Kahl BS, et al. ASH 2017:484

Assessment of maintenance rituximab after first-line BR in patients with FL: An analysis from the BRIGHT trial

Background

Maintenance rituximab (R-maintenance) has demonstrated improved progression-free survival (PFS) in patients with follicular lymphoma (FL) who responded to first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone).1 It is unknown whether R-maintenance following bendamustine plus rituximab (BR) confers similar benefits. Given the widespread uses of BR and R-maintenance in the treatment of FL, it is important to determine the impact of R-maintenance following BR on efficacy and toxicity. The design of the BRIGHT trial allowed for an ad hoc analysis of this issue with regards to efficacy. Results of this analysis were presented at the 2017 ASH Annual Meeting.2

Study design

  • The BRIGHT study compared BR to R-CHOP/R-CVP in treatment-naïve patients with indolent non-Hodgkin lymphoma or mantle cell lymphoma.3
  • The cohort for the ad hoc analysis included 288 patients with FL who achieved a complete or partial response in the BRIGHT study.
  • R-maintenance was administered at the investigator’s discretion.
  • Treatment arms were subdivided by whether or not patients received R-maintenance and were analyzed for baseline characteristics, duration of response (DOR), and overall survival (OS).
  • DOR and OS were assessed from the end of induction study treatment (i.e., BR or R-CHOP/R-CVP).
  • P-values were determined by the log-rank test unless otherwise indicated.

Study design

Key findings

Baseline characteristics and disposition

  • For baseline characteristic data, p-values were calculated using the Kruskal-Wallis test for age and Pearson’s chi-square test for all other variables.
  • In the R-CHOP/R-CVP arm, more patients who received R-maintenance had a FL International Prognostic Index (FLIPI) score of 0–1 at baseline than patients who did not receive R-maintenance (24% vs. 13%; p = 0.0131).
    • Conversely, fewer patients who received R-maintenance had a FLIPI score of 2 at baseline (27% vs. 44%; p = 0.0263).
  • In the BR arm, fewer patients who received R-maintenance had β2-microglobulin >3 mg/L compared to those who did not receive R-maintenance (19% vs. 44%; p = 0.0007).
  • Fewer patients in the BR arm who had R-maintenance achieved a complete response (22% vs. 40%; p = 0.0231).

Efficacy

  • In the R-CHOP/R-CVP arm, DOR was not significantly different between those who received R-maintenance and those who did not (HR = 0.68, 95% CI: 0.39–1.18; p = 0.1676). (Figure 1)
    • OS was also not significantly different between the maintenance groups (HR = 0.32, 95% CI: 0.10–1.05; p = 0.05). (Figure 2)
  • In the BR arm, DOR was prolonged in the R-maintenance group (HR = 0.50, 95% CI: 0.26–0.95; p = 0.0298). (Figure 1)
    • OS was not significantly different between the maintenance groups (HR = 0.39, 95% CI: 0.15–1.06; p = 0.0565). (Figure 3)

Figure 1. Duration of response (all treatments)

Figure 2. Overall survival in FL*: R-CHOP/R-CVP

Figure 3. Overall survival in FL*: BR

Key conclusions

  • DOR was significantly longer in patients treated with BR who received R-maintenance.
    • This overall improvement in DOR appears to be at least as great following BR as following R-CHOP/R-CVP.
  • There was no signal that OS was negatively affected by R-maintenance in responding patients.
  • Since R-maintenance was administered at investigator’s discretion, selection bias may contribute to the observed results.
  • With no randomized controlled trials, assimilation of the total body of work may be needed to make conclusions on the efficacy and risks of using R-maintenance after BR.

References: 1. Salles GA, Seymour JF, Feugier P, et al. Updated 6 year follow-up of the PRIMA study confirms the benefit of 2-year rituximab maintenance in follicular lymphoma patients responding to frontline immunochemotherapy. Blood 2013;122(21):509. 2. Kahl BS, Burke JM, van der Jagt R, et al. Assessment of maintenance rituximab after first-line bendamustine-rituximab in patients with follicular lymphoma: an analysis from the BRIGHT trial. ASH Annual Meeting Abstracts 2017:484. 3. Flinn IW, van der Jagt R, Kahl BS, et al. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood 2014;123(19):2944–52.