Len/Dex/DLI in Relapsed Multiple Myeloma After Allogeneic Stem Cell Transplant

Myeloma patients in first relapse after sibling or unrelated donor allogeneic transplant willing to participate in this study will be screened for eligibility.

• After baseline evaluation including BM aspirate for plasma cell count, minimal residual disease using 8-color multiparameter flow cytometry, transcriptome sequencing and a positron emission tomography (PET scan), patients will receive Len- Dex daily x 21 days with Dex 40 mg once weekly for a total of 6 cycles of 28 days each
• Patients will then be evaluated clinically for acute and chronic GVHD before each cycle and a PET scan will be performed at the end of Len/Dex treatment
• Sibling and unrelated donor transplant recipients will receive 3 DLIs
• Disease and immune evaluation using serum and urine electrophoresis/immunofixation in addition to measurement of serum-free light chains, BM aspirate for plasma cell count and minimal residual disease using 8-color multiparameter flow cytometry, transcriptome sequencing and a PET scan will be performed

• A BM aspirate will be performed before each DLI for plasma cell count, MRD evaluation by flow cytometry and transcriptome sequencing
• Patients will be followed with a BM aspirate every 3 months x 1 year, then yearly and at progression for plasma cell count and evaluation
• Transcriptome sequencing will be done on BM aspirates at time of relapse, after Len/Dex cycles, 6m, 12m, 18m and 24m after the last-DLI.
• A PET scan will be performed after the last DLI and at progression.

Inclusion criteria

• Age 18-65 years
• Myeloma patients in first relapse after a sibling or unrelated allogeneic stem cell transplantation
• Patients with measurable disease at time of relapse based on the IMWG criteria
• All study participants must comply with the Revlimid Pregnancy Prevention Plan.
• Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid Pregnancy Prevention Plan.

Exclusion criteria

• Relapse occurred within 180 days post allograft
• Refractory to Len at any given time before allogeneic transplantation
• Presence of ≥ grade II or uncontrolled acute GVHD
• Presence of severe or uncontrolled chronic GVHD
• Karnofsky score < 70%
• Bilirubin > 50 μmol/L unless felt to be related to Gilbert's disease or hemolysis; AST and ALT > 5 x upper limit of normal (ULN); alkaline phosphatase > 5 x ULN
• Known hypersensitivity to Len or Dex
• Active infection with any of the following viruses: HIV, HTLV-1 or 2, hepatitis B (defined as HBsAg positivity) or hepatitis C (defined as anti-HCV positivity or HCV-RNA positivity)
• Presence of another malignancy with an expected survival estimated < 75% at 5 years (complete resection of basal cell carcinoma or squamous cell carcinoma, complete resection of a ductal carcinoma in situ, presence of lobular carcinoma in situ, complete resection of carcinoma in situ of the cervix, or an in situ or low-risk prostate cancer after curative therapy are not exclusion criteria)
• Positive beta-human chorionic gonadotropin pregnancy test, to be performed in all women of childbearing potential at screening and baseline. Female study participants who are surgically sterile (hysterectomy) or who have been postmenopausal for at least 12 consecutive months are automatically eligible for this criterion
• Females of child-bearing potential not agreeing to remain abstinent or to use 2 simultaneous effective methods of contraception from at least 4 weeks before, to at least 4 weeks following discontinuation of Len. Males not agreeing to use a condom during any sexual contact with females of child-bearing potential from at least 4 weeks before, to at least 4 weeks following discontinuation of Len
• Women who are lactating
• Female of child-bearing potential who are planning to become pregnant while enrolled in this study up to 4 weeks after the last Len dose
• Participation in a trial with an investigational agent within 30 days prior to entry in the study
• Inability to provide written informed consent prior to initiation of any study-related procedures, or inability, in the opinion of investigators, to comply with all requirements of the study
• Estimated probability to survive less than 6 months after initiation of Len and Dex
• Current history of drug and/or alcohol abuse
• Any abnormal condition or laboratory result that is considered by investigators capable of altering patient's condition, compliance or study outcome
• Any patient who, in the opinion of investigators, should not participate in this study
• Having received allogeneic stem cell transplantation in relapse after autologous transplant.
• Having received Len therapy after allogeneic transplant, before relapse
• Poor organ function defined as either: diffusing capacity of the lung for carbon monoxide corrected for hemoglobin using Dinakara method (DLCOc) < 50%; forced expiratory volume in 1 second < 50%; left ventricular ejection fraction (LVEF) < 40% evaluated by echocardiogram or multi-gated acquisition scan (MUGA); uncontrolled arrhythmia; symptomatic cardiac disease; creatinine clearance < 30 mL/minute; liver cirrhosis