Immunomodulatory Drugs (Lenalidomide With or Without Pomalidomide) in Combination With a Corticosteroid Drug (Dexamethasone) for the Treatment of Multiple Myeloma

PRIMARY OBJECTIVE: I. To determine response rates (\>= partial response \[PR\]) of prospectively treated multiple myeloma (MM) patients with one cycle of therapy containing a combination of an immunomodulator and dexamethasone. SECONDARY OBJECTIVE: I. To compare response rates of MM among African-Americans (AA) and white patients to a combination of an immunomodulator and dexamethasone. II. To establish correlation of biomarkers in treated MM patients with the combination of an immunomodulator and dexamethasone to the depth of hematological response observed in new or previously treated patients. CORRELATIVE OBJECTIVE: I. To identify biomarkers that predict response rates of untreated smoldering MM and MM patients to a combination of an immunomodulator and dexamethasone. OUTLINE: Patients are assigned to 1 of 4 cohorts. COHORT A: Patients with smoldering multiple myeloma receive lenalidomide orally (PO) once daily (QD) alone on days 1-14 OR in combination with dexamethasone PO QD on days 1, 8 and 15. Treatment for cycle 1 continues for 21 days in the absence of disease progression or unacceptable toxicity. Patients then receive lenalidomide PO QD on days 1-21 alone or in combination with dexamethasone PO QD on days 1, 8, 15, and 22, or in combination with another drug. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. COHORT B: Patients with newly diagnosed multiple myeloma receive treatment as in Cohort A. COHORT C: Patients with relapsed or refractory multiple myeloma receive lenalidomide PO QD on days 1-14 in combination with dexamethasone PO QD on days 1, 8 and 15 OR pomalidomide PO QD on days 1-21 in combination with dexamethasone PO QD on days 1, 8 and 15. Treatment for cycle 1 continues for 21 days in the absence of disease progression or unacceptable toxicity. Patients then receive lenalidomide PO QD on days 1-21 in combination with dexamethasone PO QD on days 1, 8, 15, and 22 OR pomalidomide PO QD on days 1-21 in combination with dexamethasone PO QD on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. COHORT D: Patients with relapsed multiple myeloma after lenalidomide maintenance receive treatment as in Cohort C. After completion of study treatment, patients are followed up within 7 days.