CAR-T Cell Therapy, Mosunetuzumab and Polatuzumab for Treatment of Refractory/Relapsed Aggressive Non-Hodgkin's Lymphoma (NHL).

Inclusion Criteria: 1. Histologic diagnosis of: 1. Diffuse large B cell lymphoma (DLBCL) not otherwise specified. Patients with primary cutaneous DLBCL of leg-type are eligible if the lymphoma expresses cluster of differentiation 19 (CD19) and if the insurance approves the CAR-T therapy. Similarly. Large cell transformation of nodal or extra-nodal marginal zone lymphoma is eligible only if the insurance allows and the disease shows strong CD19 positivity. On the other hand, post-transplant lymphoproliferative disorders (PTLD) are not allowed due to the frequently required continuation of immunosuppression to avoid organ rejection. 2. Primary mediastinal B cell lymphoma (PMBCL) 3. Transformed follicular lymphoma (TFL). An untransformed follicular lymphoma grade 3B will be considered on a case by case basis, since the genetic signature of grade 3B follicular lymphoma frequently resemble that of DLBCL and the large lymphomatous cells just happen to be organized in a follicular pattern. Recently, Breyanzi has an FDA indication for follicular lymphoma grade 3B. 4. High grade B cell lymphoma (HGBL), other than B-lymphoblastic lymphoma 5. Mantle Cell lymphoma (MCL) 6. Burkitt lymphoma (BL): Although very few reports inform us about the outcome of relapsed/refractory BL, encouraging activity including CRs have been reported with CAR-T and these patients are in need because they do not have enough options available. We will need insurance approval for such enrollment. 2. Additionally, the lymphoma has to be in one of the following status: 1. Primary refractory which for the purpose of this study is defined as failure to obtain any response (PR or CR) after at least 3 cycles of anthracycline-based therapy or persistent disease after 6 cycles of anthracycline-based therapy as documented by a PET/CT scan that is done no later than 2 months after the last (usually the 6th) cycle of primary chemotherapy. In questionable cases, a biopsy should confirm persistence of disease as part of standard of care. In case of mantle cell lymphoma, the primary therapy if does not include an anthracycline, should include either high doses of cytarabine +/-bendamustine and an anti-CD20 antibody (usually rituximab). 2. Relapsed disease that fails to respond (CR or PR) after at least 2 cycles of a platinum and/or cytarabine-based chemotherapy. For the purpose of this study, appropriate regimens include: rituximab, ifosfamide, carboplatin and etoposide (R-ICE), rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP), rituximab dexamethasone cytarabine oxaliplatin (R-DHAOx), rituximab, gemcitabine, cisplatin, and dexamethasone (R-GDP). Rituximab, gemcitabine, and oxaliplatin (R-Gem-Ox) is considered appropriate if the patient fails to obtain at least a PR after 4 doses of oxaliplatin. Patients with MCL who relapse after an anthracycline, bendamustine or cytarabine-based regimen, should have failed two salvage attempts: a molecularly targeting-based regimen including at least a Bruton's tyrosine kinase (BTK) inhibitor with or without venetoclax and a cytotoxic traditional second salvage regimen, unless the two salvage approaches are combined. For example if they fail a salvage with R-ICE + a BTK-inhibitor in combination, they are eligible without the need to be exposed to more therapy. Patients with PMBCL, they should also have failed a traditional salvage regimen and a programmed cell death protein 1 (PD-1) inhibitor-based salvage. 3. Relapse after an autologous stem cell transplantation. At least 3 months should have lapsed between autologous stem cell infusion and initiation of pre-CAR-T lymphodepleting chemotherapy due to the risk of prolonged cytopenias. 3. At least one of the lymphoma lesions should be measurable. For the purpose of this study an involved nodal lesion should be at least 1.5 cm in the longest diameter, while extra-nodal lymphoma lesions should have their longest diameter ≥1.0 cm 4. Lymphoma cells need to be CD19 positive. In case of previous therapy with an anti-CD19 agent (including but not limited to blinatumomab, tafasitamab, loncastuximab tesirine), a new biopsy should be performed to confirm CD19 positivity. 5. The performance status of the patient as measured by the Eastern Cooperative Oncology Group (ECOG) performance scale should be 0 - 2 (ECOG performance status (PS):0-2). 6. Only adult patients will be eligible (patient age \>18 years old). Patients up to 80 years old will be considered to participate in the study assuming they fulfill all the other inclusion criteria 7. The creatinine clearance as measured by the Cockcroft-Gault equation should be 50 mL/min or better (CrCl ≥ 50 mL/min). 8. Unless the patient has a known Gilbert syndrome, the total Bilirubin should be less that 1.5 x upper limit of normal (ULN) and both the transaminases (ALT and AST) should be less than 2.5 x ULN. The only exception to this rule is lymphoma infiltration of the liver where values of total Bilirubin up to 3 x ULN and transaminases up to 5 x ULN will be allowed after communication with the Principal Investigator (P.I. or his/her designee) 9. The ejection fraction of the left ventricle as it is estimated on the Echocardiogram (preferably) or on the multigated acquisition (MUGA) scan should be at least 45% (LVEF ≥ 45%). 10. The oxygen saturation of oxyhemoglobin on room air as measured by pulse oximetry should be at least 94% (O2Sat ≥ 94%). If a technical problem (artifact) is suspected on pulse oximetry, arterial blood gases will be obtained for more accurate measurement. 11. On the day of screening and assuming there will be no other than the protocol therapy, the patient should have at least the following: 1. Absolute neutrophil count \>1000/microliter, 2. Hg\> 8 grams/ deciliter 3. Absolute lymphocyte count \>250/microliter 4. Platelet count \>75,000/microliter 12. Patient should not have a transfusion of packed red blood cells (PRBCs) or platelets or recei