This study will recruit patients currently receiving either lenalidomide or pomalidomide whose disease is relapsing. This is a dose escalation study and the aim is to determine the maximum tolerated dose (MTD) of REOLYSIN® that can be given in combination with lenalidomide or pomalidomide. The study will also investigate the safety, side effects and effectiveness of this treatment combination. Pomalidomide and lenalidomide will be evaluated separately as two separate groups.

Inclusion Criteria:

• Diagnosed with symptomatic multiple myeloma (according to IMWG 2014 criteria)
• Evaluable disease by modified IMWG criteria (i.e. by abnormal serum M protein, urinary M protein or serum free light chain assays)
• Currently receiving either lenalidomide or pomalidomide therapy, alone or in combination with other myeloma therapy, with evidence of serological or clinical disease progression as defined by IMWG criteria (2011)
• Life expectancy of ≥ 3 months
• ECOG performance status of ≤2
• Required laboratory values within 14 days prior to dose allocation:
• Absolute neutrophil count ≥ 1.0 x10^9 /L. (growth factor support is not permitted)
• Platelet count ≥ 70 x 10^9/L. (platelet support is not permitted; platelets < 70 but ≥ 25 acceptable if bone marrow is > 50% infiltrated by MM)
• Haemoglobin ≥ 8 g/dL. Blood support is permitted
• Serum bilirubin ≤ 2 x upper limit of normal (ULN)
• ALT or AST ≤ 2.5 x ULN
• Serum creatinine ≤ 2 x ULN
• Corrected calcium ≤ 2.8 mmol/l
• Negative HIV and viral (B and C) hepatitis test result within 14 days prior to dose allocation
• Able to give informed consent and willing to follow trial protocol
• Aged 18 years or over
• All participants must agree to follow the Celgene Pregnancy Prevention Programme (PPP) and participate in the counselling associated with this:
• Females of childbearing potential (FCBP) must agree to utilise two reliable forms of contraception simultaneously or practice complete abstinence for at least for 28 days prior to starting trial treatment, during the trial and for at least 28 days after trial treatment discontinuation, and even in case of dose interruption, and must agree to Celgene PPP pregnancy testing during this timeframe
• Females must agree to abstain from breastfeeding during trial participation and 28 days after trial drug discontinuation
• Males must agree to use a latex condom during any sexual contact with FCBP (or must practice complete abstinence) during the trial, including during dose interruptions and for 28 days following discontinuation from this trial even if he has undergone a successful vasectomy
• Males must also agree to refrain from donating semen or sperm while on pomalidomide including during any dose interruptions and for 28 days after discontinuation from this trial
• All participants must agree to refrain from donating blood while on trial drug including during dose interruptions and for 28 days after discontinuation from this trial

Exclusion Criteria:

• Non-secretory multiple myeloma
• Pregnant (positive pregnancy test) in line with the Celgene Pregnancy Prevention Programme or breast feeding
• Previous anti-tumour therapies including experimental agents, other than lenalidomide or pomalidomide, within 28 days of the start of protocol treatment. Steroid therapy is permitted, but must be stopped 48 hours prior to cycle 1 day 1
• Concurrent or previous malignancies (<12 months post end of treatment) at other sites, with the exception of appropriately treated localised epithelial skin or cervical cancer, or incidental histologic findings of prostate cancer (TNM stage T1a or 1b). Participants with histories (≥12 months) of other tumours, in remission and not currently on therapy, may be entered
• System corticosteroid therapy for comorbidities (i.e. medical conditions other than multiple myeloma) that cannot be stopped for the duration of the trial. Topical corticosteroid therapy is not an exclusion criterion.
• Any history of known hypersensitivity to any of the trial medications or excipients
• Active symptomatic fungal, bacterial, and/or viral infection
• Poorly controlled or serious medical or psychiatric illness that, in the Investigator's opinion, is likely to interfere with participation and/or compliance in this clinical trial
• Patients with significant cardiovascular disease (e.g. history of congestive heart failure requiring therapy (≥ NYHA Class III), presence of severe valvular heart disease, presence of an atrial or ventricular arrhythmia requiring treatment, uncontrolled hypertension, or history of QTc abnormalities)
• Radiotherapy or major surgery within 4 weeks prior to registration
• Greater than or equal to grade 2 neuropathy, with or without pain