Dose-dense R-CHOP (administered every 2 weeks) with sargramostim in patients with newly diagnosed diffuse large B-cell lymphoma.

Abstract

8554 Background: R-CHOP administered every 3 weeks is standard of care for the treatment of diffuse large B-cell lymphoma (DLBCL). There are conflicting reports regarding the superiority of dose dense (DD) regimen (R-CHOP administered every 2 weeks), compared to the standard R-CHOP regimen. In a Phase II study, the tolerability and efficacy of DD-RCHOP+Sargramostim was evaluated. Methods: All patients received intravenous rituximab, 375 mg/m2; cyclophosphamide, 750 mg/m2; doxorubicin, 50 mg/m2 and vincristine, 1.4 mg/m2 on day 1; prednisone 100 mg orally on days 1-5 and sargramostim 250 mg/m2subcutaneously on days 3-13. Chemotherapy cycles were repeated every 2 weeks. Results: We studied50 newly diagnosed, previously untreated DLBCL patients (median age 54.1 years, range 21.4-80.3 years). Stage III and IV disease was noted in 12 (24%) and 29 (58%) patients, respectively. Baseline characteristics included the following: high-intermediate or high-risk IPI score (n=38, 76%), extranodal involvement (n=32, 64%), bone marrow infiltration (n=5, 10%), B-symptoms (n=23, 46%), median LDH level (272, range 118-3797) and good baseline performance status (n=45, 90%). The median follow up from the start of treatment was 12.7 months (range 0.1-41.4 months). Among the 46 patients evaluated for response, complete response (CR) or unconfirmed CR (CRu) was observed in 36 (78%) patients, partial response (PR) or an unconfirmed PR in 9(20%) patients and 1 patient had stable disease. The probability of overall survival (OS) at 18 months was 0.84. The probability of disease free survival in complete responders at 9 months was 0.89. Neutropenia was the most common hematological toxicity and accounted for delays in 40 (20%) treatment cycles. There were no episodes of fever/sepsis in the 33 patients (66%) with grade 3 or 4 neutropenia. IgG, IgA and IgM levels decreased during therapy and returned to normal in 2-4 months post therapy. No opportunistic infections were reported. Conclusions: The administrationof DD-RCHOP+Sargramostim regimen is safe, tolerable and effective in patients with newly diagnosed DLBCL. However, neutropenic episodes were significant, accounting in many cases for treatment delays.