Systematic Literature Review of the Indirect Costs, Humanistic Burden, Patient or Caregiver Preference, and Qualitative Outcomes in Beta-Thalassemia

Abstract Introduction: Beta-thalassemia is a hereditary blood disorder with some patients requiring frequent blood transfusions. Lifelong management of the disease and its complications imposes a severe burden on patients. This study aimed to understand the indirect costs and humanistic burden, treatment preferences, and perceptions of treatment and outcomes in patients with beta-thalassemia. Methods: Systematic literature searches were conducted in Embase, MEDLINE, and MEDLINE In-Process to identify articles on patients with beta-thalassemia published between November 2010 and 2020. Studies were included if they reported on patients with beta-thalassemia of any age regarding indirect costs, health-related quality of life (HRQoL), patient/caregiver preference, and qualitative outcomes in observational, economic, and preference elicitation studies. Search methods followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane. Results: Searches yielded 2387 records; 95 publications were included (Figure). The mean annual costs due to productivity losses in patients with transfusion-dependent beta-thalassemia (TDT) was 24% of all treatment costs. The cost of lost welfare due to pain and suffering in TDT in Iran in 2015 was USD 1360.50 per year per patient. Lost opportunities for TDT patients in Iran were highest in the age group 31-40 years and lowest in the age group 0-10 years. Lost opportunities for patients' families were highest in the age group 11-20 years. The mean annual transportation cost for TDT patients in Iran for visits to hospitals was EUR 132.77 (standard deviation [SD] 15.50). The indirect burden of absenteeism due to transfusion ranged from 13.5 to 30 days in patients and 19 days in caregivers, annually. Mean indirect burden due to disease management in TDT patients was 592 min (SD 349) on transfusion days (for activities including undergoing transfusion, cross-matching of blood, arranging childcare, arranging insurance payments) and 91 min (SD 221) on non-transfusion days. No studies on indirect costs were identified in the non-transfusion dependent beta-thalassemia (NTDT) population. Blood transfusion is used to reduce pain and fatigue in TDT patients and scores for fatigue and pain were worse for a period of 5 days before transfusion (mean Brief Fatigue Inventory score 5.05 vs 4.29; mean Brief Pain Inventory-Short Forms score 4.33 vs 3.85). HRQoL outcomes were reported to be associated with age (better HRQoL in ≤14 years of age, P=0.015, P=0.008), sex (better HRQoL in males, P=0.035, P=0.041, P=0.009), lower serum ferritin (better HRQoL, P=0.05, P=0.004), compliance to iron chelation therapies (better HRQoL, P<0.01, P=0.004), heart failure (worse HRQoL, P<0.001), higher income (better HRQoL, P<0.001), being employed (better HRQoL, P=0.01), higher education (better HRQoL, P<0.001). Patients with TDT and NTDT reported worse HRQoL scores on SF-36 general health domain than the general population (mean [SD] 44.1 [9.3] vs 50 [10]). Long-term HRQoL in patients who underwent hematopoietic stem cell transplantation 20 years ago was comparable to the general population (SF-36 change in HRQoL −8.9; 95% CI, −15.0 to 2.7, P=0.005). Studies indicated a high prevalence of depression in TDT patients; >50% of TDT patients suffered from mild to severe stress, anxiety, and depression. In TDT children, mental health was the most affected domain of SF-36 compared to healthy peers (48.6 vs 96.6, P<0.001). NTDT patients were reported to have lower scores on all domains of the FACT scale than TDT patients indicating worse HRQoL (−4.8 vs −4.7, P=0.009). Patient preference and qualitative studies were conducted in low- and middle-income countries and findings mostly corresponded to results from HRQoL studies. Patients/caregivers frequently reported feelings of uncertainty, anxiety, depression, and thoughts of dying. Social stigma substantially affected the lives of those affected by beta-thalassemia and contributed to adverse financial impacts. Conclusions: TDT is associated with high indirect costs, including productivity losses, absenteeism, transportation cost, and societal losses. Further research is needed to understand the indirect cost burden on NTDT patients. The findings highlight the unmet need for novel therapies, and optimal disease management approaches to decrease the economic burden of TDT in patients and their caregivers. Figure 1 Figure 1. Disclosures Aydinok: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Resonance Health: Research Funding; CRISPR Therapeutics: Consultancy; SLN Therapeutics: Consultancy; Imara: Research Funding; Protagonist: Membership on an entity's Board of Directors or advisory committees, Research Funding; LaJolla: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ionis Pharmaceuticals: Research Funding. Purushotham: Evidera: Consultancy, Current Employment. Yucel: BMS: Current Employment, Current holder of individual stocks in a privately-held company. Deshpande: Evidera Ltd: Consultancy, Current Employment. Potrata: Evidera Ltd: Current Employment. Trapali: Evidera Ltd: Consultancy, Current Employment. Dixit: Evidera: Current Employment. Shah: Bristol Myers Squibb: Honoraria.

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Treatment Patterns and Outcomes in Elderly Patients with Newly Diagnosed Multiple Myeloma: Results from the Connect® MM Registry

Blood ◽

10.1182/blood-2019-126205 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3129-3129

Author(s):

Hans C. Lee ◽

Sikander Ailawadhi ◽

Cristina Gasparetto ◽

Sundar Jagannath ◽

Robert M. Rifkin ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Causes Of Death ◽

Age Groups ◽

Treatment Patterns ◽

Age Group ◽

Newly Diagnosed ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership

Background: Multiple myeloma (MM) is common among the elderly, with 35% of patients (pts) diagnosed being aged ≥75 years (y). With increasing overall life expectancy, the incidence and prevalence of newly diagnosed and previously treated MM patients ≥80 y is expected to increase over time. Because elderly pts are often excluded from clinical trials, data focused on their treatment patterns and clinical outcomes are lacking. The Connect® MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed MM (NDMM) designed to examine real-world diagnostic patterns, treatment patterns, clinical outcomes, and health-related quality of life patient-reported outcomes. This analysis reviews treatment patterns and outcomes in elderly pts from the Connect MM Registry. Methods: Pts enrolled in the Connect MM registry at 250 community, academic, and government sites were included in this analysis. Eligible pts were adults aged ≥18 y with symptomatic MM diagnosed ≤2 months before enrollment, as defined by International Myeloma Working Group criteria; no exclusion criteria were applied. For this analysis, pts were categorized into 4 age groups: <65, 65 to 74, 75 to 84, and ≥85 y. Pts were followed from time of enrollment to the earliest of disease progression (or death), loss to follow-up, or data cutoff date of February 7, 2019. Descriptive statistics were used for baseline characteristics and treatment regimens. Survival outcomes were analyzed using Cox regression. Time to progression (TTP) analysis excluded causes of death not related to MM. Results: Of 3011 pts enrolled (median age 67 y), 132 (4%) were aged ≥85 y, and 615 (20%) were aged 75-84 y at baseline. More pts aged ≥85 y had poor prognostic factors such as ISS stage III disease and reduced hemoglobin (<10 g/dL or >2 g/dL <LLN) compared with other age groups, although no notable differences between creatinine and calcium levels were observed across age groups (Table). A lower proportion of elderly pts (75-84 and ≥85 y) received triplet regimens as frontline therapy. More elderly pts received a single novel agent, whereas use of 2 novel agents was more common in younger pts (Table). The most common frontline regimens among elderly pts were bortezomib (V) + dexamethasone (D), followed by lenalidomide (R) + D, whereas those among younger pts included RVD, followed by VD and CyBorD (Table). No pt aged ≥85 y, and 4% of pts aged 75-84 y received high-dose chemotherapy and autologous stem cell transplant (vs 61% in the <65 y and 37% in the 65-74 y age group). The most common maintenance therapy was RD in pts ≥85 y (although the use was low) and R alone in other age groups (Table). In the ≥85 y group, 27%, 10%, and 4% of pts entered 2L, 3L, and 4L treatments respectively, vs 43%, 23%, and 13% in the <65 y group. Progression-free survival was significantly shorter in the ≥85 y age group vs the 75-84 y age group (P=0.003), 65-74 y age group (P<0.001), and <65 y age group (P<0.001; Fig.1). TTP was significantly shorter in the ≥85 y group vs the <65 y group (P=0.020); however, TTP was similar among the 65-74 y, 75-84 y, and ≥85 y cohorts (Fig. 2). Overall survival was significantly shorter in the ≥85 y group vs the 75-84 y, 65-74 y, and <65 y groups (all P<0.001; Fig. 3). The mortality rate was lowest (46%) during first-line treatment (1L) in pts aged ≥85 y (mainly attributed to MM progression) and increased in 2L and 3L (47% and 54%, respectively); a similar trend was observed in the younger age groups. The main cause of death was MM progression (29% in the ≥85 y vs 16% in the <65 y group). Other notable causes of death in the ≥85 y group included cardiac failure (5% vs 2% in <65 y group) and pneumonia (5% vs 1% in <65 y group). Conclusions: In this analysis, elderly pts received similar types of frontline and maintenance regimens as younger pts, although proportions varied with decreased use of triplet regimens with age. Considering similarities in TTP across the 65-74 y, 75-84 y, and ≥85 y cohorts, these real-world data support active treatment and aggressive supportive care of elderly symptomatic pts, including with novel agents. Additionally, further clinical studies specific to elderly patients with MM should be explored. Disclosures Lee: Amgen: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ailawadhi:Janssen: Consultancy, Research Funding; Takeda: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Cellectar: Research Funding. Gasparetto:Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Jagannath:AbbVie: Consultancy; Merck & Co.: Consultancy; Bristol-Myers Squibb: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy. Rifkin:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Narang:Celgene: Speakers Bureau. Terebelo:Celgene: Honoraria; Jannsen: Speakers Bureau; Newland Medical Asociates: Employment. Toomey:Celgene: Consultancy. Hardin:Celgene: Membership on an entity's Board of Directors or advisory committees. Wagner:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Cancer Society: Other: Section editor, Cancer journal. Omel:Celgene, Takeda, Janssen: Other: Patient Advisory Committees. Srinivasan:Celgene: Employment, Equity Ownership. Liu:TechData: Consultancy. Dhalla:Celgene: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Abonour:BMS: Consultancy; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

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Variation in Health-Related Quality of Life by Age Among Patients with Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v118.21.2085.2085 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2085-2085

Author(s):

Chris L. Pashos ◽

Christopher R Flowers ◽

Mark Weiss ◽

Nicole Lamanna ◽

Charles M Farber ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Age Groups ◽

Lymphocytic Leukemia ◽

Age Group ◽

Employment Equity ◽

Advisory Committees ◽

Related Quality ◽

Health Related ◽

Equity Ownership

Abstract Abstract 2085 Introduction. Although advanced patient age is commonly used as a factor in selecting therapy for patients with chronic lymphocytic leukemia (CLL), based on presumed associations with functional status, limited data exist regarding the relationships between age and physical, emotional, social, and functional well being. We examined the relationships between age and these domains of health-related quality of life (HRQOL) for CLL patients treated in US community practices. Methods. Baseline data were collected as part of Connect CLL®, a prospective observational registry initiated in March 2010 involving centers in the US. Data on patient demographics and clinical characteristics were provided by clinicians. HRQOL was self-reported by patients in the clinic at enrollment. Patients completed 3 psychometrically validated instruments: the Brief Fatigue Inventory (BFI), EQ-5D, and Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu). Standard analyses were conducted of each instrument given clinical characteristics at that time. Reported mean BFI, EQ-5D and FACT-Leu scores were analyzed by age group (<65, 65–74, >74). Statistical significance of score differences among sub-cohorts was ascertained by ANOVA using SAS 9.1. Results. Baseline HRQOL data were reported by 604 patients, enrolled from 161 centers. Patients were predominantly male (62%) and white (90%) with mean age at 69.9 (standard deviation [SD] 11.2) yrs. HRQOL scores by age group are presented: There were no significant differences between the age groups in fatigue as measured by the BFI, or differences in overall HRQOL as measured by the EQ-5D Visual Analogue Scale (VAS) or the FACT-G. Anxiety/depression and self care are EQ-5D domains that also did not vary by age. Although mobility was most impaired in the oldest age group compared to the two younger groups, usual activities and pain/discomfort were worse in both the younger and older cohorts compared to those 65–74 years of age. FACT-Leu results indicated that the social/family domain scores did not vary by age, but that physical, emotional, and functional domains did vary statistically with the oldest typically doing better than the 65–74 year olds, but not necessarily better than those <65. Conclusions. Initial results from the Connect CLL® Registry indicate that HRQOL does not worsen monotonically with older age. In this cohort, both the youngest and oldest age groups had worse HRQOL in certain domains, presenting an inverted v-shaped relationship. Future analyses should be conducted on: (1) how HRQOL may be affected over time with changes in disease; and, (2) how HRQOL may be influenced by alternative therapies. Results reported here should serve as a useful baseline reference. Disclosures: Pashos: Celgene: Membership on an entity's Board of Directors or advisory committees. Flowers:Genentech/Roche (unpaid): Consultancy; Celgene: Consultancy; Millennium/Takeda: Research Funding; Wyeth: Research Funding; Novartis: Research Funding. Weiss:Celgene: Membership on an entity's Board of Directors or advisory committees. Lamanna:Celgene: Membership on an entity's Board of Directors or advisory committees. Farber:Celgene: Membership on an entity's Board of Directors or advisory committees. Kipps:Igenica: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Abbot Industries: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; GSK: Research Funding; Gilead Sciences: Consultancy, Research Funding; Amgen: Research Funding. Lerner:Celgene: Membership on an entity's Board of Directors or advisory committees. Kay:Celgene: Membership on an entity's Board of Directors or advisory committees. Sharman:Celgene: Membership on an entity's Board of Directors or advisory committees. Grinblatt:Celgene: Membership on an entity's Board of Directors or advisory committees. Flinn:Celgene: Membership on an entity's Board of Directors or advisory committees. Kozloff:Celgene: Membership on an entity's Board of Directors or advisory committees. Swern:Celgene Corporation: Employment, Equity Ownership. Kahn:Celgene Corporation: Employment, Equity Ownership. Street:Celgene: Employment, Equity Ownership. Sullivan:Celgene: Employment, Equity Ownership. Keating:Celgene: Membership on an entity's Board of Directors or advisory committees.

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Quality of Life and Caregiver Burden in Patients and Their Caregivers Undergoing Outpatient Autologous Stem Cell Transplantation Compared to Inpatient Transplantation

Blood ◽

10.1182/blood-2019-131281 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 62-62

Author(s):

Vinita Dhir ◽

Lara Zibdawi ◽

Harminder K Paul ◽

Osvaldo Espin-Garcia ◽

Christine I Chen ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

Indirect Costs ◽

Opportunity Costs ◽

Advisory Committees ◽

Significant Difference ◽

Lost Opportunity ◽

Out Of Pocket Costs

Introduction Outpatient autologous stem cell transplantation (ASCT) has become standard of care in many centres due to limited inpatient resources and rising financial constraints. Outpatient ASCT involves family members/friends assuming some patient care responsibilities during the acute transplant period. Although this may be associated with reduced direct medical costs, little work has been done to ascertain the "out of pocket costs" and "lost opportunity costs" to patients and their caregivers. Outpatient transplantation is perceived to provide superior quality of life (QOL) for patients, but there is little evidence to support this. In addition to patients' QOL, there is limited data on the impact of these treatments on caregivers' QOL. Thus, our objectives were to compare the QOL of patients and their caregivers undergoing outpatient and inpatient ASCT, and to quantify indirect costs to them. Methods This is a single centre cohort study of consecutive patients with lymphoma and plasma cell disorders undergoing ASCT at Princess Margaret Cancer Centre from April 2016 - July 2019. Patients without a primary caregiver were still eligible to complete the QOL portion of the study. All patients completed four questionnaires: Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT); FACT-Fatigue (FACT-F); EQ-5D-3L; and a distress impact thermometer. Clinically meaningful differences between the groups and serially were defined as ≥ 4 points on the FACT-BMT and FACT-F, and ≥0.08 on the EQ-5D-3L. Caregivers completed three questionnaires: Caregiver Quality of Life Index-Care (C-QOLC), a distress impact thermometer, and a caregiver self-administered financial expenditure survey (C-SAFE). Indirect costs were defined as lost opportunity costs (i.e., wages) and out-of-pocket costs (e.g., parking, accommodations). Questionnaires were completed at 5 time points: D0 (prior to ASCT), D+7, D+14 (discharge from daily visits), D+28 (discharge from ASCT) and D+100 (follow-up). Results In total, 68 patients have been enrolled to date (41 outpatients and 27 inpatients), and 54 caregivers (38 outpatients and 16 inpatients). Median patient age was 57 yrs (range: 18-71), and 66% were male. Of the 68 patients, 69% had a diagnosis of multiple myeloma and 31% lymphoma. Majority of caregivers were spouses (74%). In the overall sample, FACT-F scores (fatigue) increased significantly at D+7, D+14, and D+28, with improvement at D+100 (all p<0.05 and clinically meaningful). Compared to inpatients, outpatients had higher fatigue levels at D+7 and D+14 that were statistically significant (Figure 1), with D+14 being clinically significant as well. For all patients, QOL scores by FACT-BMT declined at D+7, but then improved to above baseline values at D+100 (p<0.05) (Table 1). On the EQ-5D-3L, patients' self-reported overall best imaginable health status decreased at D+7 and D+14 relative to baseline (p<0.05); no significant difference was observed at D+28 and D+100 (Figure 1). Health utility scores were also calculated from the EQ-5D-3L. There were no significant trends in the overall sample, but when comparing the two groups, outpatients had lower measures at D+14 that were statistically and clinically relevant. With respect to caregiver QOL, in the entire sample, QOL was higher at D+100 relative to baseline (p<0.05) (Figure 2). There were no differences between the two groups. In addition, there was no statistically significant difference in lost opportunity costs (wages) between the two groups, however there was a trend towards higher lost opportunity costs in outpatient caregivers in the early ASCT process (D0, D+7, D+14). The mean overall costs (burden) for the primary caregiver in the acute first 100d phase of ASCT was C$4475. The indirect out-of-pocket costs by caregivers varied greatly, with an average of $58 at baseline (range $0-455) and $121 at D+28 (range $0-710). Conclusions There was significant deterioration of various QOL measures in all patients, irrespective of outpatient or inpatient status. Outpatients, however, reported significantly higher fatigue levels at D+7 and D+14. Caregiver QOL appears comparable between the two modalities, and appears to improve significantly by the follow-up period. The financial burden on caregivers, mostly driven by lost opportunity costs (wages), is high, with a trend towards higher burden in outpatient caregivers in the early parts of ASCT. Disclosures Chen: Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria. Kridel:Gilead Sciences: Research Funding. Kukreti:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Kuruvilla:Celgene: Honoraria; Astra Zeneca: Honoraria; Seattle Genetics: Consultancy; Amgen: Honoraria; Roche: Consultancy; Karyopharm: Consultancy; Gilead: Consultancy; Abbvie: Consultancy; BMS: Consultancy; Roche: Research Funding; Janssen: Research Funding; Merck: Consultancy; Gilead: Honoraria; BMS: Honoraria; Karyopharm: Honoraria; Janssen: Honoraria; Roche: Honoraria; Seattle Genetics: Honoraria; Novartis: Honoraria; Merck: Honoraria. Reece:Otsuka: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Research Funding. Tiedemann:Amgen: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Celgene: Honoraria; BMS: Honoraria; Janssen: Honoraria. Trudel:Pfizer: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria; Janssen: Honoraria, Research Funding; Astellas: Research Funding; Genentech: Research Funding; Sanofi: Honoraria. Prica:Janssen: Honoraria; Celgene: Honoraria.

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Health-Related Quality of Life Outcomes for Patients with Transfusion-Dependent Beta-Thalassemia Treated with Luspatercept in the Believe Trial

Blood ◽

10.1182/blood-2020-136312 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 8-9

Author(s):

Maria Domenica Cappellini ◽

Ali T. Taher ◽

Antonio Piga ◽

Farrukh Shah ◽

Ersi Voskaridou ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

Publicly Traded ◽

Advisory Committees ◽

Meaningful Improvement ◽

Sf 36 ◽

La Jolla ◽

Domain Scores

Introduction: Patients (pts) with transfusion-dependent (TD) β-thalassemia may require long-term red blood cell transfusions (RBCT) that can lead to iron overload and associated complications, which impact negatively on health-related quality of life (HRQoL). Administration of RBCT provides transient relief from anemia-related symptoms associated with β-thalassemia; reduction of RBCT may increase anemia-related symptoms and thereby worsen HRQoL. The phase 3 BELIEVE study (NCT02604433) showed that the first-in-class erythroid maturation agent luspatercept provided clinically meaningful reduction in RBCT burden, but the impact of luspatercept on HRQoL is not well understood. This analysis assessed the effect of luspatercept plus best supportive care (BSC, including RBCT, iron chelation therapy) vs placebo (PBO) plus BSC on HRQoL in pts with TD β-thalassemia. Methods: Pts received luspatercept (starting dose 1.0 mg/kg with titration up to 1.25 mg/kg every 3 weeks) or PBO, subcutaneously for ≥ 48 weeks plus BSC. HRQoL was assessed using the generic 36-item Short Form Health Survey (SF-36) and the thalassemia-specific Transfusion-dependent Quality of Life questionnaire (TranQol), at screening (≤ 4 weeks prior to first study dose) and every 12 weeks up to 48 weeks of treatment. The HRQoL evaluable population included all pts who completed the HRQoL assessment at screening and ≥ 1 post-screening assessment visit. The TranQol and SF-36 were considered complete if ≥ 75% and ≥ 50% of items, respectively, were answered at a given time point. The primary analysis assessed changes from baseline between groups up to Week 48. The primary domains of interest were: TranQol total score and Physical Health (PH); and the SF-36 Physical Component Summary (PCS), Physical Functioning (PF), and General Health (GH). Other domains were considered exploratory domains. Changes from baseline were compared using ANCOVA models adjusting for baseline domain scores and geographic region. In exploratory analyses, the proportion of pts achieving a clinically meaningful improvement in domain scores were compared between pts on luspatercept achieving a clinical response (≥ 50% reduction in RBCT burden over 12 weeks; ≥ 33% reduction in RBCT burden over 12 weeks; transfusion independence [TI] any 8 weeks; or TI any 12 weeks), and PBO. Results: 336 pts were randomized to treatment; 224 to luspatercept and 112 to PBO. The HRQoL evaluable population was 212 (94.6%) in the luspatercept arm and 104 (92.9%) in the PBO arm. HRQoL questionnaire compliance rates among pts still on treatment were > 87.5% for both questionnaires at Week 48. Baseline HRQoL scores were similar to the US general population for most SF-36 domains, although GH, Role-Emotional, and Role-Physical domain scores were impaired in the BELIEVE population. Mean scores on all primary and exploratory domains were stable over time in both treatment groups and did not differ between treatment groups at Week 24 and 48. When considering responders to luspatercept, pts receiving luspatercept and achieving a ≥ 50% reduction in RBCT burden over 12 weeks were significantly more likely than pts receiving PBO to have a clinically meaningful improvement in PCS (31.1% vs 16.5%; P = 0.024), and PF (30.0% vs 13.2%; P = 0.007) at Week 48 (Table). Statistically significant differences between luspatercept and PBO were also seen among pts achieving TI for any 8 or any 12 weeks for some SF-36 domains, but no statistical difference was seen in pts achieving a ≥ 33% reduction in RBCT burden for either SF-36 or TranQol domains although the proportion of pts with improved scores was higher with luspatercept, especially at Week 48. Conclusions: Overall, the addition of luspatercept to BSC reduced transfusion burden while sustaining TranQol and SF-36 HRQoL scores over time through Week 48 compared with those receiving PBO. Pts with TD β-thalassemia responding to luspatercept were more likely to achieve clinically meaningful improvements in HRQoL compared with PBO. Disclosures Cappellini: Genzyme/Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics, Novartis, Vifor Pharma: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria. Taher:Silence Therapeutics: Consultancy; Vifor Pharma: Consultancy, Research Funding; Ionis Pharmaceuticals: Consultancy; BMS: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding. Piga:BMS: Research Funding; Novartis: Research Funding. Shah:Novartis, BMS: Consultancy, Honoraria, Speakers Bureau; Bluebird Bio: Consultancy, Honoraria; IQVIA: Consultancy, Membership on an entity's Board of Directors or advisory committees. Voskaridou:ADDMEDICA Company: Consultancy, Research Funding; BMS: Consultancy, Research Funding; ACCELERON Company: Consultancy, Research Funding; PROTAGONIST Company: Research Funding; GENESIS Company: Consultancy, Research Funding; NOVARTIS Company: Research Funding. Viprakasit:Agios Pharmaceuticals, Ionis Pharmaceuticals, La Jolla Pharmaceuticals, Protagonist Therapeutics, Vifor Pharma: Consultancy, Research Funding; BMS, Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Porter:Silence Therapeutics: Honoraria; La Jolla Pharmaceuticals: Honoraria; Vifor Pharmaceuticals: Honoraria; Protagonist Therapeutics: Honoraria; BMS: Consultancy, Honoraria; Agios Pharmaceuticals: Consultancy, Honoraria; bluebird bio, Inc.: Consultancy, Honoraria. Hermine:AB Science: Consultancy, Current equity holder in publicly-traded company, Honoraria, Patents & Royalties, Research Funding; BMS, Alexion, Novartis, Inatherys: Research Funding. Neufeld:Takeda: Consultancy; Octapharma: Consultancy; Novo Nordsik: Consultancy; genetech: Consultancy; Bayer: Other: DSMB; Imara Pharma: Other: DSMB service; ApoPharma/Chiezi: Other: DSMB service; Pfizer: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Acceleron Pharma: Consultancy, Other: DSMB. Thompson:BMS: Consultancy, Research Funding; Baxalta: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; CRISPR/Vertex: Research Funding; bluebird bio, Inc.: Consultancy, Research Funding; Biomarin: Research Funding. Tang:BMS: Current Employment, Current equity holder in publicly-traded company. Yu:Evidera: Current Employment. Guo:BMS: Consultancy. Shetty:BMS: Current Employment, Current equity holder in publicly-traded company. Miteva:BMS: Current Employment. Zinger:Celgene, a Bristol Myers Squibb company: Current Employment. Backstrom:Acceleron Pharma: Current Employment, Current equity holder in publicly-traded company; BMS: Current equity holder in publicly-traded company. Oliva:Abbvie: Consultancy; Amgen: Consultancy; Novartis: Consultancy; BMS: Consultancy, Honoraria, Patents & Royalties, Speakers Bureau; Alexion: Consultancy; Apellis: Consultancy.

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Quality of Life and Caregiver Burden in Patients and Their Caregivers Undergoing Outpatient Autologous Stem Cell Transplantation Compared to Inpatient Transplantation

Blood ◽

10.1182/blood-2021-153120 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3055-3055

Author(s):

Anca Prica ◽

Vinita Dhir ◽

Rachel Aitken ◽

Harminder K Paul ◽

Osvaldo Espin-Garcia ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

Indirect Costs ◽

Well Being ◽

Advisory Committees ◽

Caregiver Quality ◽

Lost Opportunity ◽

Out Of Pocket Costs

Abstract Introduction Outpatient autologous stem cell transplantation (ASCT) has become standard of care in many centres due to limited inpatient resources and rising financial constraints. Outpatient ASCT involves family members/friends assuming patient care responsibilities during the acute transplant period. Although this may be associated with reduced direct medical costs, less is known about the "out of pocket costs" and "lost opportunity costs" to patients and their caregivers, as well as impact on caregiver quality of life (QOL). Outpatient transplantation is perceived to provide superior QOL for patients, but there is little evidence to support this. Thus, our objectives were to compare the QOL of patients and their caregivers undergoing outpatient and inpatient ASCT, and to quantify indirect costs to them. Methods This is a single centre cohort study of patients with lymphoma and multiple myeloma undergoing ASCT at Princess Margaret Cancer Centre from April 2016 - February 2021. Patients without a primary caregiver were still eligible to complete the QOL portion of the study. Patients completed several questionnaires including FACT-BMT, FACT-F, and EQ-5D. Caregiver questionnaires included: Caregiver Quality of Life Index-Care (C-QOLC), and a caregiver self-administered financial expenditure survey (C-SAFE). Total indirect costs were defined as lost opportunity costs (i.e., wages) plus out-of-pocket costs (e.g., parking, accommodations). Questionnaires were completed at 5 time points: D0 (prior to ASCT), D+7, D+14 (discharge from daily visits), D+28 (discharge from ASCT) and D+100 (follow-up). Demographic and clinical characteristics were assessed using descriptive statistics. Pairwise changes in QOL from baseline were assessed using linear mixed models to account for repeated measures with group, age and sex included as fixed effects. Alpha was defined as p<0.05. Results A total of 97 patients (49 outpatients and 45 inpatients) and 66 caregivers (43 outpatients and 22 inpatients) were enrolled. Patients had a median age of 59 years (range 18-71) and were predominantly male (60%) with 66% diagnosed with multiple myeloma and 34% with lymphoma. Majority of caregivers were spouses (76%). Inpatients were more likely to be employed and have lymphoma. The overall cohort demonstrated a clinically meaningful decrease (≥4 points) from baseline in mean FACT-F scores (fatigue) at D+7, D+14, and D+28 with slight improvements at D+100 (Table 1). Compared to inpatients, outpatients overall exhibited significantly (p=0.011) greater changes in fatigue from baseline at D+7 and D+14, with comparable change scores at D+28 and D+100 between groups (Figure 1a). Moreover, for all patients, there was a clinically meaningful decrease from baseline in mean QOL scores by FACT-BMT (≥4 points) at D+7 and D+14, and a meaningful improvement at D+100, with no differences between groups (Table 1). On the FACT-BMT subscales, outpatients had overall worsening scores compared to inpatients on the Physical (p=0.029), and Functional Well-Being Subscales (p=0.043) (Figure 1c), while no differences were detected on the Emotional and Social Well-being scales. Health utility scores were also calculated from the EQ-5D-3L, with a significant downward trend in the overall sample at D+7; however, no clinically relevant changes (≥ 0.08) were noted, and results were comparable between groups (Figure 1d). With respect to caregiver QOL, there were no differences in mean change scores between the two groups; however overall, caregivers had a significant improvement at D+100 compared to baseline (p<.05; Figure 1e). Outpatient caregivers experienced higher mean out-of-pocket costs ($1360 vs. $789, p=0.03) with the primary caregiver facing significantly greater total indirect costs ($1960 vs. $1068, p=0.025) (Table 2). For fully employed primary caregivers, the mean lost wages were $1231 for inpatients vs. $2150 for outpatients over the 3 month acute ASCT period. Conclusions There was significant deterioration of various measures of QOL in all patients, irrespective of outpatient or inpatient status. Outpatients, however, reported significantly greater changes in fatigue from baseline at D+7, D+14 and D+28. Caregiver QOL appears comparable between the two modalities. The financial burden on caregivers is high, with significantly higher total indirect costs in outpatient caregivers in the acute post-ASCT period. Figure 1 Figure 1. Disclosures Prica: Kite Gilead: Honoraria; Astra-Zeneca: Honoraria. Chen: Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy. Crump: Novartis: Membership on an entity's Board of Directors or advisory committees; Kyte/Gilead: Membership on an entity's Board of Directors or advisory committees; Epizyme: Research Funding; Roche: Research Funding. Kridel: Gilead Sciences: Research Funding. Kuruvilla: AbbVie: Honoraria; Incyte: Honoraria; Medison Ventures: Honoraria; Merck: Honoraria; Novartis: Honoraria; Gilead: Honoraria; Seattle Genetics: Honoraria; Karyopharm: Honoraria, Other: Data and Safety Monitoring Board; Roche: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; TG Therapeutics: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Antengene: Honoraria. Reece: Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Honoraria; Millennium: Research Funding; Karyopharm: Consultancy, Research Funding; Amgen: Consultancy, Honoraria; GSK: Honoraria.

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HQK-1001 Is Well Tolerated and Augments Hemoglobin F and Hemoglobin Levels In Patients with Beta Thalassemia Intermedia

Blood ◽

10.1182/blood.v116.21.4280.4280 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4280-4280

Author(s):

Suthat Fuchareon ◽

Adlette C. Inati ◽

Noppadol Siritanaratkul ◽

Suzanne Koussa ◽

Ali Taher ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Globin Gene ◽

Beta Thalassemia ◽

Thalassemia Intermedia ◽

Employment Equity ◽

Advisory Committees ◽

Hemoglobin F ◽

Pharmacodynamic Effects ◽

Equity Ownership

Abstract Abstract 4280 Beta thalassemia intermedia syndromes are serious conditions for which there is no satisfactory therapy to correct the underlying globin chain imbalance. Some agents that induce fetal globin gene expression have ameliorated anemia in thalassemia patients by reducing the imbalance in alpha: non-alpha globin synthesis, but none have been broadly accepted or are currently approved by regulatory authorities. HQK-1001 is an oral agent that targets the fetal globin gene promoter, thereby increasing fetal hemoglobin (HbF) expression. It has been well tolerated in single dose and multiple dose escalation clinical studies in healthy volunteers. We now report the results of a randomized, double blind, placebo-controlled, multiple ascending dose Phase I/II trial in 21 adult patients with beta thalassemia intermedia (BTI), including 14 with HbE/ß0 thalassemia and 7 with ß+/ß0 thalassemia (including 12 different beta globin gene mutations). Study medication was taken as a single daily dose for 8 weeks. Four ascending dose levels (10, 20, 30, and 40 mg/kg/day) were sequentially evaluated in 4 dose level cohorts after the preceding dose and schedule were determined safe by an independent and unblinded Safety Monitoring Committee. HQK-1001 was well-tolerated. Adverse events in treated subjects included headache, upper respiratory infection and nausea, but the rates of such events were not markedly different than those observed in the placebo-treated subjects. The 20 mg/kg dose was associated with a 10% mean increase above baseline in HbF, (p< 0.001). Total hemoglobin (Hgb) increased by a mean of 1.1 gram/dL in 3 of 6 treated BTI patients with Mediterranean mutations. F-cells increased over the study period with maximal increases often observed 2 weeks following therapy. Doses higher than 20 mg/kg were not associated with the same magnitude of pharmacodynamic effects. These observations indicate that HQK-1001 is well-tolerated at doses associated with favorable pharmacodynamic effects on Hgb and HbF. These findings with brief treatment provide a rationale for conducting larger and longer studies in BTI patients. Disclosures: Fuchareon: HemaQuest Pharmaceuticals, Inc: Honoraria, Research Funding. Inati:HemaQuest Pharmaceuticals, Inc: Honoraria, Research Funding. Boosalis:HemaQuest Pharmaceuticals, Inc: Equity Ownership, Research Funding. Thein:HemaQuest Pharmaceuticals, Inc: Research Funding. Wallis:HemaQuest Pharmaceuticals: Consultancy, Equity Ownership. Bobbitt:HemaQuest Pharmaceuticals, Inc: Employment, Equity Ownership, Patents & Royalties. Thomson:HemaQuest Pharmaceuticals: Employment, Equity Ownership. Johnson:HemaQuest Pharmaceuticals: Employment, Equity Ownership. Berenson:HemaQuest Pharmaceuticals, Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Perrine:HemaQuest Pharmaceuticals, Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.

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Outcome with Lenalidomide Plus Dexamethasone Followed by Early Autologous Stem Cell Transplantation In the ECOG E4A03 Randomized Clinical Trial

Blood ◽

10.1182/blood.v116.21.38.38 ◽

2010 ◽

Vol 116 (21) ◽

pp. 38-38 ◽

Cited By ~ 11

Author(s):

David Samuel diCapua Siegel ◽

Susanna Jacobus ◽

S. Vincent Rajkumar ◽

Rafat Abonour ◽

Natalie Scott Callander ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Research Funding ◽

Age Groups ◽

Early Mortality ◽

First Year ◽

Age Group ◽

Newly Diagnosed ◽

Advisory Committees

Abstract Abstract 38 INTRODUCTION: Lenalidomide and bortezomib have moved into the management of newly diagnosed multiple myeloma leading to dramatically improved outcomes. As a consequence, the role of upfront autologous peripheral blood stem cell transplant (ASCT) has become more controversial. The ECOG E4A03 clinical trial randomized newly diagnosed MM patients to lenalidomide with high-dose dexamethasone (LD) vs lenalidomide with low-dose dexamethasone (Ld) (Rajkumar et al Lancet Oncol 2010; 11: 29–37). Upon completing four cycles of therapy, pts had the option of ASCT or continuing on the assigned therapy. The purpose of this abstract is to determine the outcome of patients on this trial pursuing early ASCT according to various age-groups. MATERIALS and METHODS: This is a post hoc, retrospective analysis of overall survival within age subgroups stratified by early ASCT status. This is a landmark analysis including only pts surviving the first 4 cycles of therapy. RESULTS: In all three age-groups studied, 1, 2, and 3-year survival probability estimates with ASCT were excellent (Tables 1, 2, and 3). For patients under the age of 65 who survived the first 4 cycles of therapy, overall survival at 3-years was 94% with early ASCT, 78% in pts continuing protocol therapy. Although direct comparison with patients not going to early transplant is not possible because the assignment to early ASCT versus no early ASCT was not randomized, survival with ASCT at 3-years appeared higher. While we attempt to correct for age, the differences may be influenced by other factors such as performance status, comorbidities, response to therapy, etc. The presumption that treatment related mortality (TRM) should be more problematic for older pts undergoing ASCT is addressed by looking at the >65 and >70yo cohorts. In the >65 age group, one-year mortality is similar between the early ASCT population and the no early ASCT population. In the >70 age group, no adverse impact of early ASCT was seen in the first year on overall survival but the sample size is extremely small. In all age groups early ASCT seemed to mitigate some of the survival disadvantage associated with randomization to the LD arm. CONCLUSIONS: This analysis shows that the strategy of lenalidomide plus dexamethasone induction followed by early ASCT has a remarkably good outcome in terms of overall survival in all age groups studied and supports the continued role of early consolidative ASCT in newly diagnosed patients. The risk of early mortality was notably low in the first year in all age groups. The risk of early mortality seems to increase at 2 years for the LD pts not choosing early ASCT and at 3 years for the Ld pts not choosing early ASCT. Selection bias makes it difficult to compare results for pts that chose early ASCT directly to the patients who did not receive early ASCT in this trial. As such, these results emphasize the need for randomized trials investigating the timing of ASCT in myeloma in the era of novel therapy. Disclosures: Siegel: Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Lenalidomide for front line therapy. Abonour:Celgene: Speakers Bureau; Millennium Pharmaceuticals: Speakers Bureau. Callander:Millennium Pharmaceuticals: Research Funding. Fonseca:Amgen: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy, Research Funding; Genzyme: Consultancy; Onyx: Research Funding; Otsuka: Consultancy; Medtronic: Consultancy. Vesole:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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Probing the Origin of Chelatable Iron During Deferiprone and Combination Therapies: Insights From Plasma NTBI and LPI Determinations

Blood ◽

10.1182/blood.v116.21.5158.5158 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5158-5158 ◽

Cited By ~ 1

Author(s):

Yesim Aydinok ◽

Patricia Evans ◽

Chantal Y. Manz ◽

John B. Porter

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Chelation Therapy ◽

Plasma Concentrations ◽

Iron Concentration ◽

Beta Thalassemia ◽

Red Cell ◽

Advisory Committees ◽

Plasma Iron ◽

Iron Excretion

Abstract Abstract 5158 Objectives. Classic clinical and animal studies with deferoxamine (DFO) showed that two major chelatable pools exist in thalassemia major (TM), the first derived from hepatocytes and the second from red cell catabolism. Knowledge about the origin of chelatable iron with deferiprone (DFP) treatment, alone or when combined with DFO, is relatively limited. We hypothesized that changes in plasma iron species during chelation therapy may be proportional to the magnitude of chelatable iron pools. In this study, we have examined the relationship between urinary iron excretion (UIE), transfusional iron loading rates (ILR), liver iron concentration (LIC) and plasma concentrations of non-transferrin bound iron (NTBI) and labile plasma iron (LPI) before and after DFP therapies. Patients and methods. 12 TM patients were randomized to one year of DFP monotherapy (25mg/kg tds) or 9 to DFP at the same dose with the addition of subcutaneous DFO (40-50mg/kg), 2 nights a week (COMB). Plasma samples were taken for NTBI and LPI measurements, at baseline, at 1 week and at 52 weeks. These were obtained at 9am, which was 10hrs following the previous DFP dose, and 24h after the second of two weekly DFO doses for COMB patients. A 24h urine iron was collected at baseline, 1 week and 52 weeks of treatment. The ILR, expressed in mg/kg/day, was calculated from the blood volume transfused during the 1 year study. Results. After 1 week of treatment, there was a significant increase in NTBI from baseline in DFP and in COMB patients. A significant increase in LPI was also seen in DFP patients at this time (p=0.039). In all patients, absolute LPI levels at 1 week correlated with those of NTBI and increments in LPI also correlated with increments in NTBI from baseline to 1 week (r=0.52, p=0.002). Plasma NTBI levels at 1 week were proportional to UIE mg/kg/day)(r=0.51, p= 0.02), to LIC mg/g dry wt (r=0.54, p=0.01) and inversely proportional to the ILR (r=0.74, p=0.0001). By weighting the LIC and ILR pools equally, a combined chelatable pool index was derived: this was significantly proportional to both absolute NTBI at 1 week (r=0.72, p=0.003) and increments in NTBI from baseline. This index was also significantly correlated with UIE (p=0.66, p=0.0017) and with LPI at 1 week. Interpretation and conclusions. Urinary iron excretion with DFP (the predominant route of iron excretion with DFP) and COMB therapy is directly proportional to the LIC, as well as to plasma NTBI and LPI and is inversely proportional to the ILR. This is consistent with the existence of two major chelatable iron pools; the first being liver derived and the second derived from red cell catabolism. This latter pool appears to be larger for those patients who require less blood transfusion and who presumably have greater rates of ineffective eryrthropoiesis. The origin of chelatable iron with this form of COMB therapy, with DFO only two days a week, appears is similar to that of DFP monotherapy. Disclosures: Aydinok: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Off Label Use: Deferiprone and desferrioxamine are indicated and approved for the chelation therapy of iron-overloaded patients with beta thalassemia. The combination of both agents as treatment regimen for patients with beta thalassemia is part of the investigation described in the abstract and is not approved for use. Manz:Lipomed AG: Employment. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Patterns of Care for Patients with Chronic Lymphocytic Leukemia (CLL): The Connect® CLL Disease Registry

Blood ◽

10.1182/blood.v118.21.2864.2864 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2864-2864

Author(s):

Jeff Sharman ◽

Christopher R Flowers ◽

Mark Weiss ◽

David Grinblatt ◽

Charles Farber ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Age Groups ◽

Age Group ◽

First Line ◽

Advisory Committees ◽

First Line Therapy ◽

Line Therapy ◽

Ecog Ps ◽

Group 1

Abstract Abstract 2864 Introduction: Clinical trials have illuminated a number of unique treatment strategies for patients with CLL. The impact of these strategies on routine practice remains unknown as trial participants may not reflect the same population encountered outside of a clinical trial setting. Many questions remain regarding the sequencing of therapies based on age and performance status. By characterizing current patterns of care; patients, treating physicians, and regulatory agencies will be able to understand the current landscape of CLL treatment. The Connect® CLL registry was designed to report the natural history and real world management of patients receiving therapy for CLL. In this first report, we characterize the therapeutic approaches used for the treatment of patients with CLL of different age groups (i.e. < 65 years, 65–75 years, and ≥ 75 years) and with an ECOG PS status score of 0 compared to 1 or greater. Methods: Connect® CLL is a prospective, longitudinal, observational, multi-center registry conducted in community and academic research centers in the United States. At present, 237 sites are actively participating with a projected study enrollment of 1500 patients. Eligible patients are to be enrolled within 2 months of being initiated on any line of therapy; whether initial therapy or salvage therapy. Each patient will be followed for up to 60 months. Clinical data, physician choices, patient-reported health-related quality of life, response and survival are to be collected approximately every 3 months during participation. Results: A total of 607 patients have been enrolled (4% from academic sites) with a median age of 70 years. 198 were < 65 years old (age group 1), 187 were between 65–75 years old (age group 2), and 222 were ≥ 75 years old (age group 3). ECOG status varied across the three age groups, with an ECOG status score of ≥ 1 for 39%, 52%, and 70% of patients respectively. Treatment patterns varied across the age groups and by ECOG status in the 496 patients reporting therapies. The most commonly recorded first-line regimens independent of age included fludarabine (F) cyclophosphamide (C) and rituximab (R) (33%), bendamustine (B) +/− R (19%), F +/− R (15%), or investigational therapy (15%). For second-line regimens and beyond, the most frequently recorded regimen was B +/− R (30%), FCR (23%), other F-based regimens (13%), or investigational therapy (8%). The use of FCR for first-line treatment decreased significantly with increasing age group, (45%, 32%, 20%, for age group 1, 2, 3 respectively, p=0.04, spearman correlation) while use of F +/− R remained level across the age groups (14%, 15%, 15%, respectively). Compared to age group 1, first-line therapy with B +/− R in age groups 2 and 3 (15%, 22%, 21%, respectively) was higher but did not achieve statistical significance. B +/− R represented the most common treatment for all age groups (37%, 26%, 29%, respectively) as second line therapy but did not vary by age (P=0.35). The use of chlorambucil was infrequent in all age groups, but was more common in age group 3 patients compared to the others (P=0.01), in both first-line (2%, 4%, 12%, respectively) and subsequent lines of therapy (0%, 1%, 8%, respectively). Treatment assignments did not vary by ECOG PS score for patients in age group 1. First-line therapy for patients with an ECOG PS score of 0 in age groups 2 and 3 consisted of FCR (32% and 15%, respectively), F +/− R (19% and 15%, respectively), B +/− R (16% and 15%, respectively), and alkylating agents (3% and 23%, respectively). Patients in age groups 2 and 3 with ECOG PS score ≥ 1 received B +/− R regimen (33% and 22%, respectively), FCR (23% and 21%, respectively), F +/− R (14% and 10%, respectively) and alkylating agents (7% and 9%, respectively) as first-line therapy. Further description and clarification on the various treatment regimens based on the three age groups and by ECOG PS score will be presented at the meeting. Conclusion: The Connect® CLL Registry is the largest prospective, multicenter registry in the United States evaluating management for patients with CLL. With the currently available data, we characterize the extent to which age and performance status are associated with treatment selection in both first-line and subsequent lines of therapy in routine practice. As enrollment increases and additional follow-up is completed, the data will provide more extensive and real world overview of the current treatment strategies used in CLL patients. Disclosures: Sharman: Celgene - consulting: Consultancy; Pharmacyclics: Honoraria; Calistoga: Honoraria; Portola pharmaceuticals: Consultancy. Flowers:Consultancy: Celgene, Prescription Solutions, Spectrum (future), Seattle Genetics, Millennium (future), Genentech (unpaid): Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Weiss:Celgene: Consultancy. Grinblatt:Celgene: Honoraria, Speakers Bureau. Kay:Genenetech, Celgene, Hospira,: Research Funding. Kipps:Igenica: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Abbot Industries: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; GSK: Research Funding; Gilead Sciences: Research Funding; Amgen: Research Funding. Lamanna:Celgene Corporation: Advisory board. Pashos:United BioSource Corporation: Research Funding. Flinn:Celgene: Research Funding. Kozloff:Celgene: Consultancy. Lerner:Celgene Connect: Membership on an entity's Board of Directors or advisory committees. Swern:Celgene: Employment. Sullivan:Celgene: Employment. Street:Celgene: Employment. Keating:Celgene Connect: Membership on an entity's Board of Directors or advisory committees.

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Dynamics of Improvement in Health-Related Quality of Life (HRQoL) with Long-Term Eltrombopag Treatment in Adults with Chronic Immune Thrombocytopenia (ITP) in EXTEND.

Blood ◽

10.1182/blood.v120.21.2199.2199 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2199-2199

Author(s):

Kelly M Grotzinger ◽

James B Bussel ◽

Mansoor N Saleh ◽

Christine Bieri ◽

Yuliya Orlova ◽

...

Keyword(s):

Clinical Response ◽

Board Of Directors ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Positive Association ◽

Advisory Committees ◽

Sf 36 ◽

Equity Ownership ◽

Hrqol Assessment

Abstract Abstract 2199 Background: Eltrombopag is an oral thrombopoietin receptor agonist approved for treatment of chronic immune thrombocytopenia (cITP). EXTEND is an ongoing, open-label extension study of long-term cITP treatment with eltrombopag in patients completing a prior eltrombopag study. EXTEND consists of 4 stages (stg): 1, initial treatment with eltrombopag to increase the platelet count (PC) ≥50,000/μL; 2, reduction/elimination of concomitant ITP medication; 3, re-establishing the minimum dose maintaining PC with minimum use of concomitant ITP medication; and 4, long-term treatment. Interim EXTEND data describing efficacy, safety, and HRQoL have been reported (Bussel 2008, 2009, 2012; Grotzinger 2012), but the dynamics of HRQoL effects have not. Previous results reported statistically significant (P<0.05) yet modest clinically meaningful mean improvement from baseline (BL) at every stg of EXTEND for FACIT-Fatigue (FACIT-F) and 6 items from FACT-Thrombocytopenia (FACT-Th6), during Stg 2–4 for the MEI-SF, and Stg 1, 3, and 4 for the physical component summary (PCS) of the SF-36. However, these reports did not address when improvements in fatigue and functioning might occur, nor how HRQoL improvements might be associated with multiple definitions of clinical response. Aim: To assess timing and significance of patients' personal Best Response HRQoL (BRqol) effects of eltrombopag and the association of HRQoL improvements with multiple clinical measures of response for cITP patients in EXTEND. Methods: EXTEND data through Feb 2011 was included; median treatment duration was 2.3 years. Self-reported HRQoL (7-day recall) was obtained at BL and serially afterwards, using the SF-36 mental component summary (MCS) and PCS, FACIT-F, MEI-SF, and FACT-Th6. Proportions of patients reaching BRqol at each stg of EXTEND were assessed for all patients. HRQoL association with clinical response was assessed for all patients with a BL and ≥1 post-BL HRQoL assessment, using 3 definitions of clinical response: • Achieving a doubling of BL PC (Ra) • PC >50,000/μL (Rb) • Achieving guideline-defined (Neunert 2011) responses (Rc), defined as PC ≥100,000/μL (or ≥30,000/μL and >2x BL) on 2 occasions >7 days apart in the absence of bleeding. A similar analysis was completed for a subset of patients with PC <30,000/μL at BL. Results: With minor variation among HRQoL tools, 25–33% of patients reached their BRqol within 90 days and 57–67% within 1 year (Fig 1) of initiating EXTEND. Of those patients who went through each respective stage of EXTEND, 38–43% achieved a BRqol for at least one HRQoL tool during Stg 1 (n=174), 26–35% during Stg 2 (n=54), 33–38% during Stg 3 (n=178), and 44–59% during Stg 4 (n=135). There is little variation in time to BRqol by HRQoL tool among those achieving BRqol in Stg 1, 3, and 4. For the patients who went through Stg 2 and achieved BRqol during Stg 2, median days to BRqol varied by HRQoL tool (eg, 229 for the SF-36 MCS, 84 for the FACT-Th6, and 125 for the SF-36 PCS). All patients completing or continuing in EXTEND reported PC > BL and HRQoL assessment > BL at least once while on therapy. Improvements in MEI-SF, FACIT-F, FACT-Th6, and SF-36 MCS were positively associated (P≤0.05) with each definition of clinical response, except a non-significant association of the MEI-SF with guideline-defined responses (Rc); in addition, there was a positive association (P≤0.05) with SF-36 PCS and PC >50,000/μL (Rb). A similar pattern is evident among the subset of patients with BL PC <30,000/μL. Summary/conclusions: These results suggest BRqol may be achieved by up to 1/3 of patients within 3 months and 2/3 of patients within 12 months of initiating eltrombopag treatment. These data further demonstrate the variability of time to BRqol, and how improvements in HRQoL reflect achievement of multiple clinical goals such as those analyzed in EXTEND. HRQoL improvement may be associated with both simple increases in PC as well as broader definitions of clinical response. Neither guideline-defined responses nor elevating PC to “normal” range are usually the primary goals of treatment of cITP. Critical to note, therefore, is the positive association observed between HRQoL improvements and the straightforward, achievable clinical goals of doubling of PC or achieving PCs >50,000/μL and the time to achieve them. Disclosures: Grotzinger: GlaxoSmithKline: Employment. Bussel:Symphogen: Membership on an entity's Board of Directors or advisory committees; Sysmex: Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; IgG of America: Research Funding; Genzyme: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Portola: Consultancy. Bieri:GlaxoSmithKline: Research Funding. Orlova:GlaxoSmithKline: Research Funding. Brainsky:GlaxoSmithKline: Employment, Equity Ownership, Patents & Royalties.

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