With so many new therapies for myeloma it can be difficult to keep up. Professor Guy Pratt speaks to Helen about recent changes to diagnosis of myeloma and emerging therapies
Professor Guy Pratt
Key learning points
Diagnosis
In addition to symptomatic disease (CRAB) + plasma cells >10% + paraprotein, multiple myeloma can also be defined by presence of biomarkers:
- >=60% plasma cells
- >=1 lytic lesion on imaging
- SFLC ratio >= 100
Smouldering myeloma defined by features including 10-60% plasma cells, paraprotein >30g/L and SFLC ratio <100, no symptomatic bone disease and no end organ damage.
MGUS – pp <30g/L and <10% plasma cells in the bone marrow. IgA has a higher progression risk than IgG. Should also check albumin:creatinine ratio and proBNP to exclude amyloid.
BMAT and cross-sectional imaging for those at higher risk of progression.
Monoclonal gammopathy of renal significance, MGRS – rare, renal impairment and an elevated light chains– need renal biopsy.
Cross- sectional imaging – capacity and cost implications. Diffusion weighted MRI ideal. False positive with PET of 10%.
1st line treatment:
Fit- Bortezomib (Velcade) triplet (VTD or VCD, VRD in future)
Fit but renal impairment- VCD
Frail/older patient- VMP (fixed duration but SC injections of velcade) or lenalidomide + dexamethasone (continuous but oral)
Assess response after 4 th cycle of chemo. Aiming for VGPR at least.
Autograft following VGPR or CR 1 st line. If VGPR not reached, aim for deeper response e.g. with DT-PACE prior to autograft. Autograft increases PFS.
Lenalidomide maintenance post auto gives PFS of 2 years – not currently NICE approved.
Minimal residual disease D+100 post auto or post chemo- very prognostic. Useful in trials for surrogate marker treatment efficacy.
2nd line: re-induction with bortezomib, daratumumab and dexamethasone + 2nd autograft
3rd line: Ixazomib, lenalidomide, dexamethasone
4th line: dartatumumab single agent
Other subsequent lines: pomalidomide combinations, bortezomib and panobinostat
Other future agents: venetoclax, CAR-T, carfilzomib, PD-1 inihbitors
Supportive treatment:
TEAMM trial – showed benefit for levofloxacin daily for first 60 days of therapy and reduced hospital infection related admissions.
Bisphosphonate-myeloma IX survival benefit with zolendronic acid monthly. Side effects: osteonecrosis of the jaw and atypical fractures with long term duration.
Useful links
IMWG definitions
Myeloma IX bisphosphonate use
Imaging in multiple myeloma
Key learning points
Diagnosis
In addition to symptomatic disease (CRAB) + plasma cells >10% + paraprotein, multiple myeloma can also be defined by presence of biomarkers:
- >=60% plasma cells
- >1 lytic lesion on imaging
- SFLC ratio > 100
Smouldering myeloma defined by features including 10-60% plasma cells, paraprotein >30g/L and SFLC ratio <100, no symptomatic bone disease and no end organ damage,
MGUS – pp <30g/L and <10% plasma cells in the bone marrow. IgA has a higher progression risk than IgG. Should also check albumin:creatinine ratio and proBNP to exclude amyloid.
BMAT and cross-sectional imaging for those at higher risk of progression.
Monoclonal gammopathy of renal significance, MGRS – rare, renal impairment and an elevated light chains– need renal biopsy.
Cross- sectional imaging – capacity and cost implications. Diffusion weighted MRI ideal. False positive with PET of 10%.
1st line treatment:
Fit- Bortezomib (Velcade) triplet (VTD or VCD, VRD in future)
Fit but renal impairment- VCD
Frail/older patient- VMP (fixed duration but SC injections of velcade) or lenalidomide + dexamethasone (continuous but oral)
Assess response after 4 th cycle of chemo. Aiming for VGPR at least.
Autograft following VGPR or CR 1 st line. If VGPR not reached, aim for deeper response e.g. with DT-PACE prior to autograft.
PFS 2.5 years on average for 1st line autograft
Lenalidomide maintenance post auto gives PFS of 2 years – not currently NICE approved.
Minimal residual disease D+100 post auto or post chemo- very prognostic. Useful in trials for surrogate marker of effect of treatment but clinical value uncertain for influencing management.
2nd line: re-induction bortezomib, daratumumab and dexamethasone + 2nd autograft
3rd line: Ixazomib, lenalidomide, dexamethasone
4th line: dartatumumab single agent
Other subsequent lines: pomalidomide combinations, bortezomib and panobinostat
Other future agents: ventoclax, CAR-T, carfilzomib, PD-1 inihbitors
Supportive treatment:
TEAMM trial – showed benefit for levofloxacin daily for first 60 days of therapy and reduced hospital infection related admissions.
Bisphosphonate-myeloma IX survival benefit with zolendronic acid monthly. Side effects: osteonecrosis of the jaw and atypical fractures with long term duration.
Useful links
IMWG definitions
Myeloma IX bisphosphonate use
Imaging in multiple myeloma
