'Re-Priming' RT After Incomplete Response to CAR-T in R/R NHL

Inclusion Criteria:

1. Age ≥ 18 years.
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening
3. Biopsy-proven histological high-grade non-Hodgkin lymphoma, such as diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma.
4. Prior treatment with any CD19-directed CAR T-cell therapy, such as tisagenlecleucel (tisa-cel, Kymriah), axicabtagene ciloleucel (axi-cel, Yescarta), or lisocabtagene maraleucel (liso-cel).
5. Incomplete response noted on day 30 PET post-CAR-T, defined as not achieving CR per Lugano 2014 classification
6. Ability to understand and the willingness to sign a written informed consent
7. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 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.

7.1 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).

Exclusion Criteria:

1. Prior "definitive" radiation therapy (40-50 Gy EQD2 with an α/β of 10) to one or more sites of incomplete response as noted on day 30 post-CAR-T PET/CT scan within the past one year. Prior "palliative" radiation therapy (\<40 Gy EQD2) permissible at discretion of treating physician.
2. Intracranial site of incomplete response as noted on day 30 post-CAR-T PET/CT scan or any active central nervous system involvement by malignancy.
3. Active grade 3 or higher CRS or neurotoxicity related to CAR-T.
4. Patients with prior history of auto-immune disease or other contraindication to RT.
5. Patients with life expectancy \< 3 months.
6. Psychiatric illness/social situations that would limit compliance with study requirements.
7. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.