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Richa Manwani 9.11.2017

3 Clinical profiles and outcomes in 1203 newly diagnosed patients with systemic AL amyloidosis: first analysis of the ALchemy study. Richa Manwani 9.11.2017. Systemic AL amyloidosis. Mahmood et al, Haematologica 2014. Systemic AL Amyloidosis. Methods.

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Richa Manwani 9.11.2017

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  1. 3Clinical profiles and outcomes in 1203 newly diagnosedpatients with systemic AL amyloidosis: first analysis of the ALchemystudy. • RichaManwani 9.11.2017

  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

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

  11. Haematological response at 6 months

  12. dFLC response (ITT) by treatment regime n=24 n=8 n=301 n=503 n=43 %

  13. 6 month overall haematological response CR VGPR CR PR VGPR: 54 mths No response (median survival 8 months) PR: 20 mths Log Rank p = <0.001 No response (5 months)

  14. Treatment type Bortezomib 83 months Bortezomib 21 months IMID 55 months Log Rank p = 0.503 IMID 15 months Log rank p=0.061 Melphalan 14 months Log rank p=0.04

  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 change from baseline: Median: 417m 389m 411m

  20. Six minute walk test - new method of measuring outcomes? Impact of change in 6M-Walk at 6 months on survival Impact of Baseline 6M-Walk on survival >378 m 261-377 m <260 m; median 13 months Log Rank p = 0.07 Log Rank p = <0.001

  21. Independent predictors of survival

  22. Independent predictors of survival

  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.

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