Rituximab Plus CHOP Followed by Maintenance Rituximab as Initial Therapy for Aggressive Non-Hodgkin’s Lymphoma (NHL); Initial Results of Induction Therapy, Including Rituximab Pharmacokinetics, in a Phase II Study.

Background: This study was designed to investigate the activity, safety, and pharmacokinetics of rituximab (Rituxan®, R) plus CHOP induction therapy followed by maintenance R in previously untreated patients with aggressive NHL. The initial results of R-CHOP induction therapy are reported here.

Methods: 105 patients with aggressive NHL (diffuse large B-cell or follicle center/follicular grade III by REAL; Type D, F, G or H by IWF) were enrolled into this open-label, multi-center, community based, single-arm, Phase II trial. Patients received 6 or 8 cycles (per standard practice at each site) of R-CHOP induction therapy (cyclophosphamide 750 mg/m², vincristine 1.4 mg/m², doxorubicin 50 mg/m² IV on Day 1, prednisone 100 mg/day Days 1–5). R 375 mg/m² was given on Day 1 of each cycle, except for cycle 1, when it was given 2–3 days before CHOP administration. Subjects with documented responses (CR/CRu or PR) to induction receive maintenance R (4 weekly infusions) beginning 28 days after the completion of induction and repeated every 6 months for 2 years. The primary endpoints were CR/CRu after the completion of induction and the incidence of R infusion-related toxicity in induction and maintenance. Overall response rate (ORR), infusion times, serious adverse events (SAE), and the partial rituximab pharmacokinetic profile were also measured.

Results: Baseline characteristics of patients enrolled were: median age 59 y (49.5% ≥60 y), IPI ≥3 in 31.4 % patients, Ann Arbor Stage II,III, IV in 21.9%, 39.0%, and 39.0% of patients, respectively. CR/CRu at the end of induction in 105 patients was 51.4% (80.0% ORR). 1.9% of patients had progressive disease (PD) during induction. SAE occurred in 33% of subjects during induction with the most common event being febrile neutropenia (14.3%). 5 subjects died during induction (pulmonary embolus, ruptured abdominal aortic aneurysm, pneumonia x2, unknown cause). Grade 3–4 rituximab infusion-related toxicity occurred in 3.9% of subjects during Cycle 1 which decreased to 0% by Cycle 5. 64.3% of patients received their R infusion within 3 hours on Cycle 2; this increased to 74.7% patients at cycle 6. The partial pharmacokinetic profile (peak and trough concentration) of R was measured in 10 patients and will be presented at the meeting.

Conclusion: Rituximab + CHOP chemotherapy is well tolerated and has an excellent response rate when given in the community setting. The outcomes of maintenance therapy in this study await further follow-up.