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Combination of novel molecular targeted agent plus R-CHOP-based regimen versus R-CHOP alone in previously untreated diffuse large B-cell lymphoma (DLBCL) patients: a systematic review and meta-analysis.

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Abstract

The addition of molecular targeted agents (MTAs) to R-CHOP has been one of the main focuses of research in patients with DLBCL. Despite encouraging preliminary results, recent randomized controlled trials (RCT) have not shown a definitive benefit over standard R-CHOP. Here we conducted a systematic review and meta-analysis to investigate the impact of this strategy. A systematic literature review was conducted to identify RCT that evaluated the addition of MTA to R-CHOP-based regimen versus R-CHOP alone in previously untreated DLBCL patients. Fixed and random effects models were used to estimate pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI). Progression-free survival (PFS), overall survival, and adverse events (AE) were analyzed. A total of seven RCT including 3,255 patients with DLBCL met the eligibility criteria. Three different types of MTAs (bortezomib, ibrutinib, and lenalidomide) were investigated in combination with R-CHOP. Overall, R-CHOP plus MTA showed a slightly better PFS (HR=0.86; 95% CI: 0.76–0.98). No differences were observed according to the cell of origin subtype of DLBCL. Interestingly, patients younger than 60 years had a significantly better PFS with R-CHOP plus MTAs (HR=0.72; 95% CI: 0.56–0.93), while no benefit was observed in patients older than 60 years (HR=0.96). The combination strategy showed higher odds to develop serious AEs (OR= 1.46, 95% CI 1.11–1.91). R-CHOP plus MTA seems only to slightly improve PFS in patients with DLBCL, particularly in younger patients. An increase in toxicity was observed in comparison to R-CHOP.

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Acknowledgements

The authors thank the REMoDL-B investigators for providing additional data for the analysis.

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Authors and Affiliations

  1. Oncology Data Science (OdysSey) Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

    Guillermo Villacampa & Rodrigo Dienstmann

  2. Department of Hematology, Vall d’Hebron University Hospital, Pssg Vall d’Hebron 119-129, 08035, Barcelona, Spain

    Francesc Bosch & Pau Abrisqueta

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  1. Guillermo Villacampa
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Correspondence to Pau Abrisqueta.

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Conflict of interest

G.V has received honoraria for speaker activities from Merck Sharp & Dohme and advisory role from AstraZeneca.

R.D has received advisory role for Roche and Boehringer Ingelheim and has received a speaker’s fee from Roche, Ipsen, Amgen, Servier, Sanofi, and Merck Sharp & Dohme and research grants from Merck and Pierre Fabre.

F.B has received honoraria and research grants from Roche, Celgene, Takeda, AstraZeneca, Novartis, AbbVie, and Janssen.

P.A. has received honoraria from Janssen, Roche, Celgene, Abbie, and AstraZeneca.

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Villacampa, G., Dienstmann, R., Bosch, F. et al. Combination of novel molecular targeted agent plus R-CHOP-based regimen versus R-CHOP alone in previously untreated diffuse large B-cell lymphoma (DLBCL) patients: a systematic review and meta-analysis.. Ann Hematol 100, 2969–2978 (2021). https://doi.org/10.1007/s00277-021-04623-8

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