The subject has received systemic dexamethasone continuously at a dose > mg/day for weeks prior to the date of the screening assessment Receive dexamethasone equivalent dose /= three days prior to Day ; Dexamethasone equivalent dose > mg per day; Requires treatment with high dose systemic corticosteroids defined as dexamethasone > mg/day or bioequivalent within at least days of initiating therapy < mg dexamethasone daily (or equivalent if on another corticosteroid) at time of start of therapy; patients on a steroid taper post-surgery and are anticipated to be on < mg at time of chemoradiation initiation will be eligible to consent but to initiate treatment on trial, the participant must be on < mg or equivalent of steroids otherwise participate will be deemed a screen fail and be replaced Requires treatment with high dose systemic corticosteroids defined as dexamethasone > mg/day or bioequivalent within days of initiating therapy Treatment with high dose systemic corticosteroids defined as dexamethasone > mg/day or bioequivalent within days of initiating therapy Treatment with high dose systemic corticosteroids defined as dexamethasone > mg/day or bioequivalent within days of initiating therapy The patient must be either off systemic steroids or be on stable dose of dexamethasone (max . mg/kg/day; maximum mg/day) at time of enrollment EXCLUSION CRITERIA FOR STRATUM C: Patients may not be on immunosuppressive therapy, including corticosteroids (with the exception of physiologic replacement, defined as =< . mg/m^/day dexamethasone equivalent) at time of enrollment; however, patients who require intermittent use of bronchodilators or local steroid injections will not be excluded from the study Corticosteroids use exceeding a cumulative dose of mg of dexamethasone during screening Research participant must not require more than mg three times daily TID of dexamethasone on the day of PBMC collection. Phase I patients must not be receiving greater than mg dexamethasone/day (or an equivalent amount of an alternative corticosteroid) for at least week prior to treatment start Has a diagnosis of immunodeficiency including human immunodeficiency virus (HIV) (HIV / antibodies) and is not on continuous daily immunosuppressive therapy within days prior to the first dose of trial treatment; (an exception to this is the use of steroids for brain edema and resulting symptom); subjects may receive a stable or reducing dose of steroids (up to mg dexamethasone or equivalent for at least days prior to signing consent) to prevent or manage cerebral edema; subjects requiring over mg of dexamethasone per day on or five days prior to signing consent are excluded) Received anti-myeloma treatment within weeks or pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone mg/day for a maximum of days before treatment Corticosteroids will be allowed at enrollment and during the first month of treatment with T-DM after SRS, up to a dose of no more than mg of dexamethasone daily or equivalent; patients that need to continue corticosteroids after the initial month will be allowed to continue in the protocol treatment if no further increase in dose is necessary; patients that need increase in dose of corticosteroid after initial month will be taken off protocol treatment Patients who are on dexamethasone receiving > mg/day in the two weeks prior to admission for intra-cerebral delivery of PVSRIPO Requires treatment with high dose systemic corticosteroids defined as dexamethasone > mg/day or bioequivalent for at least consecutive days within weeks of registration Dexamethasone dose should be =< mg/day or steroid equivalent prior to starting treatment; if higher doses are needed, consult with study chair Patients on greater than mg per day of dexamethasone within the weeks prior to admission for PVSRIPO infusion Ongoing or recent (within days prior to study entry) use of high dose oral corticosteroids (>= mg of dexamethasone daily or equivalent); intranasal and/or inhaled corticosteroid use is permitted High doses of systemic corticosteroids within days prior to first dosing; high dose is considered as > mg of dexamethasone a day (or equivalent) for > consecutive days Is taking > mg/day of dexamethasone or its equivalent at the start of immunotherapy or has required > mg/day of dexamethasone or its equivalent for consecutive days within week of starting treatment AT THE TIME OF INFUSION: Subjects should have been off other investigational antineoplastic therapy for two weeks prior to entry in this study; temozolomide will be allowed up to hours pre-infusion; dexamethasone up to a total dose of mg per day will be allowed if medically indicated Patients must be clinically stable and off or on low-dose (no more than . mg/kg/day, max mg/day dexamethasone) corticosteroid for at least one week prior to study registration Use of immunosuppressives within four weeks prior to study entry or anticipated use of immunosuppressive agents; dexamethasone, or other corticosteroid medications, if used in the peri-operative period must be tapered to no more than . mg/kg/day, max mg/day dexamethasone for at least one week before study registration; topical corticosteroids are acceptable Systemic corticosteroid therapy > mg of dexamethasone or equivalent per day at study entry Patients on greater than mg per day of dexamethasone within the weeks prior to admission for DC-IT infusion Research participant must not require more than mg three times daily (TID) of dexamethasone on the day of PBMC collection. Steroid use is allowed as long as dose has not increased within weeks of scheduled M administration; whenever possible, the patient should be on a steroid dose that is equivalent to a dexamethasone dose of =< mg daily at the time of treatment Required steroid increase within weeks of scheduled M administration; when possible, the patient should be on a dexamethasone equivalent dose of =< mg daily at the time of treatment Patients are allowed up to two cycles of high dose steroids (maximum total dose of mg dexamethasone or equivalent) if needed for symptomatic disease before study enrollment Patients currently receiving high dose systemic steroids for treatment of MM in excess of mg total dose of dexamethasone or equivalent, patients who received an investigational agent within half-lives of the agent Systemic corticosteroid therapy must be at a dose of =< mg of dexamethasone or equivalent per day during the week prior to day Patients must be clinically stable and off or on low-dose (no more than . mg/kg/day, max mg/day dexamethasone) corticosteroid for at least one week prior to study registration Use of immunosuppressives within four weeks prior to study entry or anticipated use of immunosuppressive agents; patients must be on no more than . mg/kg/day, max mg/day dexamethasone for at least one week before study registration; topical corticosteroids are acceptable Patients on total daily dose of dexamethasone greater than mg Patients needing more than mg dexamethasone per day at the time of start of WBRT will not be eligible to participate in the study; however, patients will be allowed entry into the study if it is medically safe to reduce the daily dose of dexamethasone to mg or less from the day of the start of WBRT; the dexamethasone dose for such patients may be increased beyond mg per day during the course of treatment if medically necessary; this increased need for dose should be communicated to the studys principal investigator, Dr Mohindra at the University of Maryland Patients must be clinically stable and off or on low-dose (no more than . mg/kg/day, max mg/day dexamethasone) corticosteroid for at least one week prior to study registration Use of immunosuppressives within four weeks prior to study entry or anticipated use of immunosuppressive agents; dexamethasone, or other corticosteroid medications, if used in the peri-operative period and/or during radiotherapy, must be tapered (no more than . mg/kg/day, max mg/day dexamethasone) for at least one week before study registration; topical corticosteroids are acceptable Medical need for the continuous administration of any drugs which affect CYPA though the use of low dose glucocorticoids (e.g. dexamethasone =< mg daily or equivalent) for anorexia and /or nausea is permitted Patients who are receiving high dose steroids (more than a dexamethasone-equivalent dose of mg per day). Dexamethasone at cumulative doses of greater than mg or equivalent < weeks prior to study Day is not allowed. Use of topical or inhaled steroids is acceptable Patients with active autoimmune diseases or active immune suppressive therapy or inflammatory bowel disease; a low dose steroid daily administration (equivalent dexamethasone < mg/day) is acceptable Systemic corticosteroid therapy is permitted provided dosing is no greater than mg per day (dexamethasone or equivalent) on the day of vaccine administration. Systemic corticosteroid therapy, > mg of dexamethasone daily (or equivalent) at study enrollment Concurrent Therapy \r\n* Patients who are receiving any other anticancer or investigational drug therapy\r\n* Patients requiring systemic treatment with either corticosteroids (greater than dexamethasone . mg/m^/day or the equivalent dose of other steroids) or other immunosuppressive medications within days of study drug administration will be excluded; however, patients who require intermittent use of bronchodilators or local steroid injections will not be excluded from the study Stable topical steroid therapy with dexamethasone, clobetasol, or budesonide oral solutions ( min, four times a day) for seven days prior to study enrollment Concurrent use of high dose steroids; chronic steroid use of < mg dexamethasone or equivalent per day is permissible A patient's daily total dose of dexamethasone must be =< mg by day Patients receiving chronic, systemic treatment with corticosteroids (of more than mg/day or equivalent of dexamethasone; doses of dexamethasone of up to mg/day may be administered for less than weeks) or another immunosuppressive agent; topical or inhaled corticosteroids are allowed Has not had prior systemic therapy for multiple myeloma. An emergency course of steroids (defined as no greater than milligram [mg] of dexamethasone, or equivalent per day for a maximum of days (that is, a total of mg) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles - of study treatment as needed for lytic bone disease Non-escalating corticosteroid dose (not exceeding more than mg daily of dexamethasone oral) for >= days Participant has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone mg/day for days) of corticosteroids before treatment Patients needing more than mg dexamethasone per day at the time of start of WBRT will not be eligible to participate in the study; however, patients will be allowed entry into the study if it is medically safe to reduce the daily dose of dexamethasone to mg or less from the day of the start of WBRT; the dexamethasone dose for such patients may be increased beyond mg per day during the course of treatment if medically necessary; this increased need for dose should be communicated to the studys principal investigator, Dr Mohindra at the University of Maryland No more than mg dexamethasone (or equivalent) per day Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid (ie, less than or equal to the equivalent of dexamethasone mg/day for days; such a short course of steroid treatment must not have been given within days of Cycle Day ), for Cohort C, the induction and consolidation treatment along with the first Autologous stem cell transplantation (ASCT) are allowed) Participants no longer need to be able to receive intravenous (IV) dexamethasone or an equivalent IV corticosteroid Systemic corticosteroid therapy is permitted provided dosing is no greater than mg per day (dexamethasone or equivalent) on the day of vaccine administration Immunosuppressants: patients must be receiving a stable or decreasing dose of dexamethasone for at least week prior to start of therapy AND dexamethasone dose must be =< . mg/kg/day AND =< a total daily dose of mg/day Stable dose of steroids for days, no more than mg dexamethasone (or equivalent) total per day Requires treatment with high dose systemic corticosteroids defined as dexamethasone > mg/day or bioequivalent for at least consecutive days within weeks of start of study drug Patient requires more than mg of dexamethasone daily or the equivalent Participant has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone mg/day for days) of corticosteroids before treatment Corticosteroid therapies of > mg/day prednisone, > mg/day dexamethasone, > mg/day hydrocortisone, or equivalent; oral, inhaled, or topical steroids are allowed during study as long as it does not exceed mg/day hydrocortisone Foreseeable condition which would preclude the reduction of steroids (dexamethasone) to a maximum of mg BID within a week prior to apheresis - Dexamethasone at cumulative doses greater than mg or equivalent within days prior to the first dose of study treatment is not allowed. Use of topical or inhaled steroids is acceptable. Patients on total daily dose of dexamethasone greater than mg/day Patients taking greater than mg daily of dexamethasone Patients on greater than mg per day of dexamethasone within the weeks prior to admission for PVSRIPO infusion Clinically stable and off or on low dose (no more than . mg/kg/day, maximum of mg/day dexamethasone) corticosteroid for at least week prior to study enrollment Systemic corticosteroids (e.g. prednisone >= . mg/day or dexamethasone >= mg/day) for the purpose of palliating tumor-related symptoms will not be allowed within week of starting treatment on trial High doses of systemic corticosteroids within days prior to first dosing. High dose is considered as > mg of dexamethasone a day (or equivalent) for > consecutive days Exclusion Criteria (Part B): Requirement of systemic corticosteroid therapy > mg/day of dexamethasone or equivalent or requirement of increasing dose of systemic corticosteroids during the days prior to the start of SL- treatment. Contraindication to any of the required concomitant drugs, including antiviral (e.g. Valacyclovir) and proton-pump inhibitor (e.g. lansoprazole). Corticosteroid therapy in a dose equivalent to dexamethasone ? . mg/day or prednisone ? mg/day. (Steroid use is allowed if necessary to treat spinal cord compression and/or hypocalcaemia.) Patients must be on a steroid dose less than or equal to mg of dexamethasone daily (or equivalent), and this dose must not have increased for at least days prior to obtaining the enrollment. Systemic corticosteroid therapy > mg of dexamethasone daily (or equivalent) at study enrollment. If a patient is on corticosteroids, he/she must be on a non-escalating corticosteroid dose (not exceeding more than mg daily of dexamethasone oral) for >= days taking more than mg of dexamethasone per day Corticosteroid therapy at a dose equivalent to dexamethasone > mg/day within days prior to randomization Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid [i.e., less than or equal to the equivalent of dexamethasone mg/day for days; such a short course of steroid treatment must not have been given within days of randomization]). Systemic corticosteroid therapy > mg of dexamethasone or equivalent (as defined by the investigator) per day at study enrollment. For patients on oral corticosteroids, they must be stable clinically on corticosteroids or tapered off prior to starting the study drug; for patients taking dexamethasone, the dose should not exceed mg QD (or mg twice daily [BID]), if clinically stable, and the dose should not be escalated over entry dose level, if clinically possible; the patients dose of dexamethasone will be evaluated by the principal investigator (PI), the patients study physician, and/or the study pharmacist on a case by case basis for safety; all doses of oral corticosteroids will be reduced by %, unless oral corticosteroids are at physiologic dose (e.g. dexamethasone mg, prednisone mg, or cortisone mg); it is recommended that oral corticosteroid doses be escalated back to full dose on day ( days after aprepitant is discontinued) Dexamethasone dose must be provided for treatment group assignment:\r\n* Group A: patients not on dexamethasone or on a dose =< . mg daily (or equivalent of an alternative corticosteroid)\r\n* Group B: patients who require dexamethasone >= mg daily (or equivalent of an alternative corticosteroid)\r\n** Patients must have been on the group assignment dose of corticosteroids for at least days prior to the dose of NT-I; corticosteroid dose changes prior to the start of treatment are allowed as long as they do not alter patients group assignment Patient requires more than mg of dexamethasone daily or the equivalent More than days of previous treatment (before screening) with anti-myeloma therapy (does not include radiotherapy or a single short course of steroid [ie, less than or equal to the equivalent of dexamethasone mg/day for days]).