Inclusion Criteria:
* Eastern Cooperative Oncology Group Performance Status of 0 to 2
* Not eligible for stem cell/bone marrow transplant or have refused stem cell/bone marrow transplant or have relapsed after autologous or allogeneic stem cell/bone marrow transplant
* Eligible for and agree to BM aspirate prior to treatment start
* Measurable disease M component in serum (≥ 0.5 g/dL) and/or urine (≥ 0.2 g excreted in a 24 hour collection sample)
* Must have received at least 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or those who are double refractory to a PI and an immunomodulatory agent and have demonstrated disease progression (DP) on or within 60 days of completion of the last therapy; participants previously treated with an alkylating agent, in addition to an IMiD or proteasome inhibitor, are allowed to enroll in the trial
* Participants must have adequate liver, kidney, and bone morrow function
* Participants with a history of chronic heart failure must have cardiac ECHO indicating left ventricular ejection fraction (LVEF) ≥ 45% within 21 days prior to first dose of study drug
* Participants in the combination therapy arms must be eligible to receive pomalidomide/dexamethasone, bortezomib/dexamethasone or lenalidomide/dexamethasone or other approved agents per current prescribing information for MM.
* Participants who will receive combination therapy with Pomalidomide/Dexamethasone must have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy
Exclusion Criteria:
* Received anti-cancer therapy including chemotherapy, immunotherapy, radiation, biologic, any investigational therapy or herbal therapy within a period of 21 days prior to the first dose of ABBV-838, and have unresolved toxicities ≥ grade 2
* Concurrent metastatic solid tumors
* Non-Measurable M Protein (serum or urine) and measurable sFLC (\< 100 mg/mL)
* Major surgery within 21 days prior to the first dose of ABBV-838
* Clinically significant uncontrolled condition(s) including but not limited to the following:
Grade ≥ 3 peripheral neuropathy or grade 2 peripheral neuropathy with pain Uncontrolled hypercalcemia Active uncontrolled infection Symptomatic congestive heart failure Unstable angina pectoris or cardiac arrhythmia Psychiatric illness/social situation that would limit compliance with the study
* Major immunologic reaction to any IgG containing agent or auristatin based agent
* Participants who are taking strong CYP3A4 inhibitors
* Positive for HIV (Human Immunodeficiency Virus) or with active hepatitis B and/or C
* Corneal pathology that would limit evaluation of loss in visual acuity associated with corneal deposits.
* Prior exposure to pomalidomide for subjects enrolling in the pomalidomide/dexamethasone combination arm.
