Inclusion Criteria:  Age ≥18yo and ≤65yo at the time of signing consent  Have a histologically confirmed diagnosis of one of the following, according to the 2016 WHO classification:  DLBCL, NOS or DLBCL arising as a result of transformation of an indolent lymphoma HGBL, NOS HGBL with rearrangements of MYC and BCL2 and/or BCL6  For DLBCL, and HGBL, NOS meets one of the following risk criteria:  a. NCCN-IPI of ≥4 or IPI ≥3 (appendix 1 and 3)  Considered fit for 6 cycles of full dose R-CHOP chemotherapy, as per the Investigator  ECOG performance status (appendix 5) of:  0-2 inclusive or 3 if directly attributable to lymphoma for patients entering the trial prior to cycle 1 of R-CHOP 0-1 inclusive for patients entering the trial at cycle 2 Patients must be treatment-naïve or have received a maximum of one cycle of full-dose R-CHOP chemotherapy (with or without a steroid pre-phase) Able to provide an archival pre-treatment biopsy. Have measurable disease on a pre-chemotherapy PET/CT, defined as at least one bi-dimensionally measurable nodal lesion of >1.5cm in longest dimension, or at least one bi-dimensionally measurable extranodal lesion of >1.0cm in longest dimension Life expectancy (in the opinion of the Investigator) of ≥ 18 weeks Adequate haematological function Adequate renal function Adequate hepatic function Negative serologic or PCR test results for active acute or chronic HBV infection. Non-haematological AEs from prior anti-cancer therapy must have resolved to Grade ≤1 (with the exception of alopecia and inclusion criteria 10-12) Negative test results for HCV and HIV.  Exclusion Criteria:  Inability to comply with protocol mandated hospitalisations and restrictions Prior systemic treatment of an underlying indolent lymphoma with an anthracycline-containing regimen Richter's syndrome Patients with known CNS involvement by lymphoma With the exception of rituximab, any prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immuno-conjugates, antibody-drug conjugates, immune/cytokines, and monoclonal antibodies within 4 weeks or five half-lives of the drug, whichever is shorter, before the first dose of study drug With the exception of CHOP used as a first cycle of lymphoma treatment, any chemotherapeutic agent, or treatment with any other investigational agent within 4 weeks prior to study treatment Prior solid organ transplantation Prior autologous or allogeneic stem cell transplantation A history of treatment-emergent immune related AEs associated with prior immunotherapeutic agents  Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease  Note: patients with a history of stroke who have not experienced a stroke or transient ischaemic attack in the past 2 years are allowed Note: patients with a history of epilepsy who have not experienced a seizure in the past 2 years are allowed, so long as continuation of any ongoing established pharmacologic treatment is not contraindicated Past history of confirmed progressive multifocal leukoencephalopathy Past history of chronic active EBV or HLH Major surgery or significant traumatic injury <28 days prior to study treatment or anticipation of the need for major surgery during study treatment  Significant cardiovascular disease, defined as:  A left ventricular ejection fraction (as determined by nuclear gated blood pool scan or echocardiogram) <50% Myocardial infarction or unstable angina within the past 6 months Unstable arrhythmia Any other cardiac illness that, in the opinion of the Investigator or CPI, makes the patient unsuitable for anthracycline containing therapy Significant pulmonary disease, including but not limited to clinically significant obstructive pulmonary disease or history of bronchospasm Current grade >1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease Known clinically significant liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosis Administration of a live, attenuated vaccine within 4 weeks before study treatment note: influenza vaccination should be given during influenza season only. Patients must not receive live, attenuated influenza vaccine at any time during the study treatment period  History of other active malignancy within 5 years prior to registration, with the exception of:  FL or MZL, previously untreated, or treated with no more than one line of therapy which must not have contained an anthracycline Basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix Prior malignancy treated with a curative intent that has remained in remission without treatment for ≥2 years prior to registration  Patients with known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of the nail beds) at registration  a. Note: Patients with latent tuberculosis are excluded  Other significant life-threatening illness or medical condition which, in the Investigator's opinion, could compromise the patient's safety, interfere with absorption or metabolism of study drug, affect compliance with the protocol or interpretation of results, or put the study outcomes at undue risk Major contraindication to any of the individual components of the chemotherapy backbone (R, C, H, O, Polatuzumab vedotin, prednisolone) Patients who are pregnant or breastfeeding  Other protocol-defined inclusion and exclusion criteria may apply.