Epcoritamab as Consolidative Therapy for Waldenstr(SqrRoot)(Delta)m Macroglobulinemia (WM) Treated With a Bruton Tyrosine Kinase Inhibitor (BTKi)

Background: Waldenstrom macroglobulinemia (WM) is a type of blood cancer. It causes the blood to get thicker, which slows circulation and makes it harder to carry oxygen and other substances around the body. WM is treated with drugs called Bruton tyrosine kinase inhibitors (BTKi). But WM never goes away completely, and sometimes it gets worse despite treatment. Objective: To test a new drug (epcoritamab) in people with WM. Eligibility: People aged 18 years or older who have WM. They must have been taking a BTKi for a year or more. Design: Participants will be screened. They will have blood and urine tests. They will have imaging scans and a test of their heart function. They may have a bone marrow biopsy: A large needle will be used to remove a sample of the soft tissue and fluids from inside the hip bone. Epcoritamab is injected under the skin, normally on the lower belly or thigh. Participants will be treated in 28-day cycles. They will have 12 treatment cycles. During the first cycle, they will come to the clinic to get an injection once a week for 4 weeks. After that, they will get 1 injection on the first day of each cycle. Blood tests and imaging scans will be repeated at study visits. A saliva sample will be taken for genetic testing. Participants will also continue their normal treatment with BTKi. After their last treatment with the study drug, participants will have 5 follow-up visits in 6 months. Tests, including a bone marrow biopsy, may be repeated. Follow-up visits will continue every 6 months for 3 (Omega) years or more.