The purpose of this study is to develop a novel platform for allo-SCT in multiple myeloma (MM) with the idea of maximizing anti-myeloma effect with conditioning and minimizing GvHD (graft versus host disease). Specifically, the investigators will use the Flu/Mel (fludarabine and melphalan) regimen. For GvHD prophylaxis, the investigators use the Hopkins PT-Cy (post-transplant cyclophosphamide) platform with the novelty of adding tocilizumab as both an anti-myeloma therapy and as a method to reduce GvHD. IL-6 has an important role in promoting the growth of myeloma cells and progression of disease.

Inclusion Criteria:

• Histologically confirmed diagnosis of myeloma.

• Between 18 and 70 years of age (inclusive).

• Karnofsky performance status ≥ 50% or ECOG performance score of ≤ 2 -Completion of last anti-myeloma therapy (if any) must occur at least 14 days before conditioning.

• Must have an HLA-matched sibling, HLA-matched unrelated donor, or a related haploidentical donor:

• Available HLA-matched sibling or unrelated donor must meet the following criteria:

  • At least 18 years of age
  • HLA donor/recipient match based on at least low-resolution typing per institutional standards (syngeneic donors [identical twins] are excluded)
  • In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting stem cells
  • No active hepatitis
  • Negative for HTLV and HIV
  • Not pregnant

OR

• Available haploidentical donor must meet the following criteria:

  • Blood-related family member (sibling (full or half), offspring, parent, cousin, niece or nephew, aunt or uncle, or grandparent)
  • At least 18 years of age
  • HLA-haploidentical donor/recipient match by at least low-resolution typing per institutional standards
  • In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting stem cells
  • No active hepatitis
  • Negative for HTLV and HIV
  • Not pregnant

• Normal bone marrow and organ function as defined below within 14 days prior to first study drug dose (conditioning regimen):

  • Total bilirubin ≤ 2.5 mg/dl
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN
  • Creatinine ≤ 2.0 x ULN OR estimated creatinine clearance ≥ 30 mL/min/1.73 m2 by Cockcroft-Gault Formula (See Appendix C)
  • Oxygen saturation ≥ 90% on room air
  • LVEF ≥ 40%
  • FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted

• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry through Day +100 visit. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

• Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis.
• Presence of another concurrent malignancy requiring treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan, cyclophosphamide, or other agents used in the study.
• Presence of an uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and/or breastfeeding.
• Previous treatment with tocilizumab (TCZ).
• Immunization with a live/attenuated vaccine within 28 days prior to conditioning.
• Any history of recent serious bacterial, viral, fungal, or other opportunistic infections, precluding a stem cell transplant according to the treating physician.
• Serologic evidence of HIV
• Active infection with Hepatitis A, B, or C. Active infection is defined as serologic positivity and elevated liver function tests.
• History of tuberculosis
• Active infection with EBV as defined as EBV viral load ≥ 10,000 copies per mL of whole blood; EBV viral load testing is only required if the patient has clinical signs or symptoms suggestive of active EBV infection
• Active infection with CMV as defined as CMV viral load ≥ 10,000 copies per mL of whole blood; CMV viral load testing is only required if the patient has clinical signs or symptoms suggestive of active CMV infection
• History of complicated diverticulitis, including fistulae, abscess formation or gastrointestinal (GI) perforation.
• Pre-existing CNS demyelination or seizure disorders
• Major surgery within preceding 8 weeks
• Body weight >150kg
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies.