Health-related quality of life and economic burden of chronic lymphocytic leukemia in the era of novel targeted agents

Figures & data

Figure 1. PRISMA flowchart of the HRQoL burden review of CLL. Abbreviations. CA, conference abstract; CLL, chronic lymphocytic leukemia; HRQoL, health-related quality of life; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SGA, subgroup available; SLR, systematic literature review.

Table 1. Overview of studies included in the HRQoL burden review of CLL.

Study name	Number of patients	Country	Study design	Data source	Setting	Treatment naïve/treated (active/previously)	QoL scale	Findings/conclusions
Holzner 2001^20	81 with CLL	Austria	NR	Outpatient unit of the Department of Haematology and Oncology, Innsbruck University Hospital	Single center	NR	EORTC QLQ-C30, FACT-G	Corresponding subscales of EORTC-QLC-C30 and FACT-G showed low to moderate intercorrelations across all four groups of patients (with breast cancer, Hodgkin’s disease, bone marrow transplantation, and CLL) studied. A comparison of pairs highlighted substantial differences in corresponding subscales of EORTC QLQ-C30 and FACT-G
Holzner 2004^15	76	Austria	Longitudinal	Outpatient unit of the Department of Haematology and Oncology, Innsbruck University Hospital	Single center	NR	EORTC QLQ-C30	Compared with healthy controls, patients with CLL reported lower QoL in almost all domains. No difference observed between patients who had already received chemotherapy and those who had not. Female patients were found to have lower QoL scores in the areas of emotional and social functioning than males
Levin 2007^21	107	USA	Cross-sectional	CLL research database	Unclear	Treatment naive (54.3%)/treated (45.7%)	FACT-G, FACT-Lym, BAI, BDI-II, SF-36 Health Survey v2	Patients ≤60 y had worse QoL on the SF-36 Mental Component Score (p = .0001), FACT-G (p = .060), BDI (p = .014), and on several subscales. Patients ≤60 y had better QoL on the SF-36 Physical Component (p = .001) and Physical Functioning (p = .009)
Shanafelt 2007^16	1482	35 Countries (81% in USA)	Retrospective	Web-based survey	Multicenter	Treatment naive (60.7%)^a/treated (40.3%)	BFI, FACT-G	Physical, social/family, functional, and overall QoL scores of patients with CLL were similar or better than published population norms. Emotional wellbeing scores of CLL were dramatically lower than the general population (p < .001) and patients with other types of cancer (p < .001)
Pashos 2012^24	899	USA	Prospective, observational	Connect CLL, a prospective, observational registry	Multicenter	Treatment naive and treated; numbers NR	BFI, EQ-5D, FACT-G, FACT-Leu	No significant differences between age groups (<65, 65–74, >74 y) in fatigue (BFI) or differences in overall HRQoL (EQ-5D). Overall QoL was better among 65–74 y cohort than either younger or older patients (FACT-Leu; p = .0421). FACT-G scores were similar among older age groups and better than the younger patients (p = .0275)
Pashos 2011^23	604	USA	Prospective, observational	Connect CLL, a prospective, observational registry	Multicenter	NR	BFI, EQ-5D, FACT-Leu	Fatigue, fatigue severity, and fatigue-related interference worsen by ECOG severity (BFI; all p< .0001). Mean EQ-5D worsens by ECOG severity (p < .0001). FACT-Leu domains (except social/family) were statistically worse with worse ECOG PS and in patients with fatigue
Kay 2012^22	1005	USA	Prospective, observational	Connect CLL, a prospective, observational registry	Multicenter	NR	BFI, EQ-5D, FACT-G, FACT-Leu	Total FACT-Leu, FACT-G, total EQ-5D Index and VAS results consistently suggested that patients initiating first-line therapy have better HRQoL compared with those initiating subsequent lines of therapy
Pashos 2013^26	1140	USA	Prospective, longitudinal, observational	Connect CLL, a prospective, observational registry	Multicenter	Treated (100%)	BFI, EQ-5D, FACT-G, FACT-Leu	Women reported worse global fatigue (p < .0001), fatigue severity (p < .0001), and fatigue-related interference (p = .0005) vs. men (BFI). Mean FACT-Leu total score was better among men vs. women (p = .0223)
Pashos 2012^25	899	USA	Prospective, observational	Connect CLL, a prospective, observational registry	Multicenter	NR	BFI, EQ-5D, FACT-Leu	BFI: women reported worse average global fatigue (p = .0003), fatigue severity (p < .0001), and fatigue-related interference (p = .0016). EQ-5D (p = .6775) and FACT-Leu (p = .1467) overall QoL scores did not differ by gender
McCarrier 2014^27	50	USA	Web-based survey	Social media-based patient networks	Unclear	Treatment-naive (62%)/treated (36%)	NR	In patients with CLL, fatigue was the most frequently expressed symptom (40%), followed by tiredness (38%), night sweats (38%), swollen lymph nodes (32%), and frequent infections (28%). Among impacts of CLL, worry and fear (66%), depressed feelings (52%), and work limitations (50%) were noted most frequently
Mudondo 2014^30	205 (94 responded)	UK	NR	NHS trusts	Single center	Treatment status NR	QoL scale (psychological wellbeing)	Overall anxiety levels were low and patient QoL was similar amongst patients with CLL, regardless of management setting
Hahn 2015^28	40	Germany	Cross-sectional	NR	Single center	Patients had undergone stem-cell transplantation (100%) [median of three previous treatments]	FACT-BMT questionnaire	Median FACT-BMT total score was 122, implying half of patients reported a good-to-excellent aggregated QoL and the other half an intermediate-to-good aggregated QoL at time of assessment
Holtzer-Goor 2015^17	144	The Netherlands	Longitudinal, observational	NR	Multicenter	Treatment-naïve (41%)/treated (59%)	EORTC-QLQ-C30 (+CLL16 module), EQ-5D, VAS	Patients with CLL differed from the general population on role functioning, fatigue, concerns about future health, and not having enough energy. Once treatment was indicated, HRQoL became considerably compromised
Buzaglo 2016^18	233	USA	Cross-sectional	Cancer Experience Registry	Unclear	NR	Distress level scale; perceived impact of CLL	High-risk patients with CLL experienced greater overall distress and depression risk at the time of survey response compared with patients at low or intermediate risk
Buzaglo 2017^19	134	USA	Cross-sectional	Cancer Experience Registry	Unclear	NR	PROMIS	“Watch and wait” or disease remission: no significant associations observed; worse anxiety was significantly associated with active treatment, whether first-line or subsequent therapy; second or subsequent line of therapy: significantly associated with worse physical and social functioning, and greater levels of fatigue, depression, and sleep disturbance
Williams 2018^29	125	NR	NR	NR	Unclear	NR	Anxiety (STAI), depression (CES-D)	Older age was associated with better STAI and CES-D scores, and each 1-y increase was associated with a 9% decrease in odds of anxiety and a 7% decrease in odds of depression. An ECOG grade of 3 or 4 was a significant predictor of increased depression risk and worse CES-D scores but not of anxiety. Overall, ≥20% of patients had clinically meaningful anxiety or depression (11% had both)
Yu 2018^14	306 (8 with CLL)	China	Cross-sectional	3 hospitals in China’s Heilongjiang province	Multicenter	NR	EQ-5D-3L	Family caregivers of patients with leukemia had lower health utility scores than the general population (p < .001)

Shaded rows represent studies linked to the primary publication.

^aBased on the assumption that the remainder of patients who had not previously received chemotherapy/monoclonal antibody and were not currently receiving treatment were treatment-naïve.

Abbreviations. BAI, Beck Anxiety Inventory; BDI-II, Beck Depression Inventory; BFI, Brief Fatigue Inventory; CES-D, Center for Epidemiologic Studies-Depression; CLL, chronic lymphocytic leukemia; ECOG, Eastern Cooperative Oncology Group; ECOG PS, Eastern Cooperative Oncology Group performance status; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30; EQ-5D-3L, EuroQol-5 Dimension Questionnaire – 3 Level; FACT-BMT, Functional Assessment of Cancer Therapy-Bone Marrow Transplant; FACT-G, Functional Assessment of Cancer Therapy-General; FACT-Leu, Functional Assessment of Cancer Therapy-Leukemia; FACT-Lym, Functional Assessment of Cancer Therapy-Lymphoma; HRQoL, health-related quality of life; NHS, National Health Service; NR, not reported; PROMIS, Patient-Reported Outcomes Measurement Information System; QoL, quality of life; SF-36, Short Form Health Survey-36; STAI, State-Trait Anxiety Index; UK, United Kingdom; USA, United States of America; VAS, visual analog scale.

Table 2. Instruments used to assess HRQoL in patients with CLL.

Instrument	Details of instrument
BAI	21-Item, validated self-report that has subjective, somatic, and panic subscales
BDI-II	21-Item, self-report measure for depression
BFI	Nine-question survey that measures the intensity, severity, and impact of fatigue
CES-D	20-Item measure to assess symptoms of depression
EORTC QLQ-C30	Comprises a functional scale, a global health scale, and a symptom scale assessing specific symptoms
EQ-5D	Generic measure of HRQoL with five dimensions – mobility, self-care, usual activities, pain/discomfort, anxiety/depression
FACT-G	Comprises four subscales and 27 items. The four domains are: physical wellbeing, social/family wellbeing, emotional wellbeing, and functional wellbeing
FACT-Leu	Measures cancer-specific and leukemia-specific HRQoL overall, in terms of physical, social, emotional, and functional wellbeing, and with respect to leukemia-specific considerations, including CLL
FACT-Lym	Assesses general concerns with cancer treatments plus specific concerns of patients with lymphoma
SF-36	36-item questionnaire generic measure of HRQoL
STAI	Psychologic inventory that quantifies anxiety with high scores indicating greater anxiety

Abbreviations. BAI, Beck Anxiety Inventory; BDI-II, Beck Depression Inventory; BFI, Brief Fatigue Inventory; CES-D, Center for Epidemiologic Studies Depression; CLL, chronic lymphocytic leukemia; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30; EQ-5D, EuroQol 5-dimension questionnaire; FACT-G, Functional Assessment of Cancer Therapy Questionnaire-General; FACT-Leu, Functional Assessment of Cancer Therapy-Leukemia; FACT-Lym, Functional Assessment of Cancer Therapy-Lymphoma; HRQoL, health-related quality of life; SF-36, Short-form 36; STAI, State-Trait Anxiety Index.

Figure 2. Flowchart of the economic burden review of CLL. ^aIncludes one study⁷ that analyzed data from a mixed population of patients with CLL with treatment failure. ^bIncludes one study⁴¹ that analyzed data from a mixed population of patients who had received ≥1 CLL-directed treatment. Abbreviations. CLL, chronic lymphocytic leukemia; SGA, subgroup available; SLR, systematic literature review.

Table 3. Overview of studies reporting cost and resource use data among first-line patients with CLL.

Study name	Publication type	Country	Sample size	Source of cost and resource use data	Perspective	Outcomes reported	Findings/conclusions
Delgado 2014^35	Conference abstract	Spain, Italy, UK	342	Retrospective chart review	NR	HRU	Hospitalization costs were the largest cost driver (3284 in Spain; 1312 in Italy; 10,291 in the UK)
Monberg 2014^40	Conference abstract	USA	2035	Truven Health Analytics MarketScan commercial and supplemental Medicare databases (January 2005–August 2012)	NR	Cost of specific AEs per course of first-line treatment	AE costs (frequency; adjusted cost): infusion reaction (40%; US$4482), anemia (35%; US$8894), infection (26%; US$7163), dyspnea (9%; US$859), neutropenia (8%; US$5406)
Gabriel 2016^33	Conference abstract	USA	1795	Truven Health MarketScan Research Database	NR	HCU	HCU of patients with CLL who remained on BR was significantly lower than patients who remained on FCR
Schenkel 2016^34	Conference abstract	USA	946	Large, national US claims database	NR	HRU	HRU (outpatient visits, ER visits and inpatient stays) varied by initial regimen received and was lower for rituximab compared with FCR and BR
Matasar 2017^32	Conference abstract	USA	707	US health insurance claims database	NR	Total healthcare costs	Ob ± chlorambucil had the lowest drug and total costs. Oral therapy with ibrutinib had the highest drug and OOP costs compared with those associated with a prescribed fixed number of cycles, and overall costs for ibrutinib were lower than FCR and BR
DaCosta 2018^39	Conference abstract	USA	707	US health insurance database	NR	HCU and costs	HCU was not significantly different across cohorts (BR, ibrutinib, FCR, Ob). Healthcare costs differed by initial regimen received and increased over time for ibrutinib
Nabhan 2017^38	Conference abstract	USA	1086	Registry payer and remittance dataset	NR	HRU and mean cost	When used in first cycle of therapy, rates of HRU and total costs of care for ibrutinib were significantly lower compared with chemotherapy/chemoimmunotherapy
Nabhan 2018^37	Conference abstract	USA	8008	Symphony Health’s Integrated Dataverse	NR	Total costs of medical care	Ibrutinib, when used first line, had lower HRU and ER visits than chemotherapy/chemoimmunotherapy
Wang 2018^36	Conference abstract	USA	1161	Optum Clinformatics Extended DataMart De-Identified Databases	NR	Pharmacy costs, medical costs, and HRU	Ibrutinib-treated patients incurred significantly higher pharmacy costs (mean monthly cost difference = US$6849; p<.0001), lower medical costs (US$10,615; p < .0001), resulting in a net cost reduction of US$3766 (p < .0001)
Wang 2018^7	Journal article	USA	2226 (n = 1025 with first-line TF)^a	Truven Health MarketScan Research Databases	Payers	TF costs; healthcare costs	Average TF cost was US$3011 PPPM (p< .001). Non-chemotherapy intervention (US$7582 PPPM; p < .0001) and FCR (US$4758 PPPM; p < .001) were associated with the highest TF cost

Shaded rows represent studies linked to the primary publication.

^aWang et al. line⁷ analyzed data from a mixed population of 2226 patients with CLL and TF; 1025 (46%) had first-line TF.

Abbreviations. AE, adverse event; BR, bendamustine and rituximab; CLL, chronic lymphocytic leukemia; ER, emergency room; FCR, fludarabine, cyclophosphamide, rituximab; HCU, healthcare utilization; HRU, healthcare resource utilization; NR, not reported; Ob, obinutuzumab; OOP, out-of-pocket; PPPM, per patient per month; TF, treatment failure; UK, United Kingdom; US, United States; USA, United States of America.

Table 4. Overview of studies reporting cost and resource use data among R/R patients with CLL.

Study	Publication type	Country	Sample size	Source of cost and resource use data	Perspective	Outcomes reported	Findings/conclusions
De Cock 2011^44	Conference abstract	France, Germany, Italy, Spain, UK	37	Medical charts	European perspective	HRU	High economic burden of patients with fludarabine-refractory CLL disease in Europe: average number of post-index ER visits was 0.8 and inpatient stays was 1.9; average inpatient stay was 11.2 days; 81% had multiple diagnostic investigations (average 11.5)
Parrondo Garcia 2014^45	Conference abstract	Spain	12	National databases, official government journals	Spanish National Health System	Healthcare costs (hospital stays, intervention)	Mean cost per patient was €46,613.32. Hospital stays and physician visits accounted for 47.74% of mean daily costs
Hassan 2014^43	Conference abstract	Canada	60	Cancer centers, Ontario	NR	Total costs, HRU	CLL treatments (CAN$11,248) and AEs (CAN$11,170) were major cost drivers. Per-patient costs were higher for male patients (CAN$24,926 vs. $CAN17,938), those with more advanced disease (Rai Stage IV, $CAN43,927), or those with p53 mutations ($CAN40,840)
Varker 2014^47	Conference abstract	USA	1109 (unfit and relapsed); 18,776 (unfit)	Truven Health MarketScan database	NR	Total costs	Rituximab regimens were the most commonly used in unfit/relapsed patients with CLL. Medical costs were substantial in this patient cohort (US$15,907 for first-line and US$18,506 for second-line therapies
Hassan 2017^42	Journal article	Canada	86	Federal, provincial schedules and wholesaler catalogs	NR	Overall costs; HRU	Mean costs per patient was CAN$25,736; 50% of the total cost was attributable to CLL treatment, among which fludarabine had the highest utilization
Reyes 2017^46	Conference abstract	USA	275	Medicare Limited Data Set 5% Standard Analytic Files (1999–2014)	NR	Cost by resource	During treatment, total all-cause healthcare costs were US$14,520 PPPM for BR and US$13,125 for bendamustine; outpatient costs represented the largest component
Nabhan 2018^48	Conference abstract	USA	385	Symphony Health’s Integrated Dataverse	NR	Total costs of medical care	The total cost of medical care was significantly higher in both the chemotherapy and chemoimmuntherapy groups compared with venetoclax (US$6076 and US$5515, respectively, vs. US$2440)
Kabadi 2019^41	Journal article	USA	7639 (n = 355 R/R patients)^a	Truven Health MarketScan research databases	NR	All-cause costs, CLL-related costs, HRU	BR was the most common first-line therapy for CLL (28.1%), with ibrutinib most preferred in the second (20.8%) and third line (25.5%). Ibrutinib was associated with higher per-patient costs than chemotherapy or chemoimmunotherapy (mean [SD] monthly per-patient cost, US$21,766 [US$36,140] for ibrutinib monotherapy, US$14,640 [US$12,925] for BR, US$12,742 [US$15,994] for FCR, and US$12,575 [US$18,072] for rituximab monotherapy. Mean monthly all-cause costs increased by the number of AEs; US$905 among those with no AEs to US$6032 among those with >6 AEs

^aKabadi et al. analyzed data from a mixed population of 7639 patients with CLL, which included 1379 who had received systemic (frontline) treatment; of treated patients, 355 (30%) received second- or subsequent line of therapy⁴¹.

Abbreviations. AE, adverse event; BR, bendamustine-rituximab; CAD, Canadian dollar; CLL, chronic lymphocytic leukemia; ER, emergency room; FCR, fludarabine, cyclophosphamide, rituximab; HRU, healthcare resource utilization; NR, not reported; PPPM, per patient per month; R/R, relapsed/refractory; UK, United Kingdom; US, United States; USA, United States of America.

Holzner B, Kemmler G, Sperner-Unterweger B, et al. Quality of life measurement in oncology-a matter of the assessment instrument? Eur J Cancer. 2001;37(18):2349–2356.

 PubMed Web of Science ®Google Scholar

Holzner B, Kemmler G, Kopp M, et al. Quality of life of patients with chronic lymphocytic leukemia: results of a longitudinal investigation over 1 yr. Eur J Haematol. 2004;72(6):381–389.

 PubMed Web of Science ®Google Scholar

Levin TT, Li Y, Riskind J, et al. Depression, anxiety and quality of life in a chronic lymphocytic leukemia cohort. Gen Hosp Psychiatry. 2007;29(3):251–256.

 PubMed Web of Science ®Google Scholar

Shanafelt TD, Bowen D, Venkat C, et al. Quality of life in chronic lymphocytic leukemia: an international survey of 1482 patients. Br J Haematol. 2007;139(2):255–264.

 PubMed Web of Science ®Google Scholar

Pashos CL, Flowers CR, Weiss M, et al. Variation in health-related quality of life by age among patients with chronic lymphocytic leukemia. Value Health. 2012;15(4):A226.

 Web of Science ®Google Scholar

Pashos CL, Flowers CR, Weiss M, et al. Variation in health-related quality of life by ECOG performance status and fatigue among patients with chronic lymphocytic leukemia. Blood. 2011;118(21):4591.

 PubMed Web of Science ®Google Scholar

Kay NE, Flowers C, Weiss M, et al. Variation in health-related quality of life by line of therapy of patients with chronic lymphocytic leukemia. Blood. 2012;120(21):3926.

 Google Scholar

Pashos CL, Flowers CR, Kay NE, et al. Association of health-related quality of life with gender in patients with B-cell chronic lymphocytic leukemia. Support Care Cancer. 2013;21(10):2853–2860.

 PubMed Web of Science ®Google Scholar

Pashos CL, Flowers CR, Weiss M, et al. Association of health-related quality of life with gender in patients with B-cell chronic lymphocytic leukemia. Support Care Cancer. 2012;20:S242.

 Google Scholar

McCarrier KP, Bull S, Simacek KF, et al. Online social networks-based qualitative research to identify patient-relevant concepts in chronic lymphocytic leukemia. Value Health. 2014;17(3):A196.

 PubMed Web of Science ®Google Scholar

Mudondo NP, Parry HM, Damery S, et al. Psychological wellbeing amongst early stage chronic lymphocytic leukaemia patients: a comparative study of primary versus secondary care follow up. Br J Haematol. 2014;165:58.

 Web of Science ®Google Scholar

Hahn M, Dietrich S, Hegenbart U, et al. Quality of life (QoL) assessment in patients allografted for poor-risk chronic lymphocytic leukemia (CLL). Bone Marrow Transplant. 2015;50:S422.

 Web of Science ®Google Scholar

Holtzer-Goor KM, Schaafsma MR, Joosten P, et al. Quality of life of patients with chronic lymphocytic leukaemia in the Netherlands: results of a longitudinal multicentre study. Qual Life Res. 2015;24(12):2895–2906.

 PubMed Web of Science ®Google Scholar

Buzaglo JS, Miller MF, Karten C, et al. Distress and perceived impact on well-being for low- or intermediate-risk and high-risk patients with chronic lymphocytic leukemia (CLL). Blood. 2016;128(22):5970.

 Web of Science ®Google Scholar

Buzaglo JS, Miller MF, Zaleta AK, et al. Chronic lymphocytic leukemia patient reported outcomes and quality of life: findings from the cancer experience registry. Blood. 2017;130:2122.

 Google Scholar

Williams A, Yarosh R, Clark J, et al. Correlates of anxiety and depression in chronic lymphocytic leukemia (CLL) survivors. J Clin Oncol. 2018;36(7_suppl):153.

 Web of Science ®Google Scholar

Yu H, Zhang H, Yang J, et al. Health utility scores of family caregivers for leukemia patients measured by EQ-5D-3L: a cross-sectional survey in China. BMC Cancer. 2018;18(1):950.

 PubMed Web of Science ®Google Scholar

Wang S, Lafeuille MH, Lefebvre P, et al. Economic burden of treatment failure in chronic lymphocytic leukemia patients. Curr Med Res Opin. 2018;34(6):1135–1142.

 PubMed Web of Science ®Google Scholar

Kabadi SM, Near A, Wada K, et al. Treatment patterns, adverse events, and economic burden in a privately insured population of patients with chronic lymphocytic leukemia in the United States. Cancer Med. 2019;8(17):7174–7110.

 PubMed Web of Science ®Google Scholar

Delgado J, Rossi D, Forconi F, et al. Characterising the burden of chronic lymphocytic leukemia in fludarabine-ineligible patients in Spain, Italy, and the United Kingdom (UK): a retrospective observational study. Blood. 2014;124(21):2646.

 Web of Science ®Google Scholar

Monberg MJ, Shukla A, Le HV, et al. Economic cost of adverse events per course of therapy with commonly used first-line regimens for the treatment of chronic lymphocytic leukemia. Value Health. 2014;17(3):A79.

 Web of Science ®Google Scholar

Gabriel S, Szabo E, Lo-Coco F, et al. Differences in healthcare utilization in CLL patients treated with BR versus FCR. Blood. 2016;128(22):2406.

 Google Scholar

Schenkel B, Ellis L, Korrer S, et al. Real-world treatment patterns and health care resource utilization (HRU) among patients with chronic lymphocytic leukemia (CLL) by regimen. J Clin Oncol. 2016;34(7_suppl):15.

 Web of Science ®Google Scholar

Matasar MJ, DaCosta Byfield S, Blauer-Peterson C, et al. What are the health care costs for chronic lymphocytic leukemia? J Clin Oncol. 2017;35(8_suppl):15.

 Web of Science ®Google Scholar

DaCosta BS, Blauer-Peterson C, Dawson K, et al. What are the health care utilization and costs associated with patients newly initiating anti-cancer systemic therapy for chronic lymphocytic leukemia?. J Managed Care Spec Pharm. 2018;24:S29.

 PubMed Web of Science ®Google Scholar

Nabhan C, Mato AR, Kish JK, et al. Comparison of costs and health care resource utilization (HRU) in chronic lymphocytic leukemia (CLL) patients treated with front-line ibrutinib or chemoimmunotherapy. Blood. 2017;130(Supplement 1):2111.

 PubMed Web of Science ®Google Scholar

Nabhan C, Nero D, Hyung Lee C, et al. Cost-effectiveness comparison between ibrutinib, chemotherapy, and chemoimmunotherapy in front-line treatment of chronic lymphocytic leukemia (CLL). Blood. 2018;132(Supplement 1):4757.

 Web of Science ®Google Scholar

Wang S, Emond B, Romdhani H, et al. Front-line ibrutinib treatment is associated with longer time to next treatment, net total cost reduction, and lower healthcare resource utilization compared to chemoimmunotherapy in patients with chronic lymphocytic leukemia. Blood. 2018;132(Supplement 1):2306.

 Web of Science ®Google Scholar

De Cock E, Haiderali A, Wasiak R, et al. The natural history of fludarabine-refractory chronic lymphocytic leukemia patients who fail alemtuzumab or have bulky lymphadenopathy – a European perspective. Value Health. 2011;14(7):A456.

 Web of Science ®Google Scholar

Parrondo Garcia J, Loscertales Pueyo J, Roldán Acevedo C, et al. Burden of illness of patients with chronic lymphocytic leukemia that are refractory to fludarabine and alemtuzumab-containing regimens in Spain: Average cost estimation by Monte Carlo simulation. Haematologica. 2014;99:218.

 Web of Science ®Google Scholar

Hassan S, Seung SJ, Bannon G, et al. Health care resource utilization in the management of chronic lymphocytic leukemia in two cancer centres in Ontario. Value Health. 2014;17(3):A79.

 Web of Science ®Google Scholar

Varker H, Meyer N, Gregory S, et al. Treatment patterns, mortality, and costs of care in unfit patients (pts) with relapsed chronic lymphocytic leukemia (CLL). J Clin Oncol. 2014;32(15_suppl):7105.

 Web of Science ®Google Scholar

Hassan S, Seung SJ, Cheung MC, et al. Examining the medical resource utilization and costs of relapsed and refractory chronic lymphocytic leukemia in Ontario. Curr Oncol. 2017;24(1):e50–e54.

 PubMed Web of Science ®Google Scholar

Reyes C, Gauthier G, Schmerol L, et al. Healthcare cost of Medicare patients with previously treated chronic lymphocytic leukemia. Haematologica. 2017;102:717.

 Web of Science ®Google Scholar

Nabhan C, Mato AR, Kish JK, et al. Comparison of costs and health care resource utilization (HRU) in chronic lymphocytic leukemia (CLL) patients treated with venetoclax (VEN) or chemotherapy (CT)/chemoimmunotherapy (CIT). Blood. 2018;132(Supplement 1):4758.

 Web of Science ®Google Scholar