A Randomized, Multicenter, Phase III Trial Comparing Treatment With R-mini-CHOP With R-mini-CHP + Polatuzumab Vedotin in Patients With Diffuse Large Cell B Cell Lymphoma

Inclusion Criteria:

• Age ≥80 years or frail ≥75 years, according to simplified comprehensive geriatricassessment

• Histologically confirmed lymphoma belonging to one of the following subtypes:

1. diffuse large B-cell lymphoma, including transformation from an indolentlymphoma

2. follicular lymphoma grade 3B

3. T-cell/histiocyte-rich LBCL

4. primary cutaneous DLBCL, leg type

5. EBV-positive DLBCL, NOS

6. primary mediastinal LBCL

7. high grade B-cell lymphoma with MYC/BCL2 rearrangement

• Stage II-IV disease

• At least 1 measurable site of disease (>1.5 cm long axis)

• No previous treatment for lymphoma

• WHO performance status 0 - 3 (Grade 3 if related to DLBCL)

• Written informed consent

Exclusion Criteria:

• Severe cardiac disease: NYHA grade 3-4

• CNS involvement at diagnosis

• Uncontrolled serious infection

• Impaired liver (transaminases > 3x normal upper limit or bilirubin > 1.5 x normalupper limit, unless due to Gilbert´s syndrome) , renal (GFR<30ml/min) or other organfunction not caused by lymphoma, which will interfere with the treatment.

• Absolute neutrophil count (ANC) <1000 cells/µL or platelets <100,000 cells/µL,unless due to lymphoma

• Any other prior malignancy than non-melanoma skin cancer or stage 0 (in situ)cervical carcinoma, unless treated with curative intent, and without relapse since 2years, or low grade prostate cancer, not in need of treatment

• Psychiatric illness or condition which could interfere with their ability tounderstand the requirements of the study

• Known hypersensitivity to rituximab, polatuzumab vedotin, cyclophosphamide,vincristine or doxorubicin, or HACA against rituximab

• Peripheral neuropathy grade ≥ 2