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:

Cardiac: LVEF at rest must be ≥ 50%

Hepatic:

< 3x ULN ALT
< 1.5 ULN total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
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
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:.

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.
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)