Background: Rituximab maintenance (RM) following induction therapy has been demonstrated to increase progression-free survival (PFS) in randomized trials in both first-line and relapsed settings (ECOG 1496, EORTC 20981, and PRIMA), and RM has frequently been used in clinical practice in the US and other countries.
Aims: To examine the various approaches to RM used by practicing physicians, the correlates for use of RM, and the ‘real-world’ effectiveness of RM compared with observation (Obs) in patients with FL.
Methods: The National LymphoCare Study (NLCS) is a multicenter, longitudinal, observational study of newly diagnosed FL patients enrolled from 2004 to 2007. All patients gave consent and were treated according to the enrolling physicians’ preference; patients were followed for disease progression, retreatment, and overall survival (OS). Patients who achieved complete response, partial response, or stable disease following induction treatment with R-based therapy and had not initiated second-line therapy during the 215-day period following the date of last dose of induction therapy were categorized as Obs in this analysis, and those who started maintenance treatment during the 215-day period composed the RM group. Predictors for receiving RM were identified using multivariate logistic regression analysis with backward stepwise selection. RM and Obs groups were compared for PFS, time to next treatment (TTNT), and OS using Cox proportional hazards models.
Results: Of 2727 evaluable NLCS patients, 1204 completed R-based induction therapy and met all inclusion criteria for this analysis. 538 patients started RM treatment in the 215-day post-induction period and 666 patients were observed. The mean time to first RM dose was 4 months and mean duration of RM was 18 months. A total of 82% of RM patients completed their planned maintenance treatment regimen, 13% prematurely discontinued, and treatment was still ongoing for 5%. Predictors (p<0.05) for receiving RM over Obs were histology grade (1/2), stage (III/IV), geographic region (other than West), and center type (community practice). PFS and TTNT in the RM group were longer than those in the Obs group. With a median follow-up of 53 months after induction, OS was comparable between RM and Obs groups (HR=0.79; p=0.27). Adjusting for factors, including the Follicular Lymphoma International Prognostic Index, RM was associated with superior PFS (HR=0.69; p=0.003), longer TTNT (HR=0.73; p=0.03), but there was no difference in OS compared with Obs. The efficacy of RM treatment was not affected by the type of frontline regimen. At the time of analysis, 22% of RM patients had received second-line treatment; of these, 33% received R-monotherapy and 32% R-chemotherapy. In the Obs group, 25% received second-line treatment, 41% R-monotherapy, and 27% R-chemotherapy. The response rate for second-line treatment was similar between groups.
Conclusions: NLCS data on physician-directed strategies following R-based induction provide useful information for comparing the effectiveness of RM and Obs in clinical practice. In this setting, RM treatment following R-based induction therapy produced significantly longer PFS and TTNT compared with Obs. Longer follow-up is required to determine whether this will produce differences in OS.
