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.

- 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. REMoDL-B Protocol
Version 2.0 6th January 2011.

- 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.

- 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. Patients
who are HepBsAg positive 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.

- Any co-existing medical or psychological condition that would compromise ability to
give informed consent.