Randomized phase II study of concurrent and sequential rituximab and CHOP chemotherapy in untreated indolent B-cell lymphoma

Abstract

CHOP combined with rituximab (R-CHOP) is regarded as one of the most effective treatments for indolent B-cell non-Hodgkin lymphoma (B-NHL), however, its optimal combination schedule remains unknown. We performed a randomized phase II study to explore a more promising schedule in untreated, advanced indolent B-NHL. Patients were randomized to receive either six courses of CHOP concurrently with rituximab (Arm C), or six courses of CHOP followed by six courses of weekly rituximab (Arm S). A total of 69 patients received the concurrent (n=34) or sequential (n=35) regimen. Overall response rate (ORR) in Arm C was 94% (95% confidence interval [CI], 79 to 99), including a 66% complete response (CR) compared with 97% (95% CI, 85-100), including a 68% CR in Arm S. Patients in Arm C experienced more grade 4 neutropenia (85%versus 70%) and experienced more grade 3 or greater non-hematological toxicities (21%versus 12%). Both arms were tolerated well. With a median follow-up of 28.2 months, the median progression-free survival (PFS) time was 34.2 months in Arm C, and was not reached in Arm S. R-CHOP is highly effective in untreated indolent B-NHL, either concurrent or in a sequential combination. Both combination schedules deserve further investigation.

Figure 1

(A) Time to response (TTR) and (B) time to complete response (TTCR). Medians were estimated by the Kaplan‐Meier method. A total of 63 patients (Arm C [‐], 30; Arm S [‐‐‐], 33) were analyzed for TTR, and 44 patients (Arm C, 21; Arm S, 23) for TTCR with per protocol sets of data. Median TTRs in Arm C and Arm S were 61 days (95% confidence interval [CI] 59 to 65 days) and 62 days (95% CI 60–70 days), respectively. The 75th percentile TTRs in Arm C and Arm S were 66 days (95% CI 63 to 76 days) and 140 days (95% CI 66–135 days), respectively (P = 0.0994, log–rank test). Median TTCRs in Arm C and Arm S were 136 days (95% CI 65 to 213 days) and 140 days (95% CI 134–227 days), respectively. The 75th percentile TTCRs in Arm C and Arm S were 228 days (95% CI 141 to 293 days) and 295 days (95% CI 153–323 days), respectively (P = 0.2201, log–rank test).

Figure 2

Progression‐free survival (PFS). Medians were estimated by the Kaplan‐Meier method. The upper limit of the 95% confidence interval (CI) for Arm C has not yet been determined. A total of 65 patients (Arm C, 32; Arm S, 33) were analyzed with per protocol sets of data. The median PFS time for patients in Arm C (‐) was 34.2 months (95%CI, 27.1 months, inestimable), whereas that for patients in Arm S (…) had not yet been reached, with a median follow‐up time of 28.2 months. Log–rank test, P = 0.220. (o) Censored.