Combination Treatment Therapy Approaches for the Treatment of High-Risk Multiple Myeloma, REACH Trial

Eligibility Criteria

• * PRE-REGISTRATION-
• * PRE-REGISTRATION EXCLUSION:
• * Monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, light chain amyloidosis with organ involvement.
• * Diagnosed or treated for another malignancy =\< 1 year prior to pre- registration or previously diagnosed with another malignancy and have any evidence of residual disease.
• * NOTE: Subjects with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• * Other co-morbidity which would interfere with subject's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease.
• * Other concurrent chemotherapy, or any ancillary therapy considered investigational. NOTE: Concurrent chemotherapy is any treatment not related to multiple myeloma.
• * NOTE: Concurrent chemotherapy is any treatment not related to multiple myeloma
• * NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment.
• * Peripheral neuropathy \>= grade 3 on clinical examination or grade 2 with pain =\< 30 days prior to registration.
• * Major surgery =\< 14 days prior to pre-registration.
• * Evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
• * Note: Prior to trial entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant.
• * New York Heart Association (NYHA) II, III, IV heart failure.
• * Known human immunodeficiency virus (HIV) positive.
• * Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (ie., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded.
• * EXCEPTION: subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• * Known or suspected active hepatitis C infection.
• * Any medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• * Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or investigator's brochure) or known sensitivity to mammalian-derived products. Known allergies, hypersensitivity, or intolerance to trial drugs.
• * Inability to comply with protocol/procedures.
• * REGISTRATION-