Lenalidomide with or without an Allogeneic Myeloma Vaccine and Prevnar-13 in Treating Patients with Newly Diagnosed, Recurrent, or Refractory Multiple Myeloma

Inclusion Criteria

• Myeloma eligibility criteria are the following: * Near complete remission (nCR) for >= 3 months defined as no measurable M-spike, and a positive serum immunofixation ** For patients with a light chain only myeloma, they will be in deemed to be in a complete remission (CR) if they meet criteria for CR by International Myeloma Working Group (IMWG) concensus criteria 2016 ** For patients with a light chain only myeloma that meet criteria for very good partial response (VGPR) by IMWG consensus criteria 2016 and are immunofixation electrophoresis (IFE) negative (–ve) (negative serum immunofixation), they will be considered to be in a near complete remission (nCR) * Or complete remission (CR) (no measurable M-spike, immunofixation negative and bone marrow plasma cells < 5%) * Newly diagnosed multiple myeloma (NDMM) or relapsed/refractory multiple myeloma (RMM) in nCR or CR having completed a minimum of 6 cycles of a lenalidomide based regimen for a minimum of >= 3 months * NDMM or RMM a patients who have been off corticosteroids for >= 4 weeks * Patients with NDMM or RMM who have had autologous stem cell transplant are eligible, but must be >= 12 months from transplant * All patients must be minimal residual disease (MRD) positive at 10^-4 or greater by next generation sequencing (NGS) sequencing at enrollment
• All patients must be currently taking Revlimid t screening
• Eastern Cooperative Oncology Group (ECOG) performance scores 0-2
• History of measurable serum or urine M protein or free light chains
• Life expectancy greater than 12 months
• Corrected serum calcium < 11 mg/dL, and no evidence of symptomatic hypercalcemia
• Serum creatinine < 2 mg/dl
• Absolute neutrophil count (ANC) > 1000/uL
• Platelet > 100,000/uL
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN
• Ability to comprehend and have signed the informed consent
• Have previously agreed to continue on maintenance therapy with lenalidomide concurrent with vaccine administration until disease progression, or clinical indication to cease therapy
• All patients must be willing and able to comply with the requirements of the Revlimid Risk Evaluation and Mitigation Strategies (REMS) program as directed by their providers
• All study participants will have been registered into the mandatory Revlimid REMS program as per standard of care, prior to enrollment
• Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to starting lenalidomide with each cycle (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy * A female of childbearing potential 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)
• Able to take prophylactic anticoagulation (aspirin 81 or 325 mg/daily or, for patients intolerant to acetylsalicylic acid [ASA], warfarin or low molecular weight heparin)

Exclusion Criteria

• Disease progression after stopping corticosteroids as defined as the appearance of a detectable serum or urine M-spike, or an absolute increase of > 10 mg/dl between involved and uninvolved light chains, in the absence of measurable serum or urine M-protein
• Patients who are MRD negative by NGS at screening
• Patients with a known diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, plasma cell leukemia, central nervous system (CNS) involvement, non-secretory myeloma and amyloidosis
• High-risk myeloma defined by presence of at least one of the following defining features on initial diagnostic, or most recent bone marrow biopsy: * High risk chromosomal translocations by fluorescence in situ hybridization (FISH): t(4;14), t(14;16), t(14;20) * del(17p), del(1p), amplification 1q * My prognostic risk score (PRS) gene expression profile (GEP)-70 or SkylineDx high risk signature either from diagnosis or at time of registration for the study * Lactate dehydrogenase (LDH) > 300 U/L at diagnosis * Relapse from prior therapy within 12 months
• Human immunodeficiency virus (HIV) disease, active infection requiring treatment with antibiotics, anti-fungal or anti-viral agents within 2 weeks of enrollment would be excluded from the study
• History of a pre-existing malignancy other than myeloma within the last 5 years with exception of treated basal cell or squamous cell carcinoma of the skin, or carcinoma “in situ” of the uterus, cervix or breast
• Patients who have participated in any clinical trial, within the last four weeks, which involved an investigational drug
• Autoimmune disease requiring active treatment
• Known contra-indication to any component of allogeneic myeloma vaccine
• History of an allogeneic transplant