Radiation Post-CAR T in Refractory Lymphoma

Inclusion Criteria:

* Patients must be able to undergo biopsy. Biopsy will be obtained for patients to exclude possibility of false negative residual FDG avidity on PET/CT that is not substantially increased relative to pre-CAR-T PET/CT. Exceptions are allowed for patients who have clearly progressive disease for whom delaying radiation therapy to obtain a biopsy may worsen outcome (such as cases of cord compression), and for patients for whom the risks of biopsy are high (such as patients with evidence for CNS involvement).
* Biopsy-confirmed refractory disease within 30-90 days following commercial axicabtagene ciloleucel or tisagenlecleucel therapy for a hematologic malignancy (these include relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma). Of note, 'refractory' refers to patients who had early refractory disease after CAR-T cell therapy and not to patients who have received CAR-T for refractory disease, but had complete response to CAR-T cell therapy.
* At least 1 measurable lesion according to the Lugano criteria1. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
* The following criteria pertain to pattern of progression:

  * Patients may have one refractory lesion without other residual or progressive disease as per PET/CT
  * Patients may have more than one refractory lesion, but with evidence for at least partial response of at least one other lesion as per PET/CT
  * Patients with more than one site of refractory disease without evidence for at least partial response of at least one other lesion are eligible if they are:

    * A. Symptomatic from a refractory lesion (such as cord compression or focal pain) or
    * B. Have disease that can locally affect the spinal canal or brain if left untreated.
* Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia and prolonged cytopenias that are not expected to worsen during RT) if there is concern for overlap of anticipated radiation-related toxicity and toxicity from prior therapy due to where the RT field is located.
* Age 18 or older
* Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Any medical condition likely to interfere with assessment of safety or efficacy of RT
* Patients with more than one site of disease without any evidence for response to CAR T cell therapy who are not focally symptomatic due to progressive disease or do not have disease that can locally affect the spinal canal or brain if left untreated
* Women of child-bearing potential who are pregnant because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential.
* In the investigators judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.