| Eligibility |
Inclusion Criteria:
1. Must be able to understand and voluntarily sign an informed consent form (ICF).
2. Must be = 18 years of age at the time of signing the ICF.
3. Newly diagnosed multiple myeloma (according to the IMWG diagnostic criteria) receiving
standard of care CyBorD treatment and have not achieved at least VGPR or progressed
after 2 cycles of treatment.
4. Must have measurable disease according to the IMWG criteria as defined below:
1. Serum M-protein = 5 g/l
2. Urine M-protein = 200 mg/24 h
3. Serum free light chains (FLC) assay: Involved FLC level = 100 mg/l and an
abnormal serum free light chain ratio (< 0.26 or > 1.65)
5. Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1,
or 2.
6. Must not be eligible for consolidation with high dose chemotherapy and autologous stem
cell transplantation (ASCT).
7. Must not have any known congenital or acquired immune suppression.
8. Must have negative serology for HIV, HBV and HCV.
9. Male subject must agree to use contraception as detailed in Appendix 3 of this
protocol during the treatment period and for at least 120 days after the last dose of
study treatment and refrain from donating sperm during this period.
10. Female subject is eligible to participate if she is not pregnant (see Appendix 3 of
protocol), not breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 of
protocol OR
2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 of protocol
during the treatment period and for at least 30 days after the last dose of study
treatment.
11. Must have adequate organ function as defined below. Specimens must be collected within
10 days prior to the start of study treatment.
- Absolute neutrophil count (ANC) =1500/µL
- Platelets =100 000/µL
- Hemoglobin =9.0 g/dL or =5.6 mmol/La
- Creatinine OR Measured or calculated creatinine clearance (GFR can also be used
in place of creatinine or CrCl) =1.5 × ULN OR
=30 mL/min for subject with creatinine levels >1.5 × institutional ULN
- Total bilirubin =1.5 ×ULN OR direct bilirubin =ULN for subjects with total
bilirubin levels >1.5 × ULN
- AST (SGOT) and ALT (SGPT) =2.5 × ULN (=5 × ULN for subjects with liver
metastases)
- International normalized ratio (INR) OR prothrombin time (PT) Activated partial
thromboplastin time (aPTT) =1.5 × ULN unless subject is receiving anticoagulant
therapy as long as PT or aPTT is within therapeutic range of intended use of
anticoagulants
Exclusion Criteria:
1. Prior exposure to Pembrolizumab (or other anti-PD-1, anti-PD-L1, or anti-PD-L2 agent;
or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
(e.g., CTLA-4, OX 40, CD137)).
2. Known allergies, hypersensitivity to mannitol, corticosteroids, monoclonal antibodies
or human proteins, or their excipients (refer to the Pembrolizumab IB), or known
sensitivity to mammalian-derived products
3. History of prior allogeneic stem cell transplantation or solid organ transplantation
that requires immunosuppressive therapy.
4. History of prior autologous peripheral stem cell transplantation or bone marrow
transplantation for any indication.
5. Subject who is currently participating in or has participated in a study of an
investigational agent or has used an investigational device within 4 weeks prior to
the first dose of study treatment. Subjects who have entered the follow-up phase of an
investigational study may participate as long as it has been 4 weeks after the last
dose of the previous investigational agent.
6. Myeloma with known CNS involvement, plasma cell leukemia or amyloidosis.
7. Chemotherapy or other anti-myeloma therapy other than three or less cycles of CyBorD.
Prior bisphosphonates or other bone consolidation therapy is acceptable either if it
was given for myeloma or for any other indication.
8. Known congenital or acquired immune deficiency or ongoing chronic systemic steroid
therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form
of immune suppressive therapy within 7 days prior to the first dose of study drug for
any indication, excluding Dexamethasone or steroids given as part of myeloma
treatment.
9. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
10. Known chronic obstructive pulmonary disease (COPD), defined as a FEV1 <50% predicted
value.
11. Known moderate or severe persistent asthma within the last 2 years, or currently has
uncontrolled asthma of any classification.
12. History of or current uncontrolled cardiovascular disease including:
1. Unstable angina, myocardial infarction, or known congestive heart failure Class
III/IV (Appendix 5 of protocol) within the preceding 12 months.
2. Transient ischemic attack within the preceding 3 months, pulmonary embolism
within the preceding 2 months.
3. Any of the following: sustained ventricular tachycardia, ventricular
fibrillation, Torsades de Pointes, cardiac arrest, Mobitz II second degree heart
block or third-degree heart block; known presence of dilated, hypertrophic, or
restrictive cardiomyopathy.
4. QTc prolongation as confirmed by ECG assessment at screening (QTc >470
milliseconds).
13. Has an active infection requiring systemic therapy.
14. Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
15. Has received prior radiotherapy within 2 weeks of start of study treatment. Subjects
must have recovered from all radiation-related toxicities
16. Prior history of malignancies, other than MM, unless the subject has been free of the
disease for 3 years or longer. Exceptions include the following:
1. Basal or squamous cell carcinoma of the skin.
2. Carcinoma in situ of the cervix or breast
3. Adenocarcinoma of the prostate (TNM stage of T1a or T1b)
17. Women who are pregnant, breastfeeding or planning to become pregnant while enrolled in
this study, or within 90 days after the last dose of study medications. Male subject
who plans to father a child while enrolled in this study, or within 120 days after the
last dose of study medications.
18. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the study.
19. Has a history or current evidence of any condition (i.e. uncontrolled diabetes, active
or uncontrolled infection, acute diffuse pulmonary disease, pericardial disease,
uncontrolled thyroid dysfunction), therapy or laboratory abnormality that might
confound the results of the study, interfere with the subject's participation for the
full duration of the study, or is not in the best interest of the subject to
participate, in the opinion of the treating Investigator.
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