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R-GEM-Lenalidomide versus R-GEM-P as second-line treatment of diffuse large B-cell lymphoma: results of the UK NRCI phase II randomised LEGEND trial

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Abstract

Outcome of patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) remains poor, highlighting the need for novel treatment approaches. The multicentre randomised phase II LEGEND trial evaluated lenalidomide in combination with rituximab, methylprednisolone and gemcitabine (R-GEM-L) vs. standard R-GEM-P as second-line treatment of DLBCL. The study closed early to recruitment after the planned interim analysis failed to demonstrate a complete response (CR) rate of ≥ 40% in either arm. Among 34 evaluable patients, 7/18 (38.9%) achieved CR with R-GEM-L and 3/16 (18.8%) with R-GEM-P. Median event-free and overall survival was 3.5/3.8 months and 10.8/8.3 months for R-GEM-L and R-GEM-P, respectively. The incidence of grade ≥ 3 toxicities was 52% in R-GEM-L and 83% in R-GEM-P. Efficacy and tolerability of R-GEM-L seem comparable with R-GEM-P and other standard salvage therapies, but a stringent design led to early trial closure. Combination of lenalidomide with gemcitabine-based regimens should be further evaluated in r/r DLBCL.

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  • 30 December 2020

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Acknowledgements

We would like to thank participating centres of the LEGEND trial, as well as patients and their families involved. The study was in part supported by a research grant from Celgene Corporation. NanoString analyses were funded by a grant from the Royal Marsden National Institute for Health Research (NIHR) Biomedical Research Centre. Site accreditation, data collation and quality control for PET imaging was performed by the UK PET Core lab. K.M.A is supported by the UCL/UCLH Biomedical Research Centre.

Funding

I.C. has received research funding from Eli-Lilly, Janssen-Cilag, Sanofi Oncology, Merck Serono, and Novartis; participated on advisory boards for Sanofi Oncology, Eli-Lilly, Bristol-Myers Squibb, Merck Sharpe Dohme (MSD), Bayer, Roche and Five Prime Therapeutics; and received honoraria from Taiho, Pfizer, Amgen and Eli-Lilly. D.C. has received research funding from Amgen, AstraZeneca, Bayer, Celgene, Medimmune, Merck Serono, Merrimack and Sanofi.

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Authors and Affiliations

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Contributions

A.K.: trial physician, contributed to the conduct of the study, analysed and interpreted data, and wrote the report. C.P.: trial statistician, designed the study, analysed data and contributed to writing of the report. B.P.: trial coordinator, gathered, entered and coordinated data. K.M.A, M.P.M, J.R., R.J., S.P: co-investigators, gathered and interpreted data. S.B.: contributed to the study design. I.C.: contributed to the study conduct. R.B.: trial specimen coordinator, gathered tissue for central review. N.V.: performed NanoString analyses. A.W.: trial histopathologist, performed central histopathology review. Y.D., I.Z.: trial radiologists, performed central radiology review. D.C.: chief investigator, responsible for the study conduct and final report. All authors reviewed and approved the final version of the report.

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Correspondence to David Cunningham.

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Kühnl, A., Peckitt, C., Patel, B. et al. R-GEM-Lenalidomide versus R-GEM-P as second-line treatment of diffuse large B-cell lymphoma: results of the UK NRCI phase II randomised LEGEND trial. Ann Hematol 99, 105–112 (2020). https://doi.org/10.1007/s00277-019-03842-4

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Keywords

  • DLBCL
  • Second-line therapy
  • Lenalidomide