Epcoritamab and Lenalidomide in Treating Patients With Refractory or Relapsed Immunodeficiency-Related Large B-Cell Lymphoma

PRIMARY OBJECTIVE: I. To evaluate the six-month best response of complete response (CR) rate for the combination of epcoritamab-lenalidomide in chemotherapy ineligible patients with primary refractory or relapsed immunodeficiency-related large B-cell lymphoma. SECONDARY OBJECTIVES: I. To evaluate the objective response rate (ORR), partial response (PR) and CR rates at 3 (cycle \[C\] 4 day \[D\]1), 6 (C7D1), 12 (30 days post C12), 18 and 24 months for patients on combination epcoritamab-lenalidomide. II. To assess duration of response (DoR) at 6 (C7D1),12 (30 days post D12), 18 and 24 months for patients on combination epcoritamab-lenalidomide. III. To assess progression free survival (PFS) with 12,18 and 24 months of follow-up for patients on combination epcoritamab-lenalidomide. IV. To assess overall survival (OS) with 12, 8 and 24 months of follow-up for patients on combination epcoritamab-lenalidomide. V. To assess the safety and toxicity of combination epcoritamab-lenalidomide. EXPLORATORY OBJECTIVES: I. To assess changes in immune-cell subsets with utilization of epcoritamab-lenalidomide. II. To evaluate T cell polyfunctionality with the administration of combination epcoritamab-lenalidomide over time. III. To gain more insights into the phenotype and functional state of different circulating immune cell subsets. IV. To measure disease-specific symptoms and/or treatment-related concerns in patients treated with combination therapy using Functional Assessment of Cancer Therapy - Lymphoma (FACTLym) European Organization for Research and Treatment of Cancer (EORTC) and Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires. OUTLINE: Patients will receive epcoritamab subcutaneously (SC) weekly during cycle 1 and on days 1, 8, 15, and 22 of cycles 2-3, and day 1 of cycles 4-12. Patients will also receive lenalidomide orally (PO) on days 1-21 of each cycle. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients will undergo positron emission tomography (PET)/computed tomography (CT) and collection of blood samples throughout the study and may undergo magnetic resonance imaging (MRI) during screening. After completion of study treatment, patients will be followed up at 30 days, then at 12, 18 and 24 months.