The following criteria is provided for health care professionals.

Inclusion Criteria:

• Patient must have relapsed or refractory myeloma that fits or did fit International Myeloma Working Group (IMWG) diagnostic criteria for symptomatic myeloma (although new or worsening end organ damage is not required to be eligible) as defined below:
  • Presence of clonal bone marrow plasma cells
  • Presence of serum and/or urinary measurable monoclonal protein or light chains
  • Evidence of any end organ damage criteria listed below (at any time) attributed to the patient's myeloma:
    • Hypercalcemia: serum calcium > 11.5 mg/dL or
    • Renal insufficiency: serum creatinine > 2 mg/dL
    • Anemia > 2 g/dL below the lower limit of normal or a hemoglobin value < 10 g/dL
    • Bone lesions: lytic lesions, severe osteopenia or pathologic fractures
• Patients must have measurable disease defined as any of the following:
  • Serum monoclonal protein >= 500 mg/dL by protein electrophoresis
  • > 200 mg of monoclonal protein in the urine on screening 24-hour electrophoresis
  • Serum immunoglobulin free light chain >= 100 mg/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Patients must have received an immunomodulatory drug (IMiD) and proteasome inhibitor, and must be progressing; prior autologous and/or allogeneic transplant is permitted although transplant must have occurred greater than 90 days prior to registration
• Both men and women of all races and ethnic groups are eligible for this study
• In the expansion cohort only, 3 patients can have progressed while receiving a carfilzomib-containing regimen in the past
• Prior radiation is permitted; however, at least 2 weeks must have elapsed since the completion of prior radiation therapy and patients must have recovered from all radiation-associated toxicities to no greater than grade 1 at the time of registration
• Patients with expected carfilzomib sensitive disease, Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) is required for eligibility; those patients with expected carfilzomib sensitive disease with lower performance status based solely on bone pain secondary to multiple myeloma are eligible; patients with myeloma-related pain or other disease-related morbidities equivalent to > grade 2 toxicity or ECOG performance status > 1 expected to be carfilzomib refractory are ineligible
• Absolute neutrophil count (ANC) >= 1000/uL
• Platelet count >= 50,000/uL
• Total bilirubin < 1.5 mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x the institutional upper limit of normal
• Ability to understand and the willingness to sign a written informed consent document
• Patients must be able to avoid direct contact with pregnant or nursing women, infants and immunocompromised individuals during the days of reolysin treatment and for two days after
• Patients must not have known human immunodeficiency virus (HIV) infection or active hepatitis B or C infections
• Systolic cardiac function will be assessed at screening if clinically indicated by history and physical; only patients with left ventricular ejection fraction (LVEF) >= 50% will be eligible for enrollment
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL prior to starting therapy and prior to beginning another cycle (if applicable)
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting 28 days prior to starting the study until at least 90 days following discontinuation of the trial therapy; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• The patient must be willing to comply with fertility requirements as below:
  • Male patients must agree to use an adequate method of contraception for the duration of the study and for 90 days afterwards
  • Female patients must be either postmenopausal, free from menses >= 2 years, surgically sterilized, willing to use two adequate barrier methods of contraception to prevent pregnancy, or agree to abstain from heterosexual activity starting with screening and for 90 days afterwards
  • Patients must agree not to donate blood, sperm/ova during the course of taking protocol therapy and for at least 4 weeks after stopping treatment

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study; patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg by mouth daily or its equivalent) for symptom management and comorbid conditions; doses of corticosteroid should be stable for at least 7 days prior to study treatment
• Patients who are receiving any other therapeutic investigational agents
• Patients previously treated on clinical trial with reolysin
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the preceding 6 months, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued
• Patients with a "currently active" second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to < 1 year, or confound data interpretation
• Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein), and skin changes (POEMS) syndrome
• Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug