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 of prior therapy with at least a very good partial remission to most recent salvage therapy.

  * Patients should have R-ISS stage II or III disease at diagnosis or high risk cytogenetics 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 two progressions

* 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 benign hyperbilirubinemia.
  3. Renal: serum creatinine \<1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl \> 40 ml/min (measured or calculated/estimated) with dose adjustment 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 International Myeloma 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 with either corticosteroids (\>10 mg daily of prednisone equivalents) or other immunosuppressive medications at enrollment. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the 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) therapy will be considered eligible; patients with CMV viremia by PCR or disease with end-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 other immunomodulators
  * steroid dosing exceeding 10 mg/d prednisone or equivalent
* Receiving immunomodulatory agents (ex. thalidomide, lenalidomide, pomalidomide)