Learn more about diffuse large B-cell lymphoma (DLBCL), the most common aggressive form of B-cell non-hodgkin s lymphoma 1

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1 Learn more about diffuse large B-cell lymphoma (DLBCL), the most common aggressive form of B-cell non-hodgkin s lymphoma 1

2 Expression of B-cell surface antigens drives several non-hodgkin s lymphomas (NHLs) 2 Common B-cell surface antigens in DLBCL include 2,3 CD79a ( BCR) CD79b ( BCR) CD20 CD10 CD19 BCR=B-cell receptor. Multiple diagnostic markers are used to diagnose and characterize DLBCL 4 Immunohistochemistry panel for DLBCL* CD20 CD3 CD5 CD10 CD45 Bcl-2 Bcl-6 Ki-67 IRF-4/MUM-1 MYC Flow cytometry panel for DLBCL Kappa/lambda CD45 CD3 CD5 CD19 CD10 CD20 Additional IHC analysis to establish DLBCL subtype Cyclin/D1 Kappa/lambda CD30 CD138 EBER-ISH ALK HHV-8 SOX11 *Typical immunophenotype: CD20+, CD45+, CD3-; other markers used for subclassification. Adequate immunophenotyping to establish diagnosis requires IHC with or without flow cytometry. EBER-ISH=Epstein-Barr encoding region in situ hybridization; HHV-8=human herpes virus 8; IHC=immunohistochemistry. 2

3 DLBCL, the most common and aggressive NHL, comprises 30 58% of all NHLs 3 Though significant strides have been made in the treatment of DLBCL, there is room for improvement 3,5 Incidence rate in the EU: persons 3 5-year overall survival rate (EU) 5 3

4 Prognostic models aid in predicting outcomes based on a patient s clinical characteristics before treatment 3 The International Prognostic Index (IPI) aids in predicting prognosis of patients with aggressive NHL 3 IPI risk factors 3 Age >60 years Ann Arbor stage III/IV More than 1 extranodal site Serum LDH level above normal ECOG performance status 2-4 The IPI predicts risk of disease recurrence and overall treatment outcome through 5 adverse prognostic factors: disease stage, age, performance status, serum LDH levels, and the presence or absence of multiple extranodal sites of lymphoma 6 These risk factors help identify low-risk (0-1 factors), low-/intermediate-risk (2 factors), intermediate-/high-risk (3 factors), and highrisk (4-5 factors) patients 6 ECOG=Eastern Cooperative Oncology Group; LDH=lactate dehydrogenase. The International Prognostic Index 3 Risk group IPI score 3-year OS Low % Low-intermediate 2 81% High-intermediate 3 65% High % OS=overall survival. A comprehensive understanding of risk factors and a patient's IPI score may facilitate better treatment decisions 3 4

5 Current data from clinical studies do not support a clear standard of care for DLBCL patients who are not candidates for SCT upon first relapse 4,7 of patients achieve cure with first-line standard of care for DLBCL 7 of patients relapse or become refractory to first-line treatment, and their outcomes are less certain 7 SCT=stem-cell transplant. Randomized head-to-head studies are needed to identify more efficacious treatments for this underserved patient population 4 5

6 Currently, no therapies are EMA- or FDA-approved for the treatment of DLBCL patients at first relapse A retrospective cohort analysis reviewed outcomes of 4 studies assessing different chemotherapy regimens for patients refractory to first-line therapy 5 Objective response rates % months Patients who do not receive treatment for relapsed or refractory DLBCL face a life expectancy of 3 to 4 months 8 EMA=European Medical Association; FDA=Food and Drug Administration. Clinical trial enrollment is recommended by ESMO treatment guidelines for patients with relapsed or refractory DLBCL 3 ESMO=European Society for Medical Oncology. 6

7 Researchers continue to explore additional options for the treatment of DLBCL 9,10 Antibody drug conjugates Monoclonal antibodies Bispecific antibodies Chimeric antigen receptor T-cell therapy 7

8 Published by F. Hoffmann-La Roche Ltd Global Product Strategy 4070 Basel, Switzerland 2018 All trademarks mentioned herein are protected by law. 6/2018 NP/POV/1805/0002 References: 1. Jaffe ES, Harris NL, Stein H, et al. Introduction and overview of the classification of the lymphoid neoplasms. In: Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: International Agency for Research on Cancer; 2008: Olejniczak SH, Stewart CC, Donohue K, Czuczman MS. A quantitative exploration of surface antigen expression in common B-cell malignancies using flow cytometry. Immunol Invest. 2006;35: Tilly H, Gomes da Silva M, Vitolo U, et al, on behalf of the ESMO Guidelines Committee. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann J Onc. 2015;26:v116-v Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) for B-cell Lymphomas V3, National Comprehensive Cancer Network, Inc All rights reserved. Accessed May 1, To view the most recent and complete version of the guidelines, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK, NCCN, NCCN GUIDELINES, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. 5. Crump M, Neelapu S, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130: International Non-Hodgkin s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-hodgkin s lymphoma. N Engl J Med. 1993;329: Coiffier B, Sarkozy C. American Society of Hematology. Diffuse large B-cell lymphoma: R-CHOP failure what to do? 2016;1: Raut LS, Chakrabarti PP. Management of relapsed-refractory diffuse large B cell lymphoma. South Asian J Cancer. 2014;3: Roche first-quarter results 2018 presentation. jcr:6f4ad9a6-3ece-4184-aff4-ea6cd4a4b7ac/en/irp pdf. Accessed May 1, US National Institutes of Health. ClinicalTrials.gov. NCT Accessed May 1, 2018.