European Myeloma Network Consensus Statement on Functional High-Risk Multiple Myeloma
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Published on: September 13, 2016
Sueh-Li Lim1,2, Monika Engelhardt3, Evangelos Terpos4
1Australian Centre for Blood Diseases Monash University, Melbourne, Australia.
Abstract:
Multiple myeloma (MM) is an incurable blood cancer characterized by clonal bone marrow plasmacytosis, hypercalcemia, renal failure, anemia, and osteolytic bone disease. Approximately 20% of NDMM patients, not predicted to have high-risk disease at diagnosis, progress early, despite optimal induction +/- ASCT and lenalidomide maintenance, and are subsequently categorized as functional high-risk (FHR) disease. Standardized risk-stratification models incorporate biomarkers of tumor burden, existence of high-risk cytogenetics, with the presence/absence of plasma cell leukemia/extramedullary disease to attribute high-risk at diagnosis; however, depth/duration of response to novel agent-based induction (NA-IND) as dynamic markers of disease risk have not been defined. However, irrespective of diagnostic risk-stratification, response to NA-IND may be the single most effective method of identifying patients whose FHR biology portends an unacceptably short overall survival (OS). In this EMN consensus statement, we define FHR-MM as disease progression within 18 months of commencement of first-line therapy in the absence of high-risk cytogenetics, discuss the underlying disease biology, and strategies to improve outcomes for these patients.
Insights
Early progression in multiple myeloma (MM), termed functional high-risk (FHR) MM, despite initial treatment, indicates poor outcomes. Defining FHR-MM is crucial for identifying patients needing intensified therapy for better survival.
Area of Science:
- Hematology
- Oncology
- Internal Medicine
Background:
- Multiple myeloma (MM) is an incurable blood cancer with diverse clinical manifestations.
- A subset of newly diagnosed MM (NDMM) patients, initially classified as low-risk, experience early progression.
- This early progression, termed functional high-risk (FHR) MM, leads to significantly shorter overall survival.
Purpose of the Study:
- To define functional high-risk multiple myeloma (FHR-MM) based on early treatment response.
- To discuss the underlying biology of FHR-MM.
- To propose strategies for improving outcomes in FHR-MM patients.
Main Methods:
- This is an European Myeloma Network (EMN) consensus statement.
- The study defines FHR-MM as progression within 18 months of first-line therapy without high-risk cytogenetics.
- It reviews existing risk-stratification models and the role of novel agent induction response.
Main Results:
- Novel agent induction (NA-IND) response may be a more potent predictor of survival than initial diagnostic risk stratification.
- Early progression (within 18 months) in NDMM patients, irrespective of initial risk, identifies a group with poor prognosis.
- Functional high-risk (FHR) MM biology is distinct and requires further investigation.
Conclusions:
- Functional high-risk multiple myeloma (FHR-MM) is defined as early disease progression within 18 months of first-line therapy in the absence of high-risk cytogenetics.
- Response to novel agent induction (NA-IND) is a critical dynamic marker for identifying patients with poor prognosis.
- Further research into FHR-MM biology and development of improved therapeutic strategies are essential to enhance patient outcomes.
