A Randomised Evaluation of Molecular Guided Therapy for Diffuse Large B-cell Lymphoma With Bortezomib

Inclusion Criteria: * Histologically confirmed DLBCL, expressing CD20. Sufficient diagnostic material should be available to forward to Haematological Malignancies Diagnostic Service (HMDS) for gene expression profiling and central pathology review. Core biopsies are acceptable, however the molecular profiling success rate is inferior compared to larger surgically acquired tissue samples. Best diagnostic practice encourages investigators to seek the latter approach whenever clinically appropriate. * Measurable disease of at least 15mm. * Not previously treated for lymphoma and fit enough to receive combination chemoimmunotherapy with curative intent. * Age \> 18 years. * Stage IAX (bulk defined as lymph node diameter \> 10cm) to stage IV disease and deemed to require a full course of chemotherapy. * ECOG performance status 0-2. * Adequate bone marrow function with platelets \> 100x109/L; neutrophils \>1.0x109/L at study entry, unless lower figures are attributable to lymphoma. * Serum creatinine \< 150μmol/L, measured or calculated creatinine clearance \> 30mls/min, serum bilirubin \< 35μmol/L and transaminases \< 2.5x upper limit of normal at the time of study entry, unless attributable to lymphoma. * Cardiac function sufficient to tolerate 300mg/m2 of doxorubicin. A pre-treatment echocardiogram is not mandated, but recommended in patients considered at higher risk of anthracycline cardiotoxicity. * No concurrent uncontrolled medical condition. * Life expectancy \> 3 months. * Adequate contraceptive precautions for all patients of child bearing potential. * A negative serum pregnancy test for females of child bearing potential or those \< 2 years after the onset of the menopause. * Patients will have provided written informed consent. Exclusion Criteria: * Previous history of treated or untreated indolent lymphoma. However newly diagnosed patients with DLBCL who are found to also have small cell infiltration of the bone marrow or other diagnostic material (discordant lymphoma) will be eligible. * Diagnosis of primary mediastinal lymphoma * Uncontrolled systemic infection. * History of cardiac failure of uncontrolled angina. * Clinical CNS involvement. * Serological positivity for Hepatitis C, B or known HIV infection. Viral serological testing is not mandated for study entry, but considered standard of care. (• Positive test results for chronic HBV infection (defined as positive HBsAg serology) will not be eligible. • Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) will not be eligible as one would normally monitor HBV DNA serially and add lamivudine if copy number became detectable. There is an interaction between lamivudine and bortezomib. Reactivation of latent infection has been reported with the use of bortezomib in this population (along obviously with the well recognised reactivation following R-CHOP). For these patient safety reasons, these patients should be excluded. • Patients who have protective titres of hepatitis B surface antibody (HBSAb) after vaccination are eligible. • Positive test results for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing) will not be eligible.) * Serious medical or psychiatric illness likely to affect participation or that may compromise the ability to give informed consent. * Active malignancy other than fully excised squamous or basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix in the preceding 5 years. * History of allergic reaction to substances containing boron or mannitol. * Patient unwilling to abstain from green tea and preparations made from green tea as bortezomib may interact with these.