Topline Presentation Points
MM Is Not One Disease
- MGUS to Active MM transition period is different among patients. Diagnosis is made at variable time-points during the transition, so degree of end organ damage is different.
- Management strategies are focusing on changing myeloma to a chronic illness for majority of patients, probably curative for a subset. High risk disease remains a challenge.
- Advances in understanding myeloma biology has led to new therapeutic targets.
- MM Pathways
- BM microenvironment
- Immune regulation and modulation
(Martinez-Lopez J et al Blood 2011)
(Usmani et al Leukemia 2012)
Defining High Risk Disease at Diagnosis in 2021
- Clinical Phenotypes
- EMD (Extramedullary multiple myeloma) and pPCL (primary Plasma Cell Leukemia)
- MM Biology
- Cytogenetics/FISH
- Translocation (14;16) – MAF over-expression
- Translocation (14;20) – MAFB over expression
- Gain & Amplification of chromosome 1q21 – over expression of several proteasome genes
- Deletion 17 p – monoallelic loss is bad, biallelic loss is worse.
- Translocation (4;14)
- Poor Risk by Gene Expression Profiling
- Gene mutations
- BRAF, K-RAS, N-RAS (low incidence at diagnosis, usually late events)
- Blind Spots – that can lead to ‘unexpected’ poor responders or unexpected ‘early relapse’
- Poor assessment of MM disease biology at diagnosis and relapse:
- Highly dependent on the quality of random pelvic bone biopsy
- Can fix by creating standard operating procedure/process steps for sample ‘pecking order’.
- No assessment of FDG avid focal bone lesions or EMD
- Can fix by concomitant biopsy of such lesions as ‘routine’ practice. However, not patient friendly.
- [Patient] Only examined at finite time points
- Highly dependent on the quality of random pelvic bone biopsy
- Poor assessment of MM disease biology at diagnosis and relapse:
We are still learning how to incorporate immunome and BM microenvironment status in MM patient assessment.
We are still optimizing how best to assess depth of response/detect MRD status.
