Immunostart: Prephase Tafasitamab, Retifanlimab, and Rituximab (TRR), Followed by TRR With Standard Therapy for Previously Untreated Diffuse Large B-Cell Lymphoma
This phase I/II trial tests the safety of tafasitamab, retifanlimab, and rituximab (TRR) as a prephase treatment and in combination with standard therapy consisting off cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or polatuzumab vedotin, cyclophosphamide, doxorubicin, and prednisone (PolaCHP) in patients with untreated diffuse large B-cell lymphoma. Tafasitamab, retifanlimab, and rituximab are monoclonal antibodies. Tafasitamab binds to a protein called CD19, which is found on B-cells (a type of white blood cell) and some types of cancer cells. Rituximab binds to a protein called CD20, which is also found on B-cells and some cancer cells. These monoclonal antibodies may help the immune system kill cancer cells. Immunotherapy with other monoclonal antibodies, such as retifanlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as CHOP and PolaCHP, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving TRR in combination with CHOP or PolaCHP may kill more cancer cells.
• Patients with previously untreated diffuse large B cell lymphoma or grade 3B follicular lymphoma (of any stage). Patients may have de novo DLBCL, and /or any of the following:
‣ Composite lymphomas, which include both diffuse DLBCL and another histology (most commonly follicular lymphoma) in the same lymph node,
⁃ Transformed lymphoma with DLBCL histology, as long as the patient has not received prior therapy for lymphoma,
⁃ Discordant presentations, such as DLBCL in a lymph node and low-grade lymphoma such as follicular lymphoma in the bone marrow, and
⁃ High grade B-cell lymphoma (including double hit lymphomas or high grade B-cell lymphoma-not otherwise specified \[HGBCL-NOS\]) is permitted if the patient is not eligible for or declines intensive therapy
• Be willing and able to provide written informed consent/assent for the trial
• Be \>= 18 years of age on day of signing informed consent
• Have measurable disease, including at least 1 nodal site measuring 1.5 cm or 1 extranodal site measuring 1.0 cm in longest dimension on computed tomography (CT) or fludeoxyglucose F-18-positron emission tomography (FDG-PET)
• Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale (PS)
• Absolute neutrophil count (ANC) \>= 1,000/mcL except in case of marrow infiltration by lymphoma
• Platelets \>= 75,000/mcL except in cases of marrow infiltration by lymphoma
• Serum creatinine clearance (CrCl) must be \>= 30 mL/minute either measured or calculated using a standard Cockcroft and Gault formula
‣ Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =\< 1.5 x upper limit of normal (ULN) unless secondary to Gilbert's syndrome or documented liver involvement by lymphoma. Patients with Gilbert's syndrome or documented liver involvement by lymphoma may be included if their total bilirubin is =\< 5 x ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN OR =\< 5 x ULN for subjects with liver metastases
• Left ventricular ejection fraction of \>= 45%, assessed by echocardiography or cardiac multi-gated acquisition (MUGA) scan
• Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential should be willing to use 2 methods of birth control, be surgically sterile, or abstain from heterosexual activity starting with the first dose of study therapy and for 180 days after the last dose of study medication. Female subjects of childbearing potential must also agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the trial and for 180 days after receiving the last dose of study therapy. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year
• Male subjects should agree to use 2 methods of contraception starting with the first dose of study therapy and for 180 days after the last dose of study therapy