Study of Ipilimumab After Stem Cell Transplantation in People With Relapsed/Refractory Multiple Myeloma

Inclusion Criteria: Inclusion Criteria prior to Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT):

• Willing and able to participate as a research subject and provide informed consent (Note: an LAR may sign the consent form on the partipant's behalf)
• Diagnosis of relapsed refractory multiple myeloma defined as more than 2 lines ofprior therapy with at least a very good partial remission to most recent salvagetherapy.
• Patients should have R-ISS stage II or III disease at diagnosis or high riskcytogenetics by IMWG criteria (t(4;14), del(17/17p), t(14;16), t(14;20),nonhyperdiploidy, and gain(1q)) at any time since diagnosis Note:. A line of therapy is treatment between diagnosis and progression or between twoprogressions
• Eligible for CD34-selected HSCT according to MSKCC adult BMT guidelines.
• Have a 10/10 matched donor
• Age ≥ 21, < 73 years.
• Karnofsky (adult) Performance Status ≥ 70%.
• Patients must have adequate organ function measured by:

1. Cardiac: LVEF at rest must be ≥ 50%
2. Hepatic:

• < 3x ULN ALT
• < 1.5 ULN total serum bilirubin, unless there is congenital benignhyperbilirubinemia.

3. Renal: serum creatinine <1.2 mg/dl or if serum creatinine is outside the normalrange, then CrCl > 40 ml/min (measured or calculated/estimated) with doseadjustment of Fludarabine for <70ml/min
4. Pulmonary: DLCO > 50% of predicted (corrected for hemoglobin). Inclusion Criteria prior to Ipilimumab:

• Non progressive myeloma (partial response or better) as defined by InternationalMyeloma Working Group (IMWG) criteria
• Engraftment of all cell lines without transfusion dependence, defined as:
• absolute neutrophil count > 1.0K/mcL x 3 consecutive days
• platelets > 50K/mcLx 7 consecutive days without platelet transfusion
• no platelet or RBC transfusions within the preceding 7 days
• ≥ 80% donor chimerism in the bone marrow

Exclusion Criteria: Exclusion Criteria prior to Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT):

• Patients ineligible for therapy with ipilimumab, for example:.

1. Active autoimmune disease or any condition requiring systemic treatment witheither corticosteroids (>10 mg daily of prednisone equivalents) or otherimmunosuppressive medications at enrollment. Inhaled or topical steroids andadrenal replacement doses > 10 mg daily prednisone equivalents are permitted inthe absence of active autoimmune disease.
2. History of motor neuropathy considered to be of autoimmune origin (e.g.,Guillain-Barre Syndrome, Myasthenia Gravis).

• Female patients who are pregnant or breast-feeding.
• Patients with plasma cell leukemia at the time of diagnosis.
• Patients who have undergone prior allogeneic hematopoietic stem cell transplantation.
• Patients who have had a previous malignancy that is not in remission. Exclusion Criteria prior to Ipilimumab:
• Active infection or treatment for infection (patients on Cytomegalovirus (CMV) therapywill be considered eligible; patients with CMV viremia by PCR or disease withend-organ involvement will not be eligible)
• Active GVHD of any grade or prior grade 3-4 GVHD
• Active immune suppression, defined as:
• active use of calcineurin inhibitors, mycophenolate mofetil, or otherimmunomodulators
• steroid dosing exceeding 10 mg/d prednisone or equivalent
• Receiving immunomodulatory agents (ex. thalidomide, lenalidomide, pomalidomide)