Low Dose Radiation as Bridging Therapy in Relapsed B-Cell Non-Hodgkin Lymphoma

This is a pilot study to evaluate the feasibility of low-dose radiation therapy in the bridging period between chimeric antigen receptor (CAR) T-cell collection, manufacturing, and infusion (vein-to-vein) in patients with relapsed and refractory aggressive B-cell lymphoma.

Emerging cellular immunotherapies including CAR T-cell therapy have produced remarkable outcomes for this population. The Food and Drug Administration (FDA) has recently approved lisocabtagene maraleucel (liso-cel) for the management of people with relapsed and refractory B-cell lymphoma. Unfortunately, many patients undergoing liso-cel infusion will suffer progression or relapse with devastating consequences. The object of this study is to identify a novel means to enhance liso-cel activity to improve overall outcomes. The investigators hypothesize that the addition of radiation therapy targeting selected sites as bridging therapy prior to lymphodepleting chemotherapy and liso-cel infusion will be effective at improving responses for patients with relapsed and refractory B-cell lymphoma.

Results from this study will provide key justification to expand this therapeutic approach into a larger phase II clinical trial powered to examine the efficacy of this approach.

Inclusion criteria

• Biopsy-proven relapsed or progressive diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, grade 3B follicular lymphoma, or DLBCL arising from indolent lymphoma meeting an FDA-approved (Food and Drug Administration-approved) indication for liso-cel infusion
• Presence of disease on imaging including at least one disease site safe for radiation as determined by treating radiation oncologist
• Willingness to participate in clinical trial and provide informed consent
• Adequate organ function as assessed by standard institution protocols and United States (US) prescribing information label for comorbidities, heart, and lung function to undergo FDA-approved CAR T-cell therapy as determined by institution
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Age 19 years or older, there is no upper limit to the age

Exclusion criteria

• Subject is unsafe for radiation therapy as determined by investigator and/or radiation oncologist
• Diagnosis is primary central nervous system (CNS) lymphoma (secondary CNS lymphoma with additional systemic site is allowed)
• Requirement for concurrent high dose methotrexate
• Secondary active malignancy that has not been in remission for at least 2 years. This excludes non-melanoma skin cancer, definitively treated stage 1 solid tumor with low risk or recurrence, and curatively treated localized prostate cancer.
• Pregnant or nursing women
• Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as determined by investigator
• Unwillingness to follow procedures required in the protocol
• Inadequate organ or hematologic conditions that prohibit the use of lymphodepleting chemotherapy
• Use of lymphoma-directed therapy within 14 days of T-cell pheresis