Randomized phase II study of concurrent and sequential combinations of rituximab (R) plus CHOP (R-CHOP) in untreated indolent B-cell non-Hodgkin's lymphoma (B-NHL)

Abstract

6577 Background: R-CHOP is regarded as the best available treatment for untreated patients (pts) with indolent and aggressive B-NHL; however, the optimal combination schedule in indolent B-NHL remains unknown. Methods: Previously untreated pts with indolent B-NHL of advanced stages were randomly allocated to the concurrent arm (Arm C) or the sequential arm (Arm S). All pts received 6 cycles of standard CHOP every 3 weeks. In addition, Arm C received R at 375 mg/m2, 6 times, 2 days prior to each cycle of CHOP, whereas Arm S received R at 375 mg/m2, weekly 6 times, following 6 cycles of CHOP. Pts were monitored for clinical response by the International Workshop Criteria, molecular response by PCR assay for bcl-2 rearrangement in bone marrow and peripheral blood, and adverse events for at least 3 years or until progression. The primary endpoint was the overall response rate (ORR). Results: Between July 1999 and July 2000, a total of 69 pts were enrolled, and 66 (Arm C, 32; Arm S, 34) of them were eligible. The two arms were comparable in major prognostic features. A central pathology review revealed follicular lymphoma accounted for 95%. ORR represented 94% (30/32; 95% confidence interval [CI], 79–99%) including 81% of complete response (CR) in Arm C and 97% (33/34; 95% CI, 85–100%) including 85% of CR in Arm S. The time to achieving response in 75% of the pts was 66 days (95% CI, 63–76 days) in Arm C and 127 days (95% CI, 66–135 days) in Arm S (P=0.099). Molecular response occurred more promptly in Arm C. Grade 4 hematologic toxicities were observed in 85% in Arm C and 70% in Arm S, and grade 3 or greater non-hematologic toxicities in 19% in Arm C and in 9% in Arm S. Both arms were well tolerated. The median progression-free survival (PFS) time was 864+ days in Arm C and 920+ days in Arm S (P=0.322). Eighteen pts (58%) in Arm C and 23 pts (70%) in Arm S were continuously progression-free. Conclusions: R-CHOP is highly effective for untreated indolent B-NHL either by concurrent or sequential combination. The time to response is more prompt with the concurrent combination, whereas PFS appears to be longer with the sequential combination. No significant financial relationships to disclose.