This will be a 2 year study to evaluate and improve cancer sequencing as applied to the characterization of tumor molecular make-up and the identification of novel therapeutics (total n=100; approximately 50/year). Participants who will undergo tumor biopsy for management of multiple myeloma (MM) will self-refer to the study or be referred by their treating physician. Participants will initially meet with a clinician to review study consents and provide medical, medication, and family history information. After informed consent, biospecimen samples from peripheral blood, cheek swab, and tumor samples from bone marrow (aspirate and biopsy), peripheral blood, or any mass/fluid containing tumor cells will be obtained (from procedures indicated as part of their standard oncology care) for cancer sequencing (CS) (whole exome sequencing of germline and tumor genomes, RNA sequencing of tumor transcriptome, single cell, and CyTOF analysis). CS data will be interpreted via somatic variation identification, network modeling, and cancer transcriptome profiling to facilitate mapping activity levels of genes to networks and for identifying genes activated or dysregulated in cancer cells. Technologies and methodologies are developing rapidly, varying on a near daily basis which pre-empts our ability to define analysis and interpretation techniques in detail. Sequencing and analysis will be performed at the Genomics Core Facility at the Icahn School of Medicine at Mount Sinai. In instances where internal sequencing capabilities do not allow for certain types of analysis (e.g., a technology that is not yet available at Mount Sinai), de-identified samples or data may be sent out to third parties for additional analysis.. All external genetic tests will be performed in a CLIA certified lab and all tests will be FDA or NYS approved. The RNA Sequencing test will receive NYS Department of Health (Wadsworth Center) approval before results are provided to physicians . Samples will be de-identified and processed by the Mount Sinai Human Immune Monitoring Core (HIMC) before being sent to an external CLIA-certified lab for sequencing and analysis. Interpretation will be performed by a multidisciplinary team that includes genomicists, pathologists, and clinicians familiar with the particular cancer diagnosed in the participant. Once results are available, they will be shared with the study team. This study is not intended to implement the findings on CS, only to report the results obtained to the study team.

Inclusion Criteria:

• Patients must be 18 years of age at the time of registration.
• Participant must have an established diagnosis of relapsed Multiple Myeloma based on IMWG criteria, be willing to participate, and able to consent
• Participant must have a treating physician who agrees to participate in the study
• Participant will be undergoing a bone marrow biopsy or tumor biopsy as part of their standard of care.
• Patients must be willing to participate in this study and able to sign informed consent.
• Participants are not participating in any interventional clinical trial using systemic therapy directed towards control of MM.

Exclusion Criteria

• Known diagnosis of AL amyloidosis, Waldenstrom Macroglobulinemia, POEMS, or Castleman´s disease.
• Diagnosis of cancer other than myeloma or skin cancer (squamous cell or basal cell) that is ongoing or treated within the last 2 years.
• Tumor sample inadequate or unavailable for analysis (e.g., due to insufficient number of tumor cells).
• Patient will not be receiving systemic MM-directed chemotherapy/immunotherapy in the following 2 months from the time tumor biopsy is performed.

This study is open to interested patients with Multiple Myeloma (MM) of all genders and races from inside or outside Mount Sinai that will be undergoing tumor sampling (bone marrow or tissue) as part of their evaluation for salvage therapy. The research team will accept participants with a diagnosis of MM who self-refer, or are referred by their treating physician, who will be undergoing tumor biopsy (bone marrow or tissue) with the intention of receiving salvage systemic therapy for their MM. Interested individuals can contact the research team and learn more about the study. Potential participants would speak to one of the study staff over the phone, will be provided with further details about the study, pre-screened for eligibility, and set up to undergo informed consent.

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Beginning 9 months and ending 36 months following article publication.

Researchers who provide a methodologically sound proposal. To achieve aims in the approved proposal. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in the University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at (Link to be determined).