1. Clinical profiles and outcomes in 1203 newly diagnosed patients with systemic AL amyloidosis: first analysis of the ALchemy study.
Richa Manwani

2. Systemic AL amyloidosis
Mahmood et al, Haematologica 2014

3. Systemic AL Amyloidosis

4. Methods
National referral centre for patients with amyloidosis in the UK
ALchemy study
A prospective study of all patients seen at the UK NAC diagnosed with systemic AL amyloidosis
Captures majority of the national caseload of amyloidosis in UK

5. Methods 1203 patients recruited from September 2009-March 2016
Study assessments: 3 months, 6 months and then 6 monthly
Imaging – echocardiogram, 123I serum amyloid P component (SAP) scintigraphy, CMR
Biochemical – serum albumin, serum creatinine, 24 hour urinary protein, liver function tests, cardiac biomarkers (troponin T, NT-proBNP)
Clonal response
Treatments and toxicity recorded
Organ and haematological response assessed by international amyloidosis consensus guidelines (Comenzo et al, Leukaemia 2012)
Survival calculated by Kaplan-Meier analysis.

6. Baseline characteristics
 n(%)/Median (Range)
Median age (years)
66.3 ( )
Sex
Male 58%/Female 42%
ECOG 0-2
ECOG 3-4
92% 8%
NYHA 1-2
NYHA 3-4
83%
17%
NT-proBNP (ng/L)
1974 ( )
LV wall thickness (mm)
12.5 (5-22.5)
Serum creatinine (µmol/L)
96 ( )
24 hour urinary protein (g/24h)
3.5 (0.1-58)
dFLC (mg/L)
181.7 ( )
M-protein
914 (75.9%)
Serum paraprotein > 5g/L
446 (37%)

7. 62 patients (5.2%) died before treatment.
First line treatment
62 patients (5.2%) died before treatment.

8. Overall survival in entire cohort
Deaths < 3 months: 162/1203 (13.5%)
Deaths 3-6 months:
98/1203 (8.1%)
Median survival 57 months
Overall survival
Median = 57 months

9. Progression free survival
Median progression free survival: 17 months
Progression free survival
Time (months)

10. Cardiac involvement remains the main determinant of survival
Mayo cardiac stage
Stage 1
Stage 2
Stage 3 (Median 12 months)
NYHA class
NYHA 1-2
(Median 83 months)
NYHA 3-4
(Median 6 months)
Log rank p <0.001
Log rank p <0.001
Median survival of stage 3b (NT-proBNP >8500ng/L) = 5 months

11. Haematological response at 6 months

12. dFLC response (ITT) by treatment regime%

13. 6 month overall haematological responseCR
VGPR CR PR
VGPR: 54 mths
No response (median survival 8 months)
PR: 20 mths
Log Rank p = <0.001
No response (5 months)
OS dFLC response: VGPR or better 29 mths, PR 26 mths, no response 9 mths

14. Treatment type Log Rank p = 0.503 Bortezomib 83 months
Melphalan 14 months
Bortezomib 83 months
IMID 55 months
Log Rank p = 0.503
IMID 15 months
Log rank p=0.061

15. Time to next treatment
Median time to next treatment: 55 months

16. TNT based on dFLC

17. Organ response at 6 months (ITT basis)

18. Organ response
p=0.2
p=0.006
p=0.0293
p=0.0364

19. Six minute walk test - new method of measuring outcomes?
Median:
417m m m
Median change from baseline:

20. Six minute walk test - new method of measuring outcomes?
Impact of change in 6M-Walk at 6 months on survival
>378 m m
<260 m; median 13 months
Log Rank p = <0.001
Impact of Baseline 6M-Walk on survival
Log Rank p = 0.07

21. Independent predictors of survival
Hazard Ratio
P value CI
Mayo Stage 1
Ref
<0.0001
Mayo Stage 2
1.8
0.002
Mayo Stage 3a
2.2
Mayo Stage 3b
3.2
SBP <100 mmHg
1.3
0.006

22. Independent predictors of survival
Hazard Ratio
P value CI
Mayo Stage 1
Ref
<0.015
Mayo Stage 2
2.03
0.066
Mayo Stage 3a
1.99
0.07
Mayo Stage 3b
3.06
0.005
6M walk distance(>378 m)
REF
6M walk distance ( m)
1.05
0.80
6M walk distance (<260m)
1.5
0.02

23. Conclusion Data from this large real-world cohort shows:
Overall survival has improved, with median approaching 5 years
Bortezomib associated with highest OS and PFS in cohort.
However, high early death remains a persistent problem.
Less than a fifth of all patients achieve a “true” CR, but 40% reach a dFLC VGPR or better.
Organ responses on an intention-to-treat basis remain extremely disappointing, highlighting the need for anti-amyloid therapies.
Achieving a CR translates into better overall survival and organ response.
Six minute walk test distance of <260m is an independent marker of poor outcome.