Randomized, Double-Blind, Placebo-Controlled, Phase III Study of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor as Adjunct to Induction Treatment of High-Grade Malignant Non-Hodgkin's Lymphomas

• Published in: Blood 1993-10, Vol.82 (8), p.2329-2339
• Main Authors: Gerhartz, Heinrich H., Engelhard, Marianne, Meusers, Peter, Brittinger, Gunter, Wilmanns, Wolfgang, Schlimok, Gunther, Mueller, Peter, Huhn, Dieter, Musch, Reinhard, Siegert, Wolfgang, Gerhartz, Diana, Hartlapp, Joachim H., Thiel, Eckhard, Huber, Christoph, Peschl, Christian, Spann, Wolfgang, Emmerich, Bertold, Schadek, Christine, Westerhausen, Martin, Pees, Hans-Wilhelm, Radtke, Hartmut, Engert, Andreas, Terhardt, Elke, Schick, Hans, Binder, Thomas, Fuchs, Roland, Hasford, Jorg, Brandmaier, Roland, Stern, Angelika C., Jones, Thomas C., Ehrlich, Hartmut J., Stein, Harald, Parwaresch, Mohamed, Tiemann, Markus, Lennert, Karl
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antibodies - blood; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bacterial Infections - prevention & control; Bleomycin - administration & dosage; Cyclophosphamide - administration & dosage; Double-Blind Method; Doxorubicin - administration & dosage; Female; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; Humans; Lymphoma, Non-Hodgkin - blood; Lymphoma, Non-Hodgkin - drug therapy; Lymphoma, Non-Hodgkin - mortality; Male; Middle Aged; Platelet Count - drug effects; Prednisone - administration & dosage; Procarbazine - administration & dosage; Recombinant Proteins - therapeutic use; Survival Rate; Vincristine - administration & dosage
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V82.8.2329.2329

We evaluated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; Sandoz Pharma [Basel, Switzerland]/Schering-Plough [Kenil-worth, NJ]) as an adjunct to a modified (mainly cyclophosphamide and doxorubicine increased 1.5-fold) COP-BLAM regimen in the primary treatment of high-grade malignant non-Hodgkin's lymphomas (NHL). Patients (n = 182; stage ll-IV; age, 15 to 73 years) were randomized to rhGM-CSF (400 μg) or placebo for 7 days subcutaneously after chemotherapy. Efficacy was analyzed for patients receiving at least 70% of study medication (n = 125). The frequency of clinically relevant infection was reduced by rhGM-CSF (28 v 69 infections, 16 v 30 patients, P = .02) with a cumulative probability of remaining infection free in 70% versus 48% (P = .05 log rank test at 190 days). Periods of neutropenia (P = .01 in 5 of 6 courses), days with fever (2.1 v 4.0, P = .04) and days of hospitalization for infection (3.5 v 8.0 days, P = .01) were significantly reduced. Complete response (CR) rates, assessed by prognostic risk, were 15 of 19 (79%) in treated versus 20 of 21 (95%) in controls in the low-risk group (P = .12). In the high-risk group, 31 of 45 (69%) treated patients achieved CR versus 25 of 52 (48%) of controls (P = .04). No difference in survival has been seen after 1 year. Only injection site reactions (45% treated v 7% controls) and rash (26% v 2%) occurred more frequently in treated patients (n = 176). These data show that rhGM-CSF is well tolerated in most patients with NHL, significantly reduces infection, and improves response.