PRIMARY OBJECTIVES:~I. To assess the maximum tolerated dose (MTD) of iberdomide in combination with daratumumab, bortezomib, and dexamethasone. (Phase 1 [Dose Confirmation Cohort]) II. To determine the complete response rate as best response during induction therapy with (1) iberdomide, daratumumab, bortezomib and dexamethasone (IberDVd) when used as initial therapy in patients with previously untreated symptomatic multiple myeloma. (Phase 2)~SECONDARY OBJECTIVES:~I. To assess the overall response rate (ORR) and very good partial response (VGPR) rate of iberdomide in combination with daratumumab, bortezomib and dexamethasone. (Phase 2) II. To assess the progression free survival and overall survival among patients with previously untreated symptomatic multiple myeloma following treatment with iberdomide in combination with daratumumab, bortezomib and dexamethasone. (Phase 2) III. To assess the time to response (defined as the time between the date of first dose and the first documented evidence of a partial response or better) following treatment with iberdomide in combination with daratumumab, bortezomib and dexamethasone in patients with previously untreated symptomatic multiple myeloma (MM). (Phase 2) IV. To identify the proportion of patients with measurable residual disease (MRD) negative complete response (as measured by the next-generation flow cytometry, sensitivity 10-5) at the end of cycles 24 and 36 during the deescalated phase of iberdomide monotherapy administration. (Phase 2) V. To describe the toxicities associated with iberdomide in combination with daratumumab, bortezomib and dexamethasone in patients with previously untreated symptomatic MM and toxicities associated with dose attenuated iberdomide monotherapy administered from cycles 13 through 36. (Phase 2)~CORRELATIVE RESEARCH OBJECTIVES:~I. Examine the proportion of next generation flow cytometry assessed MRD negative complete response following induction therapy with the combination of iberdomide in combination with daratumumab, bortezomib and dexamethasone. (Phase 2) II. Examine the proportion of sustained MRD negative complete response following 6 months after attaining complete response (CR) and at the end of cycles 24 and 36. (Phase 2)~OUTLINE: This is a phase I, dose-escalation study of iberdomide followed by a phase II study.~INDUCTION PHASE: Patients receive iberdomide orally (PO) once daily (QD) on days 1-21, bortezomib subcutaneously (SC) on days, 1, 8, 15, and 22, and dexamethasone PO on days 1, 8, 15, 22. Patients also receive daratumumab SC on days 1, 8, 15, 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.~CYCLES 13-36 CYCLES: Patients receive iberdomide PO QD on days 1-21. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 30 days and then every 6 months for 3 years.
This phase I/II trial studies the side effects and best dose of iberdomide and how well it works in combination with daratumumab, bortezomib, and dexamethasone in treating patients with newly diagnosed multiple myeloma. Immunotherapy with iberdomide, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Daratumumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving iberdomide in combination with daratumumab, bortezomib, and dexamethasone may kill more cancer cells in patients with newly diagnosed multiple myeloma.