Title: Polatuzumab vedotin in combination for untreated diffuse large B-cell lymphoma [ID3901]
Funder: Department of Health and Social Care

Abstract: Lymphomas are cancers of the lymphatic system, which is a part of the immune system. Lymphomas are divided into Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphomas (NHL) are a diverse group of conditions which are categorised according to the cell type affected (B-cell or T-cell), as well as the clinical features and rate of progression of the disease. The most common B-cell lymphomas are follicular lymphoma which is a slow growing, low grade form of NHL and diffuse large B-cell lymphomas (DLBCL), a fast growing, high grade form of NHL. Some follicular lymphomas transform into high grade DLBCL (transformed high grade follicular lymphoma). The symptoms differ depending on which organ or tissues are affected by the lymphoma. NHL often presents as painless lumps (enlarged lymph nodes) in the neck, armpit or groin but sometimes may start in other parts of the body such as the stomach or bowel (extra-nodal disease). People may also have loss of appetite, tiredness or night sweats._x000D_ _x000D_ There are two biologically distinct subtypes of DLBCL, germinal centre B-cell (which arises in secondary lymphoid organs such as lymph node and spleen) and post-germinal centre (also known as activated B-cell lymphoma) which differ in prognosis. They are distinguished by immunohistochemical testing of gene expression profiling._x000D_ _x000D_ There were 11,944 people diagnosed with NHL in England in 2018[1] . It is estimated that about 53% of people with NHL have DLBCL, which equates to around 6,330 people diagnosed with DLBCL per year[1] . Most people diagnosed with DLBCL are 65 or over[2] ._x000D_ _x000D_ Overall survival rates at 5 years for DLBCL were 59.8% between 2004-2016 [3]. However, diagnosis at early stage and germinal centre DLBCL have a better prognosis [4]. Survival rates at 5 years for large B cell lymphomas were 84.3% and 82.7% for stages I and II and 72.3% and 46.6% for stages III and IV respectively. [3] Current first-line treatment is combination chemotherapy with rituximab. The most widely used first-line chemoimmunotherapy is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone)._x000D_ _x000D_ Sometimes etoposide is added to this regimen or doxorubicin is substituted with a different treatment (such as gemcitabine, etoposide or liposomal doxorubicin). In addition, R-ACVBP (rituximab, doxorubicin, vindesine, cyclophosphamide, bleomycin and prednisolone) can be used instead of RCHOP [5]. NICE guideline NG52 recommends central nervous system-directed prophylaxis for some people._x000D_ _x000D_ References_x000D_ _x000D_ 1. Public Health England - Cancer registration statistics: England 2018 final release – Accessed December 2021_x000D_ 2. Lymphoma association. Diffuse Large B-cell lymphoma. Accessed September 2021._x000D_ 3. Haematological Malignancy Research Network (HMRN) data (2004-2016) Accessed November 2021._x000D_ 4. Cho M, Chung Y, Jang S et al. Prognostic impact of germinal center Bcell-like and non-germinal center B-cell-like subtypes of bone marrow involvement in patients with diffuse large B-cell lymphoma treated with_x000D_ R-CHOP, Medicine: November 2018 - Volume 97 - Issue 45_x000D_ 5. Tilly H, Silva M, Vitolo U et al. (2015) Diffuse large B-cell lymphoma (DLBCL): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology ;26(Suppl 5):v116-v125.

Lay abstract: To appraise the clinical and cost effectiveness of polatuzumab vedotin with RCHP (rituximab, cyclophosphamide, doxorubicin, and prednisolone) within its marketing authorisation for untreated diffuse large B-cell lymphoma.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS