Vaccination With PD-L1 Peptide Against Multiple Myeloma

Background: Multiple myeloma is the second most common hematologic cancer which is despite advances in treatment is still incurable for most patients.

In this trial the investigators assess a new immunotherapeutic strategy targeting the immune checkpoint molecule PD-L1 to investigate the potential of vaccination against PD-L1 as a possible anticancer target.

PD-L1 has been recognized as an important factor in immune regulation and development of immune tolerance in the microenvironment of cancer cells. Cells that express PD-L1 on their surface are known to inhibit the immune system. As seen with the recent advances in immunotherapy against cancer with antibodies against PD-L1, the the immunosuppressive role of the molecule PD-L1 can be antagonized to the benefit of patients with cancer. PD-L1 is expressed on both cancer cells, antigen presenting cells and immunosuppressive cells in the tumor micro-environment. Vaccination against PD-L1 is therefore two sided. The investigators aim to stimulate PD-L1 specific T-cells, hence eliminating both PD-L1 positive tumor cells as well as PD-L1 positive immunosuppressive and antigen presenting cells in the tumor microenvironment. The primary endpoints are safety and toxicity evaluation. Secondary endpoint is immunological response. Clinical response will be described.

Inclusion criteria

• Histologically verified multiple myeloma
• Newly treated with HDT and no signs of relapse
• Age ≥18 years
• Performance status ≤ 2 (ECOG-scale)
• Expected survival > 3 months
• Sufficiently regenerated bone marrow function, i.e.

• Leucocytes ≥ 1,5 x 109
• Granulocytes ≥ 1,0 x 109
• Thrombocytes ≥ 20 x 109
• Creatinine < 2.5 upper normal limit, i.e. < 300 μmol/l
• Sufficient liver function, i.e.

• ALAT < 2.5 upper normal limit, i.e. ALAT <112 U/l
• Bilirubin < 30 U/l
• Women agreement to use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 120 days after the last treatment.
• For men: agreement to use contraceptive measures and agreement to refrain from donating sperm.

Exclusion criteria

• Non-secretory myeloma
• Other malignancies in the medical history excluding squamous cell carcinoma of the skin and patients cured for another malignant disease with no sign of relapse three years after ended treatment.
• Significant medical condition per investigators judgement e.g. severe Asthma/COPD, poorly regulated heart condition, insulin dependent diabetes mellitus.
• Acute or chronic viral infection e.g. HIV, hepatitis or tuberculosis
• Serious known allergies or earlier anaphylactic reactions.
• Known sensibility towards Montanide ISA-51
• Any active autoimmune diseases e.g. autoimmune neutropenia, thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, autoimmune glomerulonephritis, autoimmune adrenal deficiency, autoimmune thyroiditis etc.
• Pregnant and breastfeeding women.
• Fertile women not using secure contraception with a failure rate less than < 1%
• Patients taking immune suppressive medications incl. corticosteroids and methotrexate at the time of enrollment
• Psychiatric disorders that per investigator judgment could influence compliance.
• Treatment with other experimental drugs
• Treatment with other anti-cancer drugs - except bisphosphonates and denosumab
• Patients with active uncontrolled hypercalcemia
• Patients who have received chemotherapy, immune therapy, radiation therapy within the last 28 days.