Pembrolizumab as Salvage Therapy for the Treatment of Multiple Myeloma in Patients Progressing on CAR-T Cell Therapy

Subject is, in the investigator's opinion, willing and able to comply with the protocol requirements

Subject has given voluntary signed written informed consent before performance of any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care

Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1

Have documented multiple myeloma as defined by the International Myeloma Working Group (IMWG) 2014 criteria including: Clonal bone marrow plasma cells \>= 10% (If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement). In addition, the patient must meet one of the criteria in c1 or c2:

* Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically (one or more of the following):

* Hypercalcemia: serum calcium \> 0.25 mmol/L (\> 1 mg/dL) higher than the upper limit of normal (ULN) or \> 2.75 mmol/L (\> 11 mg/dL)

* Renal insufficiency: Creatinine clearance (CrCl) \< 40 mL/min (measured or estimated by validated equations) or serum creatinine \> 177 umol/L (\> 2 mg/dL)

* Anemia: hemoglobin value of \> 20 g/L below the lower limit of normal, or a hemoglobin value \< 100 g/L

* Bone lesions: 1 or more osteolytic lesions on skeletal radiography, computed tomography (CT), or magnetic resonance imaging (MRI) (Clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used)

* Any one or more of the following:

* Clonal bone marrow plasma cell percentage \>= 60% (Clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used)

* Involved: uninvolved serum free light chain (FLC) ratio \> 100 (These values are based on the serum Freelite assay. The involved FLC must be \>= 100 mg/L

* \> 1 focal lesions on MRI studies; Each focal lesion must be 5 mm or more in size

Measurable disease as defined by any of the following:

* Serum M-protein level \>= 1.0 g/dL or urine M-protein level \>= 200 mg/24 hours

* IgA, IgD, IgE, or IgM multiple myeloma: serum M-protein level \>= 0.5 g/dL or urine M-protein level \>= 200 mg/24 hours; or

* Light chain multiple myeloma without measurable disease in the urine: serum Ig free light chain (FLC) \>= 10 mg/dL and abnormal serum Ig kappa/lambda FLC ratio

Must have undergone BCMA-directed CART cell therapy and have evidence of progression per IMWG criteria upon response assessment

Must have at least 4-week washout period for all the investigational monoclonal antibodies

Men and women, age \>= 18 years or legal age of consent per local regulations (whichever is greater)

Female patients who:

* Are postmenopausal for at least 1 year before the screening visit, OR

* Are surgically sterile, OR

* If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR

* Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)

* Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting study drugs

Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:

* Agree to practice effective barrier contraception during the entire study treatment period and through 4 weeks after the last dose of study drug, OR

* Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)

Pembrolizumab as Salvage Therapy for the Treatment of Multiple Myeloma in Patients Progressing on CAR-T Cell Therapy

What this study is about

Pembrolizumab as Salvage Therapy for the Treatment of Multiple Myeloma in Patients Progressing on CAR-T Cell Therapy

What this study is about