Short summary

Smoldering multiple myeloma (MM) is an asymptomatic disorder with an annual risks of 10% of progression into the incurable cancer MM. While many patients live for many years without progression, high risk patients have a median risk of progression of 29 months. No therapy has been approved for this indication. New treatments with limited adverse events are in high demand for this unmet medical need. An effective peptide vaccine would represent an ideal candidate, since vaccines generally have very low levels of side effects.  This study will explore if vaccination against the immune checkpoint molecule PD-L1 leads to responses in patients with high risk MM that would potentially prevent or delay progression to symptomatic MM.

Rationale

Multiple myeloma (MM) is an incurable disease of malignantly transformed plasma cells with a 5-year survival of 43%. In most cases, MM is preceded by a premalignant asymptomatic stage, called smoldering MM (SMM). Due to the general perception that SMM do not cause any symptoms, the current standard care is to not actively treat patients, but rather continuously observe their disease state until symptomatic MM progression. Nevertheless, treatment options are desperately needed, as progression into an active disease state is associated with organ damage. An ideal treatment candidate is peptide vaccination, since vaccines may potentially prevent or delay progression of SMM into symptomatic myeloma. Nonetheless, any treatment needs to be non-toxic, not to affect the otherwise symptom-free stage of SMM, why an important part of this study will be to assess vaccine-related toxicities and adverse events throughout the treatment. Registration of adverse events is usually clinician-reported, but as some studies have shown that clinicians and patient-reported symptomatic toxicities do not highly correlate the patient-reported outcome assessment of common terminology criteria for adverse events (PRO-CTCAE) represents a valid instrument to illuminate the treatment-related toxicities in the current study. Further, since most patients may live years without progression, the protracted uncertainty of not knowing if, and when, their SMM diagnose turns into active disease state, this may impair the patients´ mental and physical health-related quality of life (HRQoL). However, little is known about the HRQoL of SMM patients, why collecting such data in the current trial is a unique opportunity to explore the extent of this aspect. 

The primary objective of this phase IIa trial is to investigate the rate of response in patients with high risk smoldering multiple myeloma vaccinated with the PD-1L long vaccination. Secondary objectives are to evaluate  immunogenicity of the vaccine, time to progression, overall survival besides clinician-rated and patient-reported safety and tolerability as well as health-related quality of life and anxiety using patient-reported outcomes.

Description of the cohort

20 patients (Age ?18 years) with high risk smoldering multiple myeloma (diagnosed < 5 years prior to inclusion) and a performance status ? 2 on the ECOG-scale.

Data and biological material

Primary endpoint: Overall response rate

Secondary and exploratory endpoints:

Progression-free survival, time to progression, overall survival, immunogenicity of the vaccine (blood and bone marrow), incidence of clinician-rated treatment emergent adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) besides patient-reported outcomes (PRO) on health-related quality of life (QLQ-C30) and anxiety (GAD-7) and patient-reported adverse events (PRO-CTCAE).

Collaborating researchers and departments

Center for Cancer Immune Therapy, Department of Hematology, Herlev and Gentofte University Hospital

• Head of Department Lene Meldgaard Knudsen, DMSc
• PhD-fellow Nicolai Grønne Dahlager Jørgensen, MD