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

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Presentation transcript:

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 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

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.

Baseline characteristics n(%)/Median (Range) Median age (years) 66.3 (29.5-89.4) 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 (16-147940) LV wall thickness (mm) 12.5 (5-22.5) Serum creatinine (µmol/L) 96 (26-1124) 24 hour urinary protein (g/24h) 3.5 (0.1-58) dFLC (mg/L) 181.7 (0-15898) M-protein 914 (75.9%) Serum paraprotein > 5g/L 446 (37%)

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

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

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

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

Haematological response at 6 months

dFLC response (ITT) by treatment regime %

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) OS dFLC response: VGPR or better 29 mths, PR 26 mths, no response 9 mths

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

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

TNT based on dFLC

Organ response at 6 months (ITT basis)

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

Six minute walk test - new method of measuring outcomes? Median: 417m 389m 411m Median change from baseline:

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

Independent predictors of survival Hazard Ratio P value CI Mayo Stage 1 Ref <0.0001 Mayo Stage 2 1.8 0.002 1.2-2.6 Mayo Stage 3a 2.2 1.5-3.2 Mayo Stage 3b 3.2 2.2-4.7 SBP <100 mmHg 1.3 0.006 1.08-1.6

Independent predictors of survival Hazard Ratio P value CI Mayo Stage 1 Ref <0.015 Mayo Stage 2 2.03 0.066 0.9-4.3 Mayo Stage 3a 1.99 0.07 0.9-4.2 Mayo Stage 3b 3.06 0.005 1.4-6.6 6M walk distance(>378 m) REF 6M walk distance (378-261m) 1.05 0.80 0.7-1.5 6M walk distance (<260m) 1.5 0.02 1.06-2.3

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.