effects of this cytokine on PCLI. Patients whose PCLI doubled and increased to ≥1.7% were treated with chemotherapy including cyclophosphamide, vincristine, prednisone, and GM-CSF. Twenty-two patients were enrolled. Results: The toxicity of GM-CSF was mild, and no dose-limiting side effects were seen. Twenty-five percent of patients (5/20) achieved the target PCLI, and 4/5 proceeded to receive chemotherapy. No relationship of GM-CSF dose to increases of the PCLI was noted. All patients who received chemotherapy responded. Conclusions: GM-CSF has acceptable toxicity in patients with multiple myeloma and produced increases of PCLI in selected individuals. Further studies of GM-CSF alone or in combination with chemotherapy are indicated.