Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma

Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma

Mixed chimerism transplantation is an approach to allogeneic transplants that attempts to decrease regimen-related toxicity by using non-myeloablative preparatory regimens; establish mixed chimerism using low dose total body irradiation along with immunosuppression using cyclosporine and mycophenolate mofetil; suppress graft-vs-host and host-vs-graft reactions to allow a mixed chimeric state to be established, encourage tolerance and prevent graft-vs-host disease (GvHD) during the mixed chimerism period and use donor lymphocyte infusions to convert the patient to a full chimera while developing a graft-vs-tumor effect.

Participants are mobilized with cyclophosphamide 4 g/m2 and filgrastim 10 µg/kg/day for peripheral blood progenitor cell (PBPC) collection by apheresis. Transplant conditioning is high-dose melphalan 200 mg/m2, followed by PBPC infusion as melphalan rescue [ie, autologous hematopoietic cells transplant (auto-HCT)]. Post-infusion support includes filgrastim 5 µg/kg/day, starting 6 days following melphalan. Participants with stable or responsive disease at 4 weeks eligible to continue on to the planned allogenic HCT (allo-HCT). For allo-HCT, a sibling donor that is fully matched for human leukocyte antigen (HLA-matched) is identified. Participants receive a single dose of total body irradiation (TBI) 200 centigray (cGy) as well as immunosuppression with cyclosporine (CSP) 6.25 mg/kg and mycophenolate mofetil (MMF) 15 mg/kg. The HLA-matched donor begins filgrastim injections 16 µg/kg/day on day -4 continuing to Day 0, with apheresis collections on Day -1 and Day 0, to a target of > 5 x 10e6 CD34 cells/kg. Allo-HCT is infused to participant on Day 0, with premedication hydrocortisone 100 mg IV and diphenhydramine 50 mg IV. CSP will be tapered beginning Day 56 with a goal of discontinuing CSP on Day 180, adjusted as needed.

PATIENT INCLUSION CRITERIA

• Multiple myeloma, early Stage II-III or relapsed / progression after initial treatment of Stage I disease
• Patient has HLA-identical sibling donor
• Age ≤ 70 years
• No prior therapy which would preclude the use of low-dose total body irradiation
• Pathology review and diagnosis confirmation by Stanford University Medical Center
• Karnofsky performance status (KPS) > 70%
• DLCO ≥ 60% predicted
• ALT and AST < 2 x upper limit of normal (ULN)
• Total bilirubin < 2 mg/dL
• Serum creatinine < 2.0, or 24-hour creatinine clearance ≥ 60 mL/min
• HIV-negative
• Signed informed consent document

PATIENT EXCLUSION CRITERIA

• Smoldering multiple myeloma; monoclonal gammopathy of unknown significance; or primary amyloidosis
• Severe psychological or medical illness
• Prior allogeneic hematopoietic cell transplantation
• Pregnant or lactating

ALLOGENEIC DONOR INCLUSION CRITERIA

• Age ≥ 17
• HIV-seronegative
• Signed informed consent document

ALLOGENEIC DONOR EXCLUSION CRITERIA

• Serious medical or psychological illness
• Pregnant or lactating
• Prior malignancies within the last 5 years, except for non-melanoma skin cancers