Rituximab Plus CHOP Given Every 15 Days with GM-CSF (sargramostim) In Patients Withnewly Diagnosed Diffuse Large B-Cell Lymphoma

The R-CHOP regimen administered every three weeks has become the standard of care for treatment of patients with diffuse large B-cell lymphomas. Previous studies have not shown an advantage of dose dense (cycles given every 2 weeks) R-CHOP therapy. Granulocyte-macrophage colony stimulating factor (GM-CSF), in addition to stimulating hematopoetic recovery augments dendritic cell numbers and promotes antigen presentation, induces immune recognition of tumor cells, causes antibody dependent cytotoxicity, and upregulates activity of rituximab. In a Phase II study, we analyze the efficacy and tolerability of R-CHOP given every 15 days with GM-CSF administered on days 3 through 13 of each cycle.

All patients were treated with Rituximab, 375 mg/m2; Cyclophosphamide, 750 mg/m2; Doxorubicin, 50 mg/m2; Vincristine, 1.4 mg/m2, all given IV on day 1; oral prednisone 100 mg given orally on days 1–5 and subcutaneous GM-CSF, 250 mg/m2 on days 3–13. Chemotherapy cycles were repeated every 15 days.

In this mid-study evaluation, thus far 36 patients with a median age of 53 (range 22–81) have been accrued. All patients were previously untreated and had CD20+ diffuse large B cell lymphoma. 26 (72%) patients had stage III (8) or IV (18) disease. Thirteen (36%) patients had bone marrow involvement. Twenty eight (77%) had elevated serum LDH levels, and 16 (44%) patients had an intermediate or high risk IPI score. Toxicities have been primarily hematologic with transient grade 3 or 4 neutropenia in 27 (74%) patients; grade 3 anemia in 6 (16%) patients; and grade 3 or 4 thrombocytopenia in 4 (11%) patients. In addition, 4 patients experienced neutropenic fever. Non-hematologic side effects of note were grade 3 mucositis/stomatitis in 2 patients; grade 3(n=1) and grade 4 (n=1) cardiac dysfunction in 2 patients. IgG, IgA, IgM levels were all decreased after 2 cycles of chemotherapy. Further cycles did not affect immunoglobulin levels. Of the 34 patients evaluable for response, 24 (71%) achieved complete remission, 7 (21%) achieved partial remission, 1 (3%) had stable disease, and 2 (6%) had progression of disease.

The mid study evaluation confirms that R-CHOP given every 15 days with GM-CSF (sargramostim) administered on days 3 through 13 of each cycle provides promising response rates with tolerable toxicity.

Tulpule: Genzyme, I am the PI on this study funded by Genzyme.: Research Funding.