External Beam Radiation Therapy in Combination With Talquetamab for the Treatment of Multiple Myeloma Patients With Extramedullary Disease

Inclusion Criteria

• •Documented informed consent of the participant and/or legally authorized representative
• •* Assent, when appropriate, will be obtained per institutional guidelines
• •Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• •* If unavailable, exceptions may be granted with study principal investigator (PI) approval
• •Age: ≥ 18 years
• •Karnofsky performance status (KPS) ≥ 60%
• •Diagnosis of multiple myeloma with extramedullary disease (EMD). EMD is defined as soft-tissue plasmacytomas NOT arising from skeletal lesions (i.e., the EMD is not contiguous with any bone/bony lesion)
• •Measurable systemic disease defined as serum M-spike ≥ 0.5 g/dl, 24-hour urine M-spike ≥ 200 mg/24 hours (hr), involved serum free light chain (FLC) ≥ 10 mg/dl with abnormal FLC ratio, and/or a non-target plasmacytoma ≥ 2 cm in a single diameter (NOTE: Non-target plasmacytoma must not be included in the EMD-EBRT field)
• •At least one site of EMD must have an indication for palliative radiation per the treating clinicians (e.g., including but not limited to pain, asymmetry, discomfort, threatening to vital structure, etc.)
• •Target EMD site must be encompassed by one radiation field per treating radiation oncologist
• •Subject must have received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody
• •Fully recovered from the acute non-hematologic toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
• •Prior antitumor therapy must have been completed prior to enrollment as follows:
• •* ≥ 2 weeks for prior external beam radiotherapy (XRT) to non-target site
• •* ≥ 21 days for cytotoxic chemotherapy (systemic or intrathecal)
• •* ≥ 28 days for prior adoptive cell therapy or T-cell redirecting therapies
• •* ≥ 4 weeks or 5 half-lives (whichever is shorter) for other myeloma therapies
• •Absolute neutrophil count (ANC) ≥ 1,000/mm\^3 (prior growth factor support is permitted but must be without support for 7 days for granulocyte colony-stimulating factor \[G-CSF\] or granulocyte-macrophage colony-stimulating factor \[GM-CSF\] and for 14 days for pegylated GCSF before the laboratory test)
• •* Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• •Platelets ≥ 50,000/mm\^3
• •* NOTE: No transfusion support or thrombopoietin receptor agonist within 7 days before laboratory test
• •* Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• •Hemoglobin ≥ 8g/dL
• •* NOTE: No transfusion support or erythropoietin use within 7 days before the laboratory test
• •* Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• •Total bilirubin ≤ 2.0 X upper limit of normal (ULN) (unless has congenital bilirubinemia such as Gilbert's disease, in which case ≤ 1.5 × ULN is required)
• •* Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• •Aspartate aminotransferase (AST) ≤ 2.5 x ULN
• •* Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• •Alanine aminotransferase (ALT) ≤ 2.5 x ULN
• •* Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• •Creatinine clearance of ≥ 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula
• •* Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• •Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
• •* If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• •* Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• •Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of talquetamab
• •* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)