Iberdomide Alone or in Combination With Dexamethasone for the Treatment of Intermediate- or High-Risk Smoldering Multiple Myeloma

PRIMARY OBJECTIVE:

I. To determine the overall response rate (ORR) of iberdomide hydrochloride (iberdomide) and iberdomide with dexamethasone in intermediate- and high-risk smoldering multiple myeloma (SMM).

SECONDARY OBJECTIVES:

I. To determine the 1- and 2- year progression free survival rates of patients receiving iberdomide with and without dexamethasone in intermediate-risk and high-risk smoldering myeloma.

II. To determine the time to progression, and overall survival of patients with intermediate- and high-risk smoldering myeloma receiving iberdomide with and without dexamethasone.

III. To study the risk of adverse hematologic and non-hematologic events observed in patients receiving iberdomide with and without dexamethasone for treatment of intermediate- and high-risk smoldering myeloma.

IV. To evaluate stem cell mobilization failure and early stem cell mobilization feasibility.

TERTIARY/EXPLORATORY OBJECTIVES:

I. To assess the effects of iberdomide on cereblon targets Aiolos and Ikaros in natural killer (NK)- and T- cells.

II. To measure the effect of iberdomide with and without dexamethasone on T-cell and NK-cell counts and activation.

III. To determine the prognostic impact of high-risk cytogenetic abnormalities on clinical outcomes.

IV. To assess minimal residual disease (MRD) on bone marrow samples in subjects who achieved a complete response (CR) or better and evaluate the correlation between MRD status and clinical outcome measures.

V. To assess the association between anti-tumor activity and immune cells in tumor and blood.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive iberdomide hydrochloride orally (PO) once daily (QD) on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive iberdomide hydrochloride PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.