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 resistanc e, and the presence of other concurrent diseases in this patient population . A phase I study was conducted to evaluate the toxicity of granulocyte mac rophage colony stimulating factor (GM-CSF) in myeloma patients as well as t he potential effect on the plasma cell labeling index (PCLI). Relapsed pati ents with multiple myeloma were eligible. Methods: The first phase of this trial assessed the toxicity (including the effect on disease progression) o f escalating doses (125-500 mug/m(2) 2 SC, days 1-5) of GMCSF, and the effe cts of this cytokine on PCLI. Patients whose PCLI doubled and increased to greater than or equal to1.7% were treated with chemotherapy including cyclo phosphamide, vincristine, prednisone, and GM-CSF. Twenty-two patients were enrolled. Results: The toxicity of GM-CSF was mild, and no dose-limiting si de effects were seen. Twenty-five percent of patients (5/20) achieved the t arget PCLI, and 4/5 proceeded to receive chemotherapy. No relationship of G M-CSF dose to increases of the PCLI was noted. All patients who received ch emotherapy responded. Conclusions: GM-CSF has acceptable toxicity in patien ts with multiple myeloma and produced increases of PCLI in selected individ uals. Further studies of GM-CSF alone or in combination with chemotherapy a re indicated.