Volume 20, Issue 5, Pages 649-662 (May 2019) Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial  Prof Andrew Davies, PhD, Thomas E Cummin, MRCP, Sharon Barrans, PhD, Tom Maishman, PhD, Prof Christoph Mamot, MD, Urban Novak, MD, Josh Caddy, BSc, Louise Stanton, MSc, Shamim Kazmi-Stokes, PhD, Andrew McMillan, FRCPath, Paul Fields, MD, Christopher Pocock, PhD, Graham P Collins, FRCPath, Richard Stephens, MA, Francesco Cucco, PhD, Alexandra Clipson, PhD, Chulin Sha, PhD, Prof Reuben Tooze, PhD, Matthew A Care, PhD, Prof Gareth Griffiths, PhD, Prof Ming-Qing Du, PhD, Prof David R Westhead, DPhil, Catherine Burton, FRCPath, Prof Peter W M Johnson, FMedSci  The Lancet Oncology  Volume 20, Issue 5, Pages 649-662 (May 2019) DOI: 10.1016/S1470-2045(18)30935-5 Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 1 Study profile ITT=intention-to-treat. R-CHOP=rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. RB-CHOP=rituximab, bortezomib, cyclophosphamide, doxorubicin, vincristine, and prednisolone. The Lancet Oncology 2019 20, 649-662DOI: (10.1016/S1470-2045(18)30935-5) Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 2 Progression-free survival in the m ITT population (A), activated B-cell subgroup (B), germinal centre B-cell subgroup (C), and unclassified group (D), by treatment Data are for the mITT population, which comprises germinal centre and activated B-cell ITT participants (n=719); activated B-cell subgroup (n=244); germinal centre B-cell subgroup (n=475); and unclassified subgroup (n=199); with estimated proportions of participants achieving progression-free survival at 12 months and 30 months. HR=hazard ratio. ITT=intention-to-treat. mITT=modified ITT. R-CHOP=rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. RB-CHOP=rituximab, bortezomib, cyclophosphamide, doxorubicin, vincristine, and prednisolone. The Lancet Oncology 2019 20, 649-662DOI: (10.1016/S1470-2045(18)30935-5) Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 3 Progression-free survival comparing double-hit lymphomas to non-rearranged cases (A) and double-expressor (high MYC and high BCL-2 mRNA) lymphomas to all other cases (B), by treatment group Data are progression-free survival and hazard ratio (HR), with non-DHL and non-DEL patients as reference categories. DEL=dual-expressor lymphoma. DHL=double-hit lymphoma. R-CHOP=rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. RB-CHOP=rituximab, bortezomib, cyclophosphamide, doxorubicin, vincristine, and prednisolone. The Lancet Oncology 2019 20, 649-662DOI: (10.1016/S1470-2045(18)30935-5) Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 4 Forest plot of hazard ratios based on progression free survival for participants at high risk and with different molecular subtypes of disease, by treatment group Data are for all randomised participants (ie, ITT population). Hazard ratios and p values are effect estimates from a multivariable model adjusted for IPI score. DEL=dual-expressor lymphoma. DHL=double-hit lymphoma. IPI=international prognostic index. ITT=intention-to-treat. R-CHOP=rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. RB-CHOP=rituximab, bortezomib, cyclophosphamide, doxorubicin, vincristine, and prednisolone. The Lancet Oncology 2019 20, 649-662DOI: (10.1016/S1470-2045(18)30935-5) Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions