Melphalan on Disease Burden Measured by Next Generation Sequencing Before AHCT (Autologous Hematopoietic Cell Transplant) for Multiple Myeloma

Inclusion Criteria:

* Participants must have diagnosis of symptomatic MM
* Participants must have received at least three cycles of anti-myeloma regimen including a proteasome inhibitor (i.e., bortezomib, carfilzomib or ixazomib) plus Lenalidomide or daratumumab, and have future plan of autologous stem cell transplant.
* Participants must have achieved Partial Response based on International Myeloma Working Group response criteria (Appendix II).
* Participants must have at least equal or greater than 100 mg/dL or 0.1 gr/dL monoclonal protein on serum electrophoresis and immunofixation at diagnosis
* Minimum 3 x10\^6/kg collected CD34+cells in one or multiple days. (CD=cluster of differentiation)
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Life expectancy ≥ 12 months
* Adequate hepatic function, as defined by:

  * Serum ALT ≤ 3.5 times the upper limit of normal (ALT=alanine aminotransferase)
  * Serum direct bilirubin ≤ 2 mg/dL (34 μmol/L) within 21 days prior to initiation of therapy
* Creatinine clearance (CrCl) ≥ 40 mL/minute within 21 days prior to start of therapy either measured or calculated using a standard formula (e.g., Cockcroft and Gault).
* Adequate bone marrow function ,as defined by:

  * Hemoglobin ≥ 10.0 g/dl
  * WBC (white blood cell count) ≥ 3.00 x 10\^9/L
  * Absolute neutrophil count ≥1.5 x10\^9/L
  * Platelets ≥ 100 x 10\^9/L ---Growth factors are not allowed to be used in order to meet adequate bone marrow function
* Written informed consent in accordance with federal, local, and institutional guidelines
* Participants of childbearing potential must agree to practice reliable contraception for at least 28 days before and for 60 days after last dose of study drug. Reliable contraception is defined as:

  * One highly effective method and one additional effective (barrier) method:

    * Examples of highly effective methods:

      * Intrauterine device (IUD)▪Hormonal (injections, implants, levonorgestrel releasing intrauterine system \[IUS\], medroxyprogesterone acetate depot injections, ovulation inhibitory progesterone-only pills \[e.g.desogestrel\])
      * Tubal ligation
      * Partner's vasectomy
    * Examples of additional effective methods

      * Male condom
      * Diaphragm
      * Cervical Cap

Exclusion Criteria:

* Prior treatment toxicities have not resolved to ≤ Grade 2 according to NCI CTCAE Version 5.0 (except neuropathy).
* Participant receiving any other investigational agents within 21 days prior to study/treatment
* Treatment with any anti-myeloma chemotherapy within 14 days
* Diagnosis of amyloidosis, POEMS.
* Major surgery, radiotherapy or infection requiring therapy within 14 days of starting study treatment.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan
* Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant or breastfeeding women are excluded from this study because melphalan is an alkalizing agent with the potential for teratogenic or abortifacient effects. Because there is unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with melphalan, breastfeeding should be discontinued if the mother is treated with melphalan
* Unstable angina or myocardial infarction within 4 months prior to registration, NYHA (New York Heart Association) Class II, III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker.
* Cerebrovascular disease manifested as prior stroke at any time or TIA (transient ischemic attack) in the 12 months prior to initiation of therapy
* Non-hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b)carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas.
* Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.