This study is being done to determine the safety, efficacy and tolerability of a single 50 mCi dose of 131I-Apamistamab given prior to FDA approved (commercially available) infusion in patients with Relapsed or refractory (R/R) non-Hodgkin lymphoma.

This is an open-label single-cohort multi-institutional study of 131I-Apamistamab followed by CAR-T cell therapy for patients with (R/R) DLBCL. Patients will receive a 50 mCi single planned 131I-Apamistamab dose prior to CAR-T cell infusion for lymphodepleting conditioning. There will be a 6-patient safety run-in to assess safety.

Inclusion Criteria:

1. Patients with diffuse large B-cell lymphoma (de novo or DLBCL transformed from an indolent lymphoma (follicular lymphoma, chronic lymphocytic leukemia [Richter syndrome]) or high-grade B-cell lymphoma (HGBL): ("DLBCL patients")

   • Defined as relapsed or refractory DLBCL or high-grade B-cell lymphoma (HGBL) following at least one or more prior chemoimmunotherapy regimen (with at least one course including an anthracycline and CD20-directed therapy) following diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent lymphoma and requiring further treatment and deemed to be candidates for standard of care CAR-T therapy. This includes patients with primary refractory disease (failure to achieve complete response (CR) to first-line therapy), relapsed disease within 12 months of first line chemoimmunotherapy or relapsed/refractory disease after 2 or more prior lines of systemic therapy.
   • Relapsed or refractory disease must be confirmed with a repeat biopsy within the last 12 months.

2. Age ≥ 18 years of age

3. Creatinine clearance ≥50 mL/min as calculated by the Cockroft-Gault formula.

4. Total bilirubin ≤1.5x upper limit of normal , AST and ALT ≤3x upper limit of normal (ULN), unless liver dysfunction is thought to be related to underlying malignancy or secondary to Gilbert's disease in which case the direct bilirubin should be ≤3.0 mg/dL, and AST and ALT ≤5x ULN.

5. Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air or per institutional guidelines.

6. Thyroid function tests (TSH, FT4) ≤2x upper limit of normal (ULN)

7. Adequate bone marrow function meeting the following criteria as defined below, without requiring blood product or granulocyte-colony stimulating factor support in the 7 days prior to screening and start of 131I-Apamistamab treatment.

   1. Absolute neutrophil count ≥1.0k/µL,
   2. Platelets ≥50k/µL,
   3. Hemoglobin ≥8g/dL.

8. Performance status: ECOG performance status 0-2.

9. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, and/or abstinence) prior to study entry, and for the duration of study treatment, and for 30 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

   A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

   • Has not undergone a hysterectomy or bilateral oophorectomy; or
   • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

10. Ability to understand and the willingness to sign a written informed consent.

11. For patients undergoing bridging therapy after leukapheresis and prior to 131I-Apamistamab infusion a repeat PET or CT scan will be performed 10-14 days prior to the 131I-Apamistamab infusion. They will also be required to meet inclusion criteria number 1 and 7 above within 10-14 days prior to the planned infusion of 131I-Apamistamab. This will be considered eligibility Screening 2 and will be approved by the Sponsor-Investigator.

Exclusion Criteria:

1. Pregnant or lactating patients.

2. Impaired cardiac function (LVEF <40%) as assessed by echocardiogram or MUGA scan.

3. Patients with active graft versus host disease following allogeneic hematopoietic cell transplantation requiring systemic T-cell suppressive therapy are ineligible.

4. Patients with active autoimmune disease requiring systemic T-cell suppressive therapy are ineligible.

5. Patients with the following cardiac conditions will be excluded:

   1. New York Heart Association (NYHA) stage III or IV congestive heart failure
   2. Myocardial infarction ≤6 months prior to enrollment
   3. Any history of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration.

6. Have current or prior positive test results for human immunodeficiency virus (HIV) or hepatitis B (HBV) or C (HCV), with the following exceptions:

   1. Patients who have positive HBV test results due to having been previously vaccinated against hepatitis B, as evidenced by negative hepatitis B surface antigen (HbsAg), negative anti- hepatitis B core protein (HBc) and positive antibody to the HbsAg (anti-HBs) are not excluded.
   2. Patients who have antibodies to HCV or who have hepatitis B core antibody, with undetectable viremia by PCR, and with adequate organ function as defined in the protocol, are not excluded.

7. Patients with uncontrolled systemic fungal, bacterial, viral, or other infections are ineligible.

8. Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of skin.

9. Patients with history or presence of clinically significant neurological disorders such as epilepsy, generalized seizure disorder, severe brain injuries are ineligible.

10. Any other issue which, in the opinion of the treating physician, would make the patient ineligible for the study.

11. Patients with circulating human anti-mouse antibodies (HAMA) to BC8. The results of HAMA testing will need to be available prior to 131I-Apamistamab infusion.

12. Patients with prior history of treatment with radiopharmaceuticals for lymphoma treatment indication.

13. Patients with QTcF >470mSec on EKG