Health-related quality of life in acute myeloid leukemia patients not eligible for intensive chemotherapy: results of a systematic literature review

Figures & data

Figure 1 PRISMA flow diagram

Table 1 Study eligibility criteria

Element	Inclusion	Exclusion
Patient population	• Adults (≥18 years) • Newly diagnosed with AML or high risk MDS • Not eligible for IC	• Nonhuman • Refractory/relapsed AML • AML treated with IC
Intervention and comparators	• Glasdegib • Azacitidine • Decitabine • Cytarabine (low dose) • Hydroxycarbamide • 6-Mercaptopurine • Etoposide • BSC	• Studies not including any therapies of interest • Stem cell transplantation studies • Surgery studies • Radiotherapy studies
Outcomes measures	• Any HRQoL outcome • Utilities/disutilities/QALYs for health states or adverse events	• Studies not including at least one of the outcomes listed in the inclusion criteria
Study design	• Reports of randomized clinical trials assessing HRQoL • Development and/or validation of HRQoL measures • Observational studies measuring PROs • Retrospective chart audits and database analyses reporting PROs • Patient surveys reporting PROs • Reports of mapping exercises for any outcome measure to utility • Reports of utility elicitation exercises • Reports of utility validation exercises • Reports of economic evaluations using utility measures elicited during studies • Studies that present data via a validated scale • Systematic reviews and meta-analyses (to be used for reference cross-checking only)	• Reviews • Editorials • Notes/comments/letters
Restrictions	• Published in the English language • Year limitations: 2007 to present	• Published in a non-English language

a Note: Utility studies were not limited to AML noneligible for IC.

Abbreviations: PROs, patient-reported outcomes; QALY, quality-adjusted life year.

Table 2 Included studies

References	Interventions	Type of study/study population	Scales used	QoL summary
Minden et al^Citation26 (abstract); Dombret et al^Citation9	AZA vs CCR (standard induction chemotherapy, low-dose cytarabine, or supportive care only)	RCT, N=488; age ≥65 years, newly diagnosed AML, not eligible for HSCT	EORTC QLQ-C30	157 AZA patients and 134 CCR patients were evaluable for HRQoL. AZA or CCR showed general improvement in the four relevant domains. No HRQoL detriment was seen with AZA or CCR at the group level during treatment. “Few” statistically significant (P<0.05). “Fewer” met the MID threshold. CCR achieved meaningful improvement in fatigue (cycles 7 and 9) and GHS/QoL (cycle 9). Patients receiving AZA achieved meaningful improvement in fatigue (cycle 9). Scores varied substantially among individual patients in both treatment groups
Oliva et al^Citation24 (abstract)	AZA vs BSC after conventional induction (3+7) and consolidation chemotherapy	RCT, N=99; age >60 years, newly diagnosed or secondary AML (>30% myeloid marrow blasts), ECOG PS <3	EORTC QLQ-C30, QoL-E (ver 3)	After first "3+7" regimen; QoL-E: no changes; QLQ-C30: deterioration in PF (median 80, IQR 60–93, to 67, IQR 52–87, P=0.008), role function (median 83, IQR 67–100, to 67, IQR 33–83, P=0.023), and GHS (median 50, IQR 33–69, to 67, IQR 50–75, P=0.002) and improvement in dyspnea (P=0.023). After consolidation therapy, among patients obtaining a CR QoL-E: improvement in median physical scores (56, IQR 41–72, to 63, IQR 50–84, P=0.033), disease-specific domain scores (59, IQR 48–67, to 74, IQR 67–85, P=0.003), and treatment outcome index scores (55, IQR 32–77, to 79, IQR 41–86, P=0.026); QLQ-C30: improvement in emotional function (83, IQR 67–92, to 92, IQR 77–100, P=0.015), GHS (median 50, IQR 33–65, to 67, IQR 58–83, P=0.002). Dyspnea and insomnia regressed while financial problems increased
Lübbert et al^Citation17	DEC + BSC vs BSC	RCT, N=233; Age ≥60, MDS or CMML, int-1, int-2, or high-risk, ineligible for intensive treatment, ECOG ≤2	EORTC QLQ-C30	Patients on the DEC arm showed a significant improvement in their physical functioning and borderline improvement in GHS. No apparent effect was seen on dyspnea. Trends of most of QoL scales favors DEC
Sekeres et al^Citation25	LDAC + lintuzumab vs LDAC	RCT, N=211; age ≥60 years, de novo AML, exposed to chemotherapy for different malignancies, ECOG PS ≤2	FACT-Leu	No consistent pattern of change in FACT-Leu score was observed. The median change in FACT-Leu score was similar in both arms where the range of scores overlapped considerably
Tseng et al^Citation27 (abstract)	AZA	Prospective observational, N=56; MDS, treated with AZA	EORTC QLQ-C30, FACT-fatigue, EQ-5D, and a global fatigue scale	50 were evaluable for QoL. Clinically important differences were seen in physical, role, cognitive, and social functioning, GHS between responders and nonresponders (all higher in responders). Responders had significantly superior GHS (P=0.001) and EQ-5D scores (P=0.0002) and lower levels of fatigue (P<0.0001)
Ingber et al^Citation28 (abstract)	AZA	Prospective observational, N=20; MDS, treated with AZA	EORTC QLQ-C30, EQ-5D, global fatigue scale	The only clinically significant improvements were observed with the EORTC physical functioning and fatigue subscales but constipation scores were higher and GHS/QoL deteriorated over time.
Oliva et al^Citation29	Intensive therapy vs palliative treatment	Prospective observational, N=113; age ≥60, newly diagnosed de novo AML	EORTC QLQ-C30 (ver. 3) and QoL-E (ver. 2)	At diagnosis, the median QoL-E general standardized score 54 (IQR 46–70)/median EORTC QLQ-C30 global score decreased 50 (IQR 41–66) Fatigue in QoL-E median 45 (IQR 32–53)/QLQ-C30 median 33 (IQR 22–66) Loss of appetite was perceived by 75% of patients
Deschler et al^Citation30	BSC vs (HMA vs IC + HCT	Patient survey, N=195	EORT QLQ-C30 and ADL (Barthel index)	At baseline, median EORTC QLQ-C30 fatigue (BSC vs HMA vs IC/HCT vs total): 53.3 vs 66.6 vs 44.3 vs 53.3, median ADL (Barthel index) (BSC vs HMA vs IC/HCT vs total): 100 vs 100 vs 100 vs 100
Pandya et al^Citation31 (abstract)	NA	Patient survey, N=75; AML, 1L or R/R (75% [n=56] first line vs 25% [n=19] relapsed/refractory AML)	FACT-Leu and EQ-5D-3L	First-line patients may have a directionally better QoL scores than those on later lines of therapy 1L vs R/R: EQ-5D =0.75 vs 0.71 (P=0.51) and the FACT-Leu =103.7 vs 92.5 (P=0.098). R/R patients were significantly more likely than first-line patients to be affected physically by their AML condition 1L vs R/R: FACT-Leu-physical well-being sub-domain =13.0 vs 17.6, P=0.005
Cheng et al^Citation34 (abstract)	NA	Patient survey, N=18; AML, achieved the first CR	EORTC QLQ-C30, QoL-CS, FACIT-fatigue, and HADS	Participants scored well on the EORTC QLQ-C30. The FACIT-fatigue (worst 0 to best 52) mean score was 28.7 and the median score was 33.5 (normal ≥30). On the HADS anxiety scale, two participants scored in the abnormal range. On the QoL-CS, participants scored above 6/10 in all domains, with exceptions of the psychological subscales of distress and fear (physical 8.7/psychological 7.9/distress 4.7/fear 4.5/social 7.1/spiritual 7.4)
Leunis et al^Citation14	NA	Patient survey, N=92; AML survivors vs general population	EQ-5D and EORTC QLQ-C30	The majority of the patients with AML reported problems on the five functioning scales of the QLQ-C30. The average scores on all functioning scales were significantly lower in patients with AML compared to adjusted general population scores. The differences in physical, role, cognitive, and social functioning were also clinically relevant. Despite these differences, no significant difference was found for the global quality of life
Levy et al^Citation33	AZA vs CCR (BSC alone, low-dose chemotherapy + BSC, and standard-dose chemotherapy + BSC)	Utility, CEA; AML survivors vs general population	EQ-5D mapped from EORTC QLQ-C30 and SF-6D mapped from SF-12	The utility analysis results show that, compared with patients receiving BSC, patients treated with AZA had a better quality of life and the difference increased with increasing length of treatment

Note: SF-6D and SF-12, short form health surveys.

Abbreviations: ADL, activities of daily living; AZA, azacitidine; CEA, cost-effectiveness analysis; CCR, conventional care regimens; CMML, chronic myelomonocytic leukemia; CR, complete response; DEC, decitabine; ECOG PS, The Eastern Cooperative Oncology Group performance status; EQ-5D-3L, EuroQol 5-dimensions 3-levels; FACT-fatigue, Functional Assessment of Cancer Therapy-fatigue; FACT-Leu, Functional Assessment of Cancer Therapy-leukemia; HADS, Hospital Anxiety and Depression Scale; HCT, hematopoietic cell transplantation; HSCT, hematopoietic stem cell transplantation; MID, minimally important difference; NA, Not applicable; QoL, quality of life; QoL-CS, quality of life cancer survivor; RCT, randomized clinical trials; R/R, relapsed/refractory.

Figure 2 Impact of HRQoL in NIC AML

Table S1 Search strategy

1	exp LEUKEMIA, MYELOID, ACUTE/	79,787
2	exp LEUKEMIA, MYELOID/	180,001
3	exp ACUTE DISEASE/	323,400
4	2 and 3	9,745
5	LEUKEMIA, MYELOID/	33,612
6	ACUTE DISEASE/	323,400
7	5 and 6	7,711
8	(acut$ or akut$ or agud$ or aigu$).tw,kf,ot.	2,725,487
9	((myelo$ or mielo$ or nonlympho$ or granulocytic$) and (leuk?em$ or leuc$)).tw,kf,ot.	233,145
10	8 and 9	136,561
11	aml.tw,kf,ot.	82,861
12	(Acute Myeloid Leukemia$ or Leukemia$, or Leukaemia$ or Acute Myeloid or Myeloid Leukemia$, Acute).af.	787,634
13	(Leukemia$, Laukaemia$, Myelo$, Acute or Myelo$ Leukemia$, Acute or Acute Myelo$ Leukemia$).af.	100,183
14	(Leukemia$, Nonlympho$, Acute or Nonlympho$ Leukemia$, Acute or Acute Nonlympho$ Leukemia$).af.	5,775
15	(Leukemia$, Leukaemia$, Granulo$, Acute or Granulo$ Leukemia$, Acute or Acute Granulo$ Leukemia$).af.	53,759
16	or/12–15	787,634
17	1 or 4 or 7 or 10 or 11 or 16	798,957
18	(glasdegib or azacitidine or decitabine or low dose cytarabine or LDAC or hydroxycarbamide or 6-mercaptopurine	72,222
	or etoposide or best supportive care).ti,ab
19	17 and 18	16,693
20	Quality of Life/	573,654
21	(QOL or HRQL or HRQOL).ab,ti	139,382
22	(patient adj2 reported adj2 outcome adj2 measure$).ti,ab	139,382
23	(utility or utilities).ti,ab	425,239
24	utility measure$.ti,ab	1,380
25	“quality of life”.de	573,654
26	“quality adjusted life year”.de	20,701
27	quality adjusted life year/	36,275
28	(quality adj4 life).ti,ab	651,934
29	(qol or “disability adjusted life”).ti,ab	103,635
30	(qaly* or qald* or qale* or qtime* or daly*).ti,ab	32,294
31	(euroqol or eq5d or “eq 5d” or “eq5d” or “euro qual” or “euro qol” or euroqual).ti,ab	26,629
32	(EORTC$ or European Organi$ation for Research and Treatment of Cancer).ti,ab	7,383
33	(willingness adj4 pay).ti,ab	11,776
34	(standard adj1 gamble*).ti,ab	2,015
35	((“time trade” adj1 off*) or (time adj1 tradeoff*) or tto or timetradeoff).ti,ab	4,369
36	(TTO or SG or WTP).ti,ab	27,036
37	((valu* or measur*) adj4 (health or outcome or outcomes or effect or effects or change* or state*)).ti,ab	1,088,035
38	(preference* adj4 (patient* or public or valu* or measur*)).ti,ab	51,709
39	(multiattribute* adj1 (health or theor* or analys* or utilit*)).ti,ab	356
40	((multi adj1 attribute*) and (attribute* adj1 theor*)).ti,ab	3
41	((multi adj1 attribute*) and (attribute* adj1 analys*)).ti,ab	17
42	((multi adj1 attribute*) and (attribute* adj1 utilit*)).ti,ab	391
43	(utilit* adj4 (valu* or measur* or health or life or estimat* or elicit* or disease)).ti,ab	32,190
44	((symptom or symptoms) adj5 (score* or scale* or instrument* or measur*)).ti,ab	179,539
45	(FACT-G or “EORTC QLQ-C-30” or FLIC or QLI-CV).tw.	4,589
46	functional assessment of cancer therapy.tw.	5,456
47	or/20–46	2,411,950
48	19 and 47	809
49	(letter or editorial or comment or news or newspaper article).pt.	3,485,218
50	animals/not (humans/and animals/)	35,974
51	case reports/	2,029,566
52	in vitro.pt	3
53	or/49–52	11,256,953
54	48 not 53	798
55	limit 54 to Humans	720
56	limit 55 to English	680
57	limit 56 to 2007–present	507
58	Deduplicate	396

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