Characteristics and Effectiveness of Rituximab (R) Maintenance Regimens Among US Patients Diagnosed with Follicular Lymphoma (FL) 2004–2007,

Rituximab maintenance (RM) following induction therapy has been demonstrated to increase PFS in randomized trials in both first-line and relapsed settings (ECOG 1496, EORTC 20981, and most recently, PRIMA), and RM has been frequently used in clinical practice in the U.S. and other countries. We examined the various RM approaches used by practicing physicians in the U.S., factors that predicted whether RM was used, and compared the “real-world” effectiveness of RM to the outcomes of observation (Obs) following front-line R-based induction in FL patients (pts).

The National LymphoCare Study is a prospective, multi-center, longitudinal, observational study that collects data on treatment and outcomes for pts diagnosed with FL in the U.S. from 2004–2007. Pts who achieved complete response (CR), partial response (PR) or stable disease (SD) following initial treatment with R-based therapy and who did not initiate second line therapy during the 215-day period following the date of last dose of initial therapy were categorized as Obs. Pts meeting the same criteria who started maintenance R treatment in the 215-day period comprise the RM group. Multivariable logistic regression analyses were performed to identify characteristics related to receiving RM. We compared RM and Obs groups in progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) using Cox proportional hazards models controlling for confounding factors of clinical interest (sex, FLIPI risk group, treatment setting [academic vs. community], and induction therapy). PFS was defined as the number of days from the 215 day period following induction that defined the Obs and RM groups up to and including the date of disease progression as assessed by the treating physician or death from any cause. Pts who had not yet experienced a PFS event at the time of analysis were censored at the date of the most recent response assessment.

Of the 2,732 pts enrolled in NLCS, 1,536 pts completed R-based induction therapy. Among these,1,236 pts achieved CR/PR/SD and met other criteria described above to be included in analysis. 557 pts started RM treatment in the 215-day post-induction work up period (128 following R and 429 following R-chemo), and 679 pts were observed (125 following R and 554 following R-chemo). The mean duration of RM was 528 days, and the mean number of RM doses received was 13. 23% received Rx4 every 6 months, 20% Rx1 every 2 or 3 months, and 57% received another schedule. 14% of pts discontinued RM early (n=79). The most common reasons for early discontinuations were disease progression (29%), toxicity (11%), or death (7%). Pts who received R induction were more likely to receive RM than those who received R-chemo as induction (51% vs. 44%). Pts treated in community practices were slightly more likely to receive RM compared with those who were treated in academic centers (46% vs. 40%). In multivariable models, the most significant predictors of receiving RM were grade (I/II), stage (III/IV), geographic region (other than West), community practice setting, and R induction treatment (all p<0.05). After adjusting for FLIPI risk group, induction treatment, and clinical factors, RM significantly improved PFS (HR= 0.72; p= 0.010) and TTNT (HR= 0.74; p= 0.03). At 4 years of follow-up, 11% of pts in the combined population have died and there was no significant difference in OS between RM and Obs groups. 22% (n=124) of RM pts had received 2nd line treatment at the time of analysis, of whom 36% received R alone and 31% received R-chemo. The response rate for 2nd treatment was similar between RM and Obs groups (60% CR/PR for both groups).

RM following front-line R-based induction was common in this period. However, a large percentage of pts received a RM schedule that was not consistent with standard published schedules reflecting variation among community practices. Nevertheless, RM use in clinical practice produced significant differences in PFS and TTNT compared to Obs. Importantly, response to second-line treatment was similar between RM and Obs groups. Additional followup is needed to determine whether RM produces OS benefits in this context.

Sinha:Celgene: Research Funding. Zhou:RTI-HS: Employment; Novartis: Research Funding. Friedberg:Genentech: Consultancy; astellas: ; Lilly: ; Abbott/Trubion: ; Seattle Genetics: Honoraria; Cephalon: Consultancy. Hirata:Genentech Inc/Roche: Employment; Roche: Equity Ownership. Flowers:Spectrum: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech/Roche (unpaid): Consultancy; Novartis: Research Funding; Seattle Genetics: Consultancy.