Abstract
Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a random-effects Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Progression-free survival (PFS) was compared between 11 modern regimens with different immunochemotherapy and maintenance strategies. G-Benda-G resulted in with the best PFS, with an HR of 0.41 compared to R-Benda, a surface under the cumulative ranking curve (SUCRA) of 0.97, a probability of being the best treatment (PbBT) of 72%, and a posterior ranking distribution (PoRa) of 1 (95% BCI 1–3). This was followed by R-Benda-R4 (HR = 0.49, PbBT = 25%, PoRa = 2) and R-Benda-R (HR = 0.60, PbBT = 3%, PoRa = 3). R-CHOP-R (HR = 0.96) and R-Len-R (HR = 0.97) had similar efficacy to R-Benda. Bendamustine was a better chemotherapy backbone than CHOP either with maintenance (R-Benda-R vs R-CHOP-R, HR = 0.62; G-Benda-G vs G-CHOP-G, HR = 0.55) or without maintenance therapy (R-Benda vs R-CHOP, HR = 0.68). Rituximab maintenance improved PFS following R-CHOP (R-CHOP-R vs R-CHOP, HR = 0.65) or R-Benda (R-Benda-R vs R-Benda, HR = 0.60; R-Benda-R4 vs R-Benda, HR = 0.49). In the absence of multi-arm RCTs that include all common regimens, this NMA provides an important and useful guide to inform treatment decisions.
Highlights
Follicular lymphoma (FL) is the second most common nonHodgkin lymphoma in the United States and Europe [1, 2]
The FOLL05 trial established that R-CHOP was superior to R-CVP in terms of progression-free survival (PFS) [7, 8], and the PRIMA trial demonstrated that rituximab maintenance improved PFS following R-CHOP or R-CVP [9, 10]
Four studies were excluded from the network meta-analysis due to lower relevance: JCOG 0203 (RCHOP-21 vs R-CHOP-14 for indolent NHL), SWOG S0016
Summary
Follicular lymphoma (FL) is the second most common nonHodgkin lymphoma in the United States and Europe [1, 2]. In a subset of patients, treatment can be deferred until symptoms arise or certain criteria are met [3]. Radiation therapy and/or anti-CD20 monoclonal antibody (e.g., rituximab) are among appropriate options for early-stage or low bulk disease [4]. Anti-CD20 antibody-based immunochemotherapy is often indicated for advanced-stage disease [5, 6]. The FOLL05 trial established that R-CHOP was superior to R-CVP in terms of progression-free survival (PFS) [7, 8], and the PRIMA trial demonstrated that rituximab maintenance improved PFS following R-CHOP or R-CVP [9, 10]. Rituximab in combination with bendamustine (R-Benda) emerged as a preferred regimen after the StiL NHL1 trial and the BRIGHT trial. Stil NHL1 trial reported improved PFS with R-Benda vs R-CHOP (without maintenance) [11], and BRIGHT trial showed improved PFS with R-Benda vs R-
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