Testing Teclistamab (TECVAYLI) in Combination With Iberdomide for Relapsed or Refractory Multiple Myeloma

PRIMARY OBJECTIVE: I. Estimate the recommended phase 2 dose (RP2D) of iberdomide in combination with teclistamab. SECONDARY OBJECTIVES: I. To evaluate the safety and toxicity profile of iberdomide in combination with teclistamab. II. To observe and record antitumor activity. CORRELATIVE OBJECTIVES: I. To evaluate the changes in the tumor immune microenvironment (exhausted T-cell phenotypes, percent T regulatory cells \[T regs\], T-cell activation) in peripheral blood and bone marrow caused by the addition of iberdomide to teclistamab and how they relate to minimal residual disease (MRD) status, responses rates and survival outcomes. II. To evaluate soluble B-cell maturation antigen (sBCMA) levels at baseline and how they correlate to response rates and survival outcomes in patients treated with teclistamab plus iberdomide. III. To identify the immunophenotypic and transcriptomic characterization of malignant plasma cells that are resistant to teclistamab and iberdomide. OUTLINE: This is a dose-escalation study of iberdomide in combination with teclistamab. Patients receive teclistamab subcutaneously (SC) on days 1, 4, 7, 15 and 22 for cycle 1 and days 1, 8, 15 and 22 for subsequent cycles. Patients also receive iberdomide orally (PO) once daily (QD) on days 1-21 for cycle 2 and beyond. Cycles repeat every 28 days for up to 4 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood and urine sample collection, bone marrow aspiration and biopsy and positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MR) throughout the trial. After completion of study treatment, patients are followed up every 3-6 months for up to 2 years.