OVERVIEW. Background. The challenge of renal impairment in myeloma patients.MERIT.Design HistoryResults so farImplications. What is the extent of the problem? . Renal impairment occurs in 25- 30% of patients at presentation (Knudsen 1994, Kyle RA, 1975, Eleutherakis-Papaiakovou V et al, 20
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1. Management of renal failure in Myeloma patients.
Dr Judith Behrens
St Helier Hospital
2. OVERVIEW Background.
The challenge of renal impairment in myeloma patients.
Results so far
3. What is the extent of the problem? Renal impairment occurs in
25- 30% of patients at presentation
(Knudsen 1994, Kyle RA, 1975, Eleutherakis-Papaiakovou V et al, 2007).
50% of patients at some stage of the illness
(Alexanian, Barlogie and Dixon, 1990).
3-12% patients require dialysis or other major intervention
(Clark, Shetty and Soutar, 1999).
4. Why do patients with myeloma get renal damage? Light chain toxicity
Nephrotic drugs – particularly NSAIDS
Plasma cell infiltration
5. Importance of SFLC in IIMM
FLCs are abnormal in 95% at disease presentation.
concentrations are >1,000mg/L in 10- 15% of IgG and IgA cases with IIMM
characteristic of IgD multiple myeloma
6. Urinary flc excretion and renal failure by paraprotein class
IgG, 1367 patients; IgA, 649 patients; LCO, 310 patients.
Urinary flc excretion, Patients with renal failure no (%)
g/g creatinine IgG IgA LCO
0 g/g 28 (2) 29 (3) 0 (0)
Less than 4 g/g 48 (8) 46 (11) 22 (18)
4-12 g/g 13 (29) 12 (28) 18 (38)
More than 12 g/g 11 (48) 13 (48) 60 (54)
Blood 2006; 108: 2013 – 19
Effects of paraprotein heavy and light chain types and free light chain load on survival in myeloma:
Mark Drayson, Gulnaz Begum, Supratik Basu, Sudhaker Makkuni, Janet Dunn, Nicola Barth, and J. Anthony Child
7. Importance of SFLC in LCMM LCMM can be missed by conventional techniques.
SPE demonstrates a monoclonal band in 50% cases,
IFE demonstrates monoclonal bands in most cases but may be misinterpreted
Urine needed for identification and quantitation but urine tests may never arrive in the lab.
Serum Freelite assay pos 100% cases.
8. What is the effect of renal failure on outcome? 1973 MRC IV th trial median survival
urea> 13mmol/l= 2 months
urea < 6.5= 37 months
1995 median survival with renal impairment
(Torra, Blade et al BJH 1995)
20 -24 months
9. Impact of renal impairment on survival in myeloma patients 30% patients die in the first 60 -100 days (c.f. 10 % overall)
However those surviving the first 60 days have similar overall survival to patients without renal failure.
Normally IgG and IgA myeloma patients have longer survival than LCOM but in patients having the same quantity of BJP survival is the same for all isotypes
The degree of renal impairment predicts survival
Drayson et al. Analysis of MRC patients in 1Vth Vth V1th and V111th UK MRC trials
Blood June 2006
Thus rescuing the kidney is key
10. What is the likelihood of renal recovery? Until last decade widely quoted to be 10 % once dialysis dependent
11. Renal out come of Patients admitted to SW Thames Renal Unit 2000 -2007
12. Renal out come of Patients admitted to SW Thames Renal Unit 2000 -2007 Of 47 New patients
14 (30%) early death (including 4 considered too unfit for active treatment)
13 (28%) on long term dialysis
20 (42%) avoided or became dialysis independent
38 % reversal of dialysis dependency
Of 15 Relapsed patients
27 % early death
6.6% long term dialysis
66.6% dialysis avoided or reversed
88% reversal of dialysis dependency
13. Overall survival for myeloma patients has improved in the last decade since the use of high dose steroid containing regimes and novel therapies
14. Treatment of patients with myeloma renal failure by reducing the SFLC Physical removal
Switching off production
15. Physical removal Plasma exchange is theoretically beneficial in cast nephropathy,
Evidence from two early small randomised trials conflicting
(Zucchelli et al, 1988; Johnson et al, 1990)
No conclusive evidence that plasma exchange substantially reduced a composite outcome of death, dialysis dependence, or glomerular filtration rate <30 ml /min per 1.73 m2 at 6 months in randomized, controlled trial conducted in Canada between 1998 and 2004
(Clark et al 2005)
16. Reversibility of renal failure with high dose steroid containing regimes
73 % of 41 newly diagnosed patients
Increasing to 80 % with the addition of novel agents
Kastritis et al Haematologica 2007
19. Recruitment 79 patients randomised January 2004 to January 2009
20. Recruitment per centre
21. MERIT interim analysis of effect of SFLC on renal recovery
Malignant SFLC levels were significantly lower at entry in patients who were alive and dialysis free at 100 days
Greater percentage reductions in FLC in the first two weeks are associated with a higher probability of renal recovery
Maximum percentage reduction in malignant FLC levels in the first two weeks was variable and mostly achieved by 5 days.
median; 68.9 (range; -78 to +99)
ADF group; mean 74.1 sd 16.4
NADF mean; 44.6 sd 44.6.
Drayson et al Poster IMW 2009
22. It follows from MERIT data
that patients need to be identified earlier in the disease so FLC load is smaller
that treatment has to be directed at the most effective means of reducing the SFLC
23. Current Status of Trial. Data cleansing.
Your prompt return of information greatly appreciated.
Meeting of TMG imminent
Publication in 2010
24. Acknowledgements Patients and staff:
Aberdeen Royal Infirmary
Aintree Hospital NHS Trust
Bradford Teaching Hospitals NHS Trust
Glasgow Royal Infirmary/ Glasgow Western
Hope Hospital, Salford
Hull Royal Infirmary
Kent and Canterbury Hospital
William Harvey Hospital
Queen Elizabeth the Queen Mother Hospital
Leeds General Infirmary
Leicester General Hospital
Monklands Hospital, Airdrie
Oxford Radcliffe Hospital
Royal Cornwall Hospital
Royal Sussex Hospital, Brighton
Southmead Hospital, Bristol
St Georges Healthcare Trust
St Helier Hospital
University Hospital Coventry and Warwickshire NHS Trust
Victoria Royal Infirmary
Western General Hospital, Edinburgh
York District Hospital