A phase II study of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy (ER-CHOP) in patients with previously untreated diffuse large B-cell lymphoma

Abstract

8500 Background: A prior pilot study of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy (ER-CHOP) in untreated patients with diffuse large B-cell lymphoma demonstrated feasibility and safety. This multicenter phase II study was carried out to assess efficacy. Methods: Patients received chemotherapy on the following schedule: epratuzumab 360 mg/m2, rituximab 375 mg/m2, and standard dose CHOP every 3 weeks for 6 cycles. Weekly blood counts were obtained to monitor hematological toxicity. Primary endpoint was 12 month event free survival (EFS12). Secondary endpoints were complete response rate (CR), overall response rate (ORR). An interim analysis was planned when the first 34 eligible patients are evaluable for EFS12. Results: 107 patients were accrued from Feb 2006 to Aug 2007. 29 patients were ineligible based on CD22 negative (11), inadequate pathology or transformed histology (17), or cancel (1) resulting in 78 evaluable patients. Baseline patient characteristics for the entire patient population included median age 62 (range 21–82); 59 patients were male. Most patients had advanced stage (82%); majority had low or intermediate IPI. 72 (67%) patients had an elevated LDH. Performance sore was 0–1 in 94 pts and 2–3 in 13 pts. Overall, 104 patients are evaluable for toxicity. 71 patients (68%) developed grade 4 neutropenia, grade 3 or 4 anemia (9%) and thrombocytopenia (13%). Non- hematological adverse events included neuro-sensory (45%), fatigue (36%), and vomiting (28%). The most common grade 3 or 4 treatment related event was febrile neutropenia (17%). This study has met full accrual. At the time of the planned interim analysis, response rate for these 34 patients is 16 CR, 3 CRu (56% CR + CRu), 13 PR (38%), and 2 SD with an ORR of 94%. Data on the primary endpoint (EFS12) is still maturing and will be reported at the meeting. Conclusions: ER-CHOP every 21 days is safe. The ORR is encouraging; further analysis will determine if this regimen should be evaluated in a phase III randomized study. No significant financial relationships to disclose.