Rituximab and CHOP Chemotherapy Plus GM-CSF for Previously Untreated Diffuse Large B-Cell Lymphoma in the Elderly: A Wisconsin Oncology Network Study

Department of Medicine, University of Wisconsin School of Medicine and Public Health and UW Carbone Cancer Center, Madison, WI, USA.
Clinical lymphoma, myeloma & leukemia (Impact Factor: 2.02). 10/2010; 10(5):379-84. DOI: 10.3816/CLML.2010.n.071
Source: PubMed


Human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) may potentiate rituximab activity by upregulating CD20 expression and activating effector cells necessary for antibody-dependent cellular cytotoxicity. GM-CSF was combined with standard rituximab + CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy (R-CHOP) in the treatment of elderly patients with de novo diffuse large B-cell lymphoma (DLBCL).
Thirty-eight patients over the age of 60 years with newly diagnosed DLBCL were treated with R-CHOP every 21 days for 6-8 cycles and GM-CSF 250 µg/m2 per day on days 3-10. Patients were evaluated for response after cycles 4, 6, and 8. The primary endpoint was the rate of complete response, and secondary endpoints were progression-free survival (PFS), event-free survival, and overall survival (OS).
Thirty-eight patients were enrolled, with a median age of 72 years, and 29% of patients having high-risk disease (International Prognostic Index [IPI] score ≥ 4). A complete or unconfirmed complete response (CR) was achieved in 53% of patients. After a median follow-up of 51.1 months, the 3-year PFS and OS were 78% and 84%. Twenty-one percent of patients discontinued protocol treatment because of chemotherapy-related toxicity and 16% because of GM-CSF toxicity. Dose intensity for planned chemotherapy cycles was 81.1%.
These data suggest that survival outcomes may be modestly improved when GM-CSF is combined with R-CHOP in the treatment of elderly DLBCL. GM-CSF had toxicity precluding planned administration in 16% of patients, which may limit usefulness of this agent. Further investigation of GM-CSF in combination with rituximab-containing chemotherapy is warranted.

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    ABSTRACT: Granulocyte-macrophage colony stimulating factor (GM-CSF) has been shown to enhance CD20 antigen expression, augment antibody-dependent cell-mediated cytotoxicity, and stimulate immune cell proliferation. This may lead to an improved anti-tumor effect of rituximab while reducing the severity of chemotherapy-induced myelosuppression. We evaluated the safety and efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in sequential combination with GM-CSF priming and rituximab in previously untreated patients (n = 39) with diffuse-large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). CHOP was administered every 21 days on day 1, GM-CSF 250 μg/m(2)/day on days 9 through 15, and rituximab 375 mg/m(2) on day 15 of each cycle. The overall response rate was 87%, with complete response in 64%. At a median follow-up of 84.3 months, the overall and progression-free survival rates were 54% and 49%, respectively. The most common toxicity was myelosuppression. Sequential combination of CHOP with GM-CSF priming and rituximab was feasible and effective, warranting further evaluation.
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