Venetoclax and Tocilizumab for the Treatment of Patients With Relapsed or Refractory t(11;14) Multiple Myeloma

Eligibility Criteria

• * Subject must be \>= 18 years of age
• * Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of =\< 2
• * Diagnosis of multiple myeloma that requires treatment and has been previously treated with:
• * \>= 3 prior line of therapy. Have received treatment with a proteasome inhibitor, an immunomodulatory (IMiD) agent (e.g., thalidomide, lenalidomide, pomalidomide) and a CD38 monoclonal antibody
• * Have MM positive for t(11;14) translocation as determined by an analytically validated fluorescence in-situ hybridization (FISH) assay per the central laboratory testing
• * Subject must have had measurable disease at Screening, defined as any of the following:
• * Serum monoclonal protein \>= 1.0 g/dL (\>= 10 g/L) by protein electrophoresis, or
• * \>= 200 mg of monoclonal protein in the urine on 24-hour electrophoresis, or
• * Serum immunoglobulin free light chain (FLC) \>= 10 mg/dL provided serum FLC ratio is abnormal
• * Subjects with a history of autologous transplantation must have adequate peripheral blood counts as defined below, have recovered from any transplant related toxicity(s) and be \> 100 days post-autologous transplant (prior to first dose of study drug)
• * Absolute neutrophil count (ANC) \>= 1000/uL (Subject may use granulocyte colony-stimulating factor \[G-CSF\] to achieve ANC eligibility criteria)
• * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 1.5 x upper limit of normal range (ULN)
• * Calculated creatinine clearance \>= 30 mL/min using a modified Cockcroft- Gault calculation or a 24-hour urine collection for creatinine clearance
• * Platelet count \>= 75,000 cells/mm3 and independent of transfusion for 2 weeks
• * Hemoglobin \>= 8.0 g/dL, subjects may not receive blood transfusion within 1 week to achieve hemoglobin eligibility criteria per investigator discretion
• * Total bilirubin =\< 1.5 x ULN; subjects with Gilbert's syndrome may have bilirubin \> 1.5 x ULN
• * If female, subject must be:
• * Postmenopausal defined as:
• * Age \> 55 years with no menses for 24 or more months without an alternative medical cause
• * Age =\< 55 years with no menses for 24 or more months without an alternative medical cause
• * AND an follicle stimulating hormone (FSH) level \> 40 IU/L. OR
• * Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy) OR
• * A woman of childbearing potential (WOCP) practicing at least one protocol specified method of birth control starting at cycle 1 day 1 (or earlier) through at least 30 days after last dose of study drug
• * Females of childbearing potential (must have negative results for pregnancy test performed:
• * At screening, on a serum or urine sample obtained within 28 days prior to the first study drug administration,
• * Prior to dosing, on a urine sample obtained on the first day of study drug dosing, if it has been \> 7 days since obtaining the serum pregnancy test results
• * Females of non-childbearing potential (either postmenopausal or permanently surgically sterile as defined above) at screening do not require pregnancy testing
• * Must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures
• * Subject exhibits evidence of other clinically significant uncontrolled condition(s), including, but not limited to:
• * Acute infection within 14 days prior to first dose of study drug requiring antibiotic, antifungal, or antiviral therapy
• * Diagnosis of fever and neutropenia within 1 week prior to first dose of study drug
• * Subject has a cardiovascular disability status of New York Heart Association class \>= 3
• * Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular or hepatic disease within the last 6 months that, in the opinion of the investigator, would adversely affect his/her participation in the study
• * Subject has a history of other active malignancies other than multiple myeloma within the past 3 years prior to study entry, with the following exceptions:
• * Adequately treated in situ carcinoma of the cervix uteri,
• * Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin,
• * Localized prostate cancer Gleason grade 6 or lower AND with stable prostate specific antigen (PSA) levels off treatment
• * Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent
• * Known human immunodeficiency viral (HIV) infection
• * Active hepatitis B or C infection based on screening blood testing
• * Subject is receiving other ongoing anti-myeloma therapy
• * Subject has received any of the following within 7 days prior to the first dose of study drug:
• * Strong or moderate CYP3A inhibitors, or
• * Strong or moderate CYP3A inducers
• * Subject has received any of the following within 14 days prior to the first dose of study drug or has not recovered to less than a grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy: any anti-myeloma therapy including chemotherapy, radiotherapy, or investigational therapy, including targeted small molecule agents
• * Subject has received prior treatment with a BCL-2 family inhibitor
• * Subject is pregnant, parturient, or breastfeeding; deprived of freedom by judicial or administrative decision; hospitalized and unable to provide consent, or otherwise unable to provide consent
• * Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or star fruit within 3 days prior to the first dose of study drug
• * Subject has received immunization with live vaccine within 60 days of dosing
• * Recent corticosteroid therapy at a cumulative dose equivalent to \> 140 mg of prednisone or a single dose equivalent to \>= 40 mg of dexamethasone within 2 weeks prior to the first dose of study drug
• * Subject's decision to not divulge the race