An observational, non-interventional study for the follow-up of patients with amyloidosis who received miridesap followed by dezamizumab in a phase 1 study

Richards, Duncan; Millns, Helen; Cookson, Louise; Lukas, Mary Ann

doi:10.1186/s13023-022-02405-7

Orphanet Journal of Rare Diseases

Table 3 Classification of patients in this analysis

From: An observational, non-interventional study for the follow-up of patients with amyloidosis who received miridesap followed by dezamizumab in a phase 1 study

Patient	Amyloid type	Classification	Basis of classification
Patient	Amyloid type	Classification	Evidence for response in parent study	Evidence for sustained response	Evidence for declining/lack of response
ORGAN: LIVER
107	AL	Sustained responder	↓ Total amyloid load on SAP scan ↑ eGFR (small)	↓ GGT Stable eGFR Stable total amyloid load on SAP scan ↑ 6MWD Stable FLC κ:λ	–
109	ApoA1	Declining responder	↓ Total amyloid load on SAP scan ↓ GGT		Worsening amyloid load on SAP scan ↑ GGT after 1 year ↑ Total amyloid load after 1 year ↓ eGFR after 1 year
110*	AL	Sustained responder	↓ hepatic amyloid load on SAP scan ↓ GGT	Stable total amyloid load on SAP scan Stable GGT
111^†	AL	Declining responder	↓ hepatic amyloid load on SAP scan (1st treatment)		↓ eGFR after 1 year (with associated ↑ NT-proBNP) ↑ GGT after 1 year Death
114^‡	AL	Declining responder	↓ hepatic amyloid load on SAP scan ↓ GGT	Fluctuating amyloid load on SAP scan (worsening/better) Stable GGT	Variable total amyloid load ↓ eGFR after 2 years (with associated small ↑ NT-proBNP)
115	AL	Declining responder	↓ splenic amyloid load on SAP scan	Stable or better amyloid load on SAP scan Stable GGT	↓ eGFR (with associated small ↑ NT-proBNP) ↓ 6MWD
116	AL	Sustained responder	↓ splenic and hepatic amyloid load on SAP scan ↓ GGT	↓ GGT ↓ Total amyloid load on SAP scan (transient) ↑ 6MWD (transient)	–
119	AL	Non-responder	–	Stable eGFR Stable GGT ↑ 6MWD (slight)	Variable FLC κ:λ
ORGAN: LIVER AND KIDNEY
108	AL	Sustained responder	↓ Total amyloid load on SAP scan ↓ GGT	Stable total amyloid load on SAP scan ↓ GGT ↑ 6MWD Stable eGFR Stable FLC κ:λ	–
113^§	AL	Sustained responder	↓ Total amyloid load on SAP scan	↓ Total amyloid load on SAP scan Stable eGFR
ORGAN: KIDNEY
001	AA	N/A (non-therapeutic dose in FIHS)	N/A	N/A	N/A
012	AA	Sustained responder	↓ Renal amyloid load on SAP scan Stable eGFR	Stable total amyloid load on SAP scan Stable eGFR, stable 6MWD	–
102	AFib	Declining responder	↓ Total amyloid load on SAP scan	Stable total amyloid load on SAP scan	↓ eGFR to end stage renal disease after 2 years; double renal transplant after 3 years (with associated ↑ NT-proBNP)
104	AFib	Declining responder	↓ Splenic and renal amyloid load on SAP scan		↑ Amyloid load after ~ 3 years ↓ eGFR after 2 years (with associated ↑ NT-proBNP)
105	AFib	Declining responder	↓ Renal amyloid load on SAP scan		↓ eGFR
106	AFib	Declining responder	↓ Renal amyloid load on SAP scan	Stable total amyloid load on SAP scan Stable eGFR	↓ 6MWD
117	AFib	Declining responder (declined at 3 year)	↓ Total amyloid load on SAP scan	Stable total amyloid load on SAP scan	↓ eGFR (dialysis considered)
ORGAN: CARDIAC
118^¶	AL	Declining responder	↓ Splenic amyloid load on SAP scan (none detected after treatment)		Reoccurrence of small amyloid load on SAP scan ↑ NT-proBNP after 2 years ↑ GGT after 2 years ↓ 6MWD Variable FLC κ:λ
123	ATTR (hereditary)	Non-responder	–	–	↑ NT-proBNP Death
124	ATTR (wild-type)	Non-responder	–	–	↑ NT-proBNP
125	ATTR (wild-type)	Non-responder	–	–	↑ NT-proBNP with AF
ORGAN: CARDIAC AND KIDNEY
120	AL	Non-responder	–	–	↑ GGT (slight) ↑ NT-proBNP at 7 months ↓ eGFR at 7 months Death
121	AL	Sustained responder	↓ LV mass on MRI scan ↓ splenic amyloid load on SAP scan (none detected after treatment)	↓ NT-proBNP stable (outside normal range)

Detailed information on response classification is given in the methods section. Decisions regarding response status were guided by the criteria listed in Table 1. Responses were classified by a clinical scientist and reviewed by a study physician; response classification accounted for the organ site(s) involved. Sustained responders showed a response in the FIHS, maintained over the follow-up period; declining responders showed a response in the FIHS, not maintained over the follow-up period; non-responders showed no response in the FIHS or during the follow-up period
*Patient 110 experienced clonal collapse during the FIHS, ~ 2 months after first treatment session. During follow-up FLC κ:λ started to fall ~ 31 months after the last treatment session, indicating relapse; treatment was received
^†Patient 111 experienced clonal relapse in the FIHS after first treatment session in study; ~ 1 year after the study, GGT and NT-proBNP significantly increased with a decline in eGFR, at which time the patient received treatment for clonal relapse
^‡Patient 114 experienced clonal relapse during the FIHS and during the follow-up period; their amyloid load varied due to these relapses
^§During the FIHS, patient 113 had clonal relapse between treatment sessions as evidenced by high FLC κ:λ ratio; the patient underwent treatment and FLC κ:λ improved
^¶Patient 118 experienced clonal relapse during follow-up (increase in FLC and fall in FLC κ:λ ratio); treatment was administered
6MWD, 6-min walking distance; AA, serum amyloid A; AF, atrial fibrillation; AFib, fibrinogen A alpha-chain; AL, immunoglobulin light chain; ApoA1, apolipoprotein A-I; ATTR, transthyretin; eGFR, estimated glomerular filtration rate; FLC, free light chain; GGT, gamma-glutamyl transferase; NT-proBNP, N-terminal-pro B-type natriuretic peptide

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ISSN: 1750-1172

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