A systematic review of clinical effectiveness and safety for historical and current treatment options for metachromatic leukodystrophy in children, including atidarsagene autotemcel

Armstrong, Nigel; Olaye, Andrew; Noake, Caro; Pang, Francis

doi:10.1186/s13023-023-02814-2

Orphanet Journal of Rare Diseases

Table 3 Summary of survival data

From: A systematic review of clinical effectiveness and safety for historical and current treatment options for metachromatic leukodystrophy in children, including atidarsagene autotemcel

Treatment	MLD type	Symptom status	Time point	n	% survival	Source
Atidarsagene	LI	Pre-symp	Median follow-up 3.0 (1.0–7.5) years	16/16	100	Fumagalli et al. [13]
	LI	Pre-symp	6 years of age	7/16	100%	Fumagalli et al. [13]
	EJ	Mixed	9 years of age	NR/11	75.5	Fumagalli et al. [13]
	EJ	Mixed	10 years of age	NR/11	75.5	Fumagalli et al. 2022 [13]
	EJ	Mixed	11 years of age	NR/11	75.5	Fumagalli et al. [13]
HSCT	Child	NR/unclear	1 year	NR/NR	65	Prasad [24]—P
	Child	NR/unclear	5 year	NR/NR	57	Prasad [24]—P
	Child	Mixed	NR⁺	8/8	100	Bohringer [19]—NR*
	LI to LJ^c	NR/unclear	Last follow-up (NR)	5/7	72.4	van Rappard [17]—R
	LI to LJ^c	Mixed	5 year	20/27	74.1 (95% CI 53.2–86.7)	Martin [23]—R
	LI to J	Mixed	NR/unclear	16/31	51.6	Boucher [21]—R
	LI	NR/unclear	1 year	1/2	50	van Rappard [17]—R
	LI	Mixed	5 years	NR/NR	50	Boucher [21]—R
	LI	Mixed	5 years	6/10	60 (95% CI 25.3–82.7)	Martin [23]—R
	LI	Mixed	6 years	NR/NR	59	EUROCORD [22]—R
	EJ	Mixed	6 years	NR/NR	80	EUROCORD [22]—R
	J	NR/unclear	1 year	4/5	80	van Rappard 2016 [17]—R
	J	Mixed	5 years	14/17	82.4 (95% CI 54.7–93.9)	Martin [23]—R
	J	Mixed	5 years	NR/NR	59 (95% CI 38–75)	Boucher [21]—R
	J	Mixed	5 years⁺⁺	19/24	79.2	Groeschel [16]^—R*
	LJ^c	Mixed	6 years	NR/NR	79	EUROCORD [22]—R
	J	Mixed	Median 7.5 (3.0–19.7) years	18/24	75	Groeschel [16]—R*
	J	Mixed	NR	6/9	66.7	Bley [18]—R*
Standard care	Child	NR/unclear	At study analysis (NR)	8/11	72.7	Singh [20]—R
	LI to LJ^c	NR/unclear	Last follow-up (22–93 months)	11/19	57.9	van Rappard [17]—R
	LI	Pre-symp	6 years of age	5/19	70.8 (95% CI 43.6–86.7)	Fumagalli et al. [13]
	LI	NR/unclear	Last follow-up (19–93 months^)	2/6	33.3^a	van Rappard [17]—R
	LI	NR/unclear	Last follow-up (NR)**	3/16	18.8^d	LDM/1 study [25]—R/P
	LI	NR/unclear	5 years	NR	56	LDM/1 study [25]—R/P
	LI	NR/unclear	10 years	NR	40	LDM/1 study [25]—R/P
	EJ	Mixed	9 years of age	12/12	100 (95% CI 100–100)	Fumagalli et al. [13]
	EJ	Mixed	10 years of age	11/12	88.9 (95% CI 43.3–98.4)	Fumagalli et al. [13]
	EJ	Mixed	11 years of age	9/12	76.2 (95% CI 33.2–93.5)	Fumagalli et al. [13]
	EJ	NR/unclear	Last follow-up (NR)**	6/9	66.7^e	LDM/1 study [25]—R/P
	EJ	NR/unclear	5 years	NR	90	LDM/1 study [25]—R/P
	EJ	NR/unclear	10 years	NR	80	LDM/1 study [25]—R/P
	LJ	NR/unclear	Last follow-up (NR)**	4/4	100^f	LDM/1 study [25]—R/P
	LJ	NR/unclear	5 years	NR	100	LDM/1 study [25]—R/P
	LJ	NR/unclear	10 years	NR	100	LDM/1 study [25]—R/P
	J	Mixed	5 years⁺⁺	41/41	100	Groeschel [16]—R*
	J	NR/unclear	Last follow-up (NR)	9/13	69.2^b	van Rappard [17]—R

Mixed symptom status refers to population including both pre-symptomatic and symptomatic patients
EAP expanded access programme, I infantile MLD, J juvenile MLD, EJ early juvenile MLD, LJ late juvenile MLD, HSCT haemopoietic stem cell transplantation, MLD metachromatic leukodystrophy, mth month, n number alive, N total number analysed, NR not reported, P prospective study, Pre-symp pre-symptomatic, R retrospective study, yr year
*Indicates that there is a possibility of overlap with populations reported in other studies based in German study centres and/or using the LEUKONET database
**Indicates that there is an overlap between patients with the Fumagalli et al. [13] NHx cohort
Values in italics are reported to be Kaplan Meier % survival values
Time point is reported as described by the author(s), where possible the baseline from which time is measured is stated: ⁺After treatment (NR); ⁺⁺After disease onset
^aPatients died aged 4, 5, 6 and 8 years of age
^bPatients died aged 8, 11, and 12 (n = 2) years of age
^cLJ disease is no longer relevant to the indication for Atidarsagene treatment
^dThirteen patients died due to disease progression. Sex patients (overall n = 22) were lost to follow-up
^eThree patients died due to disease progression. Five patients (overall n = 14) were lost to follow-up
^fOne patient (overall n = 5) was lost to follow-up

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ISSN: 1750-1172

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