Improvements in Health-Related Quality of Life and Symptoms in Patients with Previously Untreated Chronic Lymphocytic Leukemia: Final Results from the Phase II GIBB Study of the Combination of Obinutuzumab and Bendamustine

Introduction: Longitudinal changes in health-related quality of life (HRQoL) are important in patients with chronic lymphocytic leukemia (CLL). GIBB (NCT02320487) is an open-label, single-arm phase II study of obinutuzumab (GA101; G) in combination with bendamustine (G-Benda) in patients with previously untreated CLL. A previous report from the GIBB study demonstrated an investigator-assessed objective response rate of 89.2%, a complete response rate of 49.0%, and no unexpected safety signals with G-Benda (Sharman et al. J Clin Oncol 2017). Here we report the final HRQoL data over 3 years from the GIBB study. Methods: Enrolled patients received G-Benda by intravenous infusion over six 28-day cycles: G 100mg on Day (D)1, 900mg on D2, and 1000mg on D8 and D15 of Cycle (C)1, then 1000mg on D1 of C2-6; benda 90mg/m2 on D2-3 of C1, and on D1-2 of C2-6. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) includes a global health status measure, 5 functional scales (physical, emotional, cognitive, social, and role functioning), 8 symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, and diarrhea), and an item on financial difficulties (Aaronson et al. J Natl Cancer Inst 1993). The EORTC Quality of Life Questionnaire-Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) is a 16-item module, specific to CLL, containing 4 multi-item scales (fatigue, treatment side effects, disease symptoms, and infection) and 2 single items (social activities and future health worries). Both questionnaires were completed by patients on C1D1 (baseline), C3D1, and C6D1, at the end of induction (EOI) treatment (defined as +28 days from C6D1 or early treatment termination visit), at the response visit (defined as 2-3 months after the EOI treatment for all patients who received study treatment and had not experienced disease progression), and every 3 months thereafter at follow-up visits for up to 2 years. In total, there were 14 timepoints where data were collected. HRQoL scores were linear transformed to a 0-100-point scale. Mean baseline scores and mean score changes from baseline at each visit were evaluated. A threshold of ≥10-point change in score represents a clinically meaningful difference. For symptoms, negative change scores from baseline reflect an improvement in symptom burden. For global health status and functioning, positive change scores from baseline reflect improvements. Results: The trial enrolled 102 patients. Median age was 61 years and 68.4% of patients were male. Ninety-eight patients (96%) completed a questionnaire at baseline and at least 1 other questionnaire during a follow-up visit. Questionnaire completion rates at 14 time points ranged from 96% at baseline to 66% at 27 months follow-up (Table 1). According to the EORTC QLQ-C30 (Figure 1), improvements were observed for global health status at all follow-up visits, and clinically meaningful improvements were observed at the response visit, 3 months follow-up, and 27 months follow-up. Clinically meaningful improvements in role functioning were observed at EOI and persisted throughout the 27-month follow-up. For fatigue, clinically meaningful improvements were observed at every visit starting from the end of treatment (EOT) visit. Improvements were also observed for insomnia with mean reductions from baseline ≥10 points at various time points during follow-up. There was no worsening in other patient-reported symptoms or functional status over time. Similarly, with the EORTC QLQ-CLL16 (Figure 2), clinically meaningful improvements in symptoms were observed for fatigue, disease symptoms, and future health worries during treatment, at the EOT and/or throughout the follow-up. The largest improvement was observed for fatigue (-24.7) at the 24-month follow-up and future health worries (-25.4) at the 27-month follow-up. Conclusions: We previously reported that G-Benda is an effective regimen for first-line treatment of CLL with no unexpected safety signals. The HRQoL data from the GIBB trial suggest that G-Benda treatment consistently improved patient HRQoL over time. Several clinically meaningful improvements were observed in HRQoL, including global health status, functioning, symptoms, and future health worries. Disclosures Danilov: AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; MEI: Research Funding; Bristol-Meyers Squibb: Research Funding; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Takeda Oncology: Research Funding; Genentech: Consultancy, Research Funding; Bristol-Meyers Squibb: Research Funding; Takeda Oncology: Research Funding; Aptose Biosciences: Research Funding; Aptose Biosciences: Research Funding; Janssen: Consultancy; Pharmacyclics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Celgene: Consultancy; Pharmacyclics: Consultancy; Janssen: Consultancy; Curis: Consultancy; Seattle Genetics: Consultancy; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Gilead Sciences: Consultancy, Research Funding; Bayer Oncology: Consultancy, Research Funding; Curis: Consultancy; Seattle Genetics: Consultancy; MEI: Research Funding; TG Therapeutics: Consultancy; Celgene: Consultancy; Gilead Sciences: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Abbvie: Consultancy; Abbvie: Consultancy. Yimer:AstraZeneca: Speakers Bureau; Janssen: Speakers Bureau; Seattle Genetics: Honoraria; Celgene: Honoraria; Clovis Oncology: Equity Ownership; Puma Biotechnology: Equity Ownership; Amgen: Consultancy. Boxer:Gerson Lerman: Consultancy; Best Doctors: Consultancy; Takeda: Honoraria, Speakers Bureau; AbbVie: Honoraria, Speakers Bureau. Burke:Celgene: Consultancy; Gilead: Consultancy; Roche/Genentech: Consultancy. Babu:Genentech: Research Funding. Li:Genentech: Employment; Roche: Equity Ownership. Mun:Genentech: Employment, Equity Ownership. Trask:Genentech: Employment, Equity Ownership. Masaquel:Roche: Equity Ownership; Genentech: Employment. Sharman:Acerta: Consultancy, Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding. OffLabel Disclosure: GAZYVA (obinutuzumab) is a CD20-directed cytolytic antibody and is indicated: in combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia; in combination with bendamustine followed by GAZYVA monotherapy, for the treatment of patients with follicular lymphoma (FL) who relapsed after, or are refractory to, a rituximab-containing regimen

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Improvements in Health-Related Quality of Life and Symptoms in Patients with Previously Untreated Chronic Lymphocytic Leukemia: Results from the Phase II GIBB Study of the Combination of Obinutuzumab and Bendamustine

Blood ◽

10.1182/blood.v130.suppl_1.683.683 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 683-683

Author(s):

Jeffrey P. Sharman ◽

Habte Yimer ◽

Michael Boxer ◽

Nicholas Di Bella ◽

Sunil Babu ◽

...

Keyword(s):

Quality Of Life ◽

Chronic Lymphocytic Leukemia ◽

Research Funding ◽

Lymphocytic Leukemia ◽

Induction Treatment ◽

Future Health ◽

Employment Equity ◽

Equity Ownership ◽

Eortc Qlq

Abstract Introduction: Maintenance and/or improvements in health-related quality of life (HRQoL) are important in patients with chronic lymphocytic leukemia (CLL). GIBB (NCT02320487) is an ongoing, open-label, single-arm Phase II study of the combination of obinutuzumab (GA101; G) and bendamustine (B) (BG) in patients with previously untreated CLL. A previous report from the GIBB study demonstrated an investigator-assessed objective response rate of 89.2%, a complete response rate of 49.0%, and no unexpected safety signals with BG (Sharman et al. ASCO 2017). Here, we present the HRQoL data from GIBB. Methods: In the GIBB trial, patients received BG by intravenous infusion over six 28-day cycles: obinutuzumab 100mg on Day (D)1, 900mg on D2, and 1000mg on D8 and D15 of Cycle 1, then 1000mg on D1 of Cycles 2-6; B 90mg/m2 on D2-3 of Cycle 1, and on D1-2 of Cycles 2-6. The European Organisation for Research and Treatment of Cancer Quality of Life - Core (EORTC QLQ-C30) questionnaire includes a global health status measure, 5 functional scales (physical, emotional, cognitive, social, and role functioning), 8 symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, and diarrhea), and an item on financial difficulties (Aaronson et al. J Natl Cancer Inst 1993). The EORTC Quality of Life Questionnaire-Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) is a 16-item module, specific to CLL, containing 4 multi-item scales (fatigue, treatment side effects, disease symptoms, and infection) and 2 single items (social activities and future health worries; EORTC website, accessed July 25, 2017). Both questionnaires were completed by patients on D1 of Cycles 1 (baseline), 3, and 6, at the end of induction treatment (defined as +28 days from D1 of Cycle 6 or early treatment termination visit), at the response visit (defined as 2-3 months after the end of induction treatment, for all patients who received study treatment and had not experienced disease progression), and every 3 months thereafter at follow-up visits. HRQoL scores were linear transformed to a 0-100 point scale. Mean baseline scores and mean score changes at each visit were evaluated. A threshold of ≥10-point change in score represents a clinically meaningful difference. Results: Of 102 patients enrolled in the trial, 98 completed a questionnaire at baseline and at least one other questionnaire during a follow-up visit. Questionnaire completion rates were 86.7%, 77.6%, 80.6%, and 86.7% at Cycles 3, 6, at the end of induction treatment, and at the response visit, respectively. Median age was 61 years and 68.4% of patients were male. According to the EORTC QLQ-C30 (Figure 1), clinically meaningful improvements were observed for global health status at the response visit, and for role functioning at the end of induction treatment and at the response visit. A trend was observed for improvement in emotional functioning. The greatest improvement in HRQoL score was observed for fatigue (mean baseline score: 37.64), with mean changes from baseline of −4.01, −5.48, −11.67, and −16.34 at Cycles 3, 6, at the end of induction treatment, and at the response visit, respectively. Improvements were also observed for insomnia (mean baseline score: 33.33), with mean changes from baseline of −6.59, −9.09, −9.7, and −10.98, respectively. There was no worsening in other patient-reported symptoms or functional status over time. Similarly, with the EORTC QLQ-CLL16 (Figure 2), clinically meaningful improvements in symptoms were observed for fatigue, disease symptoms, and future health worries during treatment, at the end of induction treatment and/or at the response visit. The greatest change at the response visit was observed for fatigue (−21.23) and future health worries (−20.24). A positive trend was also observed for improvements in the social activities scale. Conclusions: We previously reported that BG is an effective regimen for first-line treatment of CLL with no unexpected safety signals. In addition, the HRQoL data from the GIBB trial suggest that BG treatment improves patient HRQoL. Several clinically meaningful improvements were observed in HRQoL, including global health status, functioning, symptoms, and future health worries at the time of the response visit. Disclosures Sharman: Acerta: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Genentech: Consultancy, Honoraria, Other: GIBB is sponsored by Genentech Inc. Third-party editorial support, under the direction of Anthony Masaquel, was provided by Lynda McEvoy of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Yimer: Juno pharma: Equity Ownership; Bellucum Pharma: Equity Ownership. Babu: Alexion: Speakers Bureau; Abbvie: Consultancy. Li: Genentech: Employment, Equity Ownership. Mun: Genentech: Employment, Equity Ownership. Trask: Genentech: Employment, Other: stock. Masaquel: Genentech Inc.: Employment, Other: I Receive Roche stock options. Reyes: Genentech Inc.: Employment, Equity Ownership.

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Five-Year Experience with Single-Agent Ibrutinib in Patients with Previously Untreated and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia

Blood ◽

10.1182/blood.v128.22.233.233 ◽

2016 ◽

Vol 128 (22) ◽

pp. 233-233 ◽

Cited By ~ 53

Author(s):

Susan M. O'Brien ◽

Richard R. Furman ◽

Steven E. Coutre ◽

Ian W. Flinn ◽

Jan Burger ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Board Of Directors ◽

Research Funding ◽

Single Agent ◽

Lymphocytic Leukemia ◽

Advisory Committees ◽

Equity Ownership ◽

Grade 3 ◽

Over Time

Abstract Background: Ibrutinib (ibr), a first-in-class, once-daily Bruton's tyrosine kinase inhibitor, is approved by the US FDA for treatment of patients (pts) with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) including pts with del17p. The phase 1b/2 PCYC-1102 trial showed single-agent efficacy and tolerability in treatment-naïve (TN; O'Brien, Lancet Oncol 2014) and relapsed/refractory (R/R) CLL/SLL (Byrd, N Engl J Med 2013). We report efficacy and safety results of the longest follow-up to date for ibr-treated pts. Methods: Pts received 420 or 840 mg ibr QD until disease progression (PD) or unacceptable toxicity. Overall response rate (ORR) including partial response (PR) with lymphocytosis (PR-L) was assessed using updated iwCLL criteria. Responses were assessed by risk groups: unmutated IGVH, complex karyotype (CK; ≥3 unrelated chromosomal abnormalities by stimulated cytogenetics assessed by a reference lab), and in hierarchical order for del17p, then del11q. In the long-term extension study PCYC-1103, grade ≥3 adverse events (AEs), serious AEs, and AEs requiring dose reduction or discontinuation were collected. Results: Median age of the 132 pts with CLL/SLL (31 TN, 101 R/R) was 68 y (range, 37-84) with 43% ≥70 y. Baseline CK was observed in 41/112 (37%) of pts. Among R/R pts, 34 (34%) had del17p, 35 (35%) del11q, and 79 (78%) unmutated IGVH. R/R pts had a median of 4 prior therapies (range, 1-12). Median time on study was 46 m (range, 0-67) for all-treated pts, 60 m (range, 0-67.4) for TN pts, and 39 m (range, 0-67) for R/R pts. The ORR (per investigator) was 86% (complete response [CR], 14%) for all-treated pts (TN: 84% [CR, 29%], R/R: 86% [CR, 10%]). Median progression-free survival (PFS) was not reached (NR) for TN and 52 m for R/R pts with 60 m estimated PFS rates of 92% and 43%, respectively (Figure 1). In R/R pts, median PFS was 55 m (95% confidence intervals [CI], 31-not estimable [NE]) for pts with del11q, 26 m (95% CI,18-37) for pts with del17p, and NR (95% CI, 40-NE) for pts without del17p, del11q, trisomy 12, or del13q. Median PFS was 33 m (95% CI, 22-NE) and NR for pts with and without CK, and 43 m (95% CI, 32-NE) and 63 m (95% CI, 7-NE) for pts with unmutated and mutated IGVH, respectively(Figure 2). Among R/R pts, median PFS was 63 m (95% CI, 37-NE) for pts with 1-2 prior regimens (n=27, 3 pts with 1 prior therapy) and 59 m (95% CI, 22-NE) and 39 m (95% CI, 26-NE) for pts with 3 and ≥4 prior regimens, respectively. Median duration of response was NR for TN pts and 45 m for R/R pts. Pts estimated to be alive at 60 m were: TN, 92%; all R/R, 57%; R/R del17p, 32%; R/R del 11q, 61%; R/R unmutated IGVH, 55%. Among all treated pts, onset of grade ≥3 treatment-emergent AEs was highest in the first year and decreased during subsequent years. With about 5 years of follow-up, the most frequent grade ≥3 AEs were hypertension (26%), pneumonia (22%), neutropenia (17%), and atrial fibrillation (9%). Study treatment was discontinued due to AEs in 27 pts (20%) and disease progression in 34 pts (26%). Of all treated pts, 38% remain on ibr treatment on study including 65% of TN pts and 30% of R/R pts. Conclusions: Single-agent ibrutinib continues to show durable responses in pts with TN or R/R CLL/SLL including those with del17p, del11q, or unmutated IGVH. With extended treatment, CRs were observed in 29% of TN and 10% of R/R pts, having evolved over time. Ibrutinib provided better PFS outcomes if administered earlier in therapy than in the third-line or beyond. Those without CK experienced more favorable PFS and OS than those with CK. Ibrutinib was well tolerated with the onset of AEs decreasing over time, allowing for extended dosing for 65% of TN and 30% of R/R pts who continue treatment. Disclosures O'Brien: Janssen: Consultancy, Honoraria; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding. Furman:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Speakers Bureau. Coutre:Janssen: Consultancy, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Research Funding. Flinn:Janssen: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Gilead Sciences: Research Funding; ARIAD: Research Funding; RainTree Oncology Services: Equity Ownership. Burger:Pharmacyclics, LLC, an AbbVie Company: Research Funding; Gilead: Research Funding; Portola: Consultancy; Janssen: Consultancy, Other: Travel, Accommodations, Expenses; Roche: Other: Travel, Accommodations, Expenses. Sharman:Gilead: Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding. Wierda:Abbvie: Research Funding; Genentech: Research Funding; Novartis: Research Funding; Acerta: Research Funding; Gilead: Research Funding. Jones:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding. Luan:AbbVie: Equity Ownership; Pharmacyclics, LLC, an AbbVie Company: Employment, Other: Travel, Accommodations, Expenses. James:AbbVie: Equity Ownership; Pharmacyclics, LLC, an AbbVie Company: Employment. Chu:Pharmacyclics, LLC, an AbbVie Company: Employment; AbbVie: Equity Ownership.

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Patient-Reported Outcomes (PRO) Data from Patients (Pts) with Essential Thrombocythemia (ET) Enrolled in the MOST Study

Blood ◽

10.1182/blood-2019-124527 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1665-1665

Author(s):

Ellen K. Ritchie ◽

Anas Al-Janadi ◽

Philomena Colucci ◽

Patricia Kalafut ◽

Dilan Paranagama ◽

...

Keyword(s):

Quality Of Life ◽

Global Health ◽

Research Funding ◽

Symptom Burden ◽

Advisory Board ◽

Employment Equity ◽

Scale Scores ◽

Equity Ownership ◽

Eortc Qlq

Introduction: ET is a chronic myeloproliferative neoplasm (MPN) characterized by thrombocytosis and an increased risk for thrombotic and hemorrhagic events. ET can be associated with substantial symptom burden, impaired quality of life (QoL), and reduced survival. PRO data pertaining to the impact of ET on QoL and symptom burden in these pts are limited. The ongoing Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) was designed to collect data about the demographics, disease burden, PROs, and management of pts with ET or myelofibrosis (MF) in clinical practices throughout the United States. This analysis describes PROs from pts with ET enrolled in MOST. Methods: MOST is a longitudinal, multicenter, noninterventional, prospective, observational study (NCT02953704). Eligible adults with ET were ≥60 years of age, had a history of thrombotic events, or were receiving ET-directed therapy. PROs were collected in conjunction with usual-care visits approximately every 6 months over a planned observation period of 36 months. Patient-reported symptom burden was assessed with the disease-specific MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), composed of 10 items (fatigue, early satiety, abdominal discomfort, inactivity, concentration problems, night sweats, itching, bone pain, fever [>100oF], weight loss). The MPN-SAF numbness/tingling item was also included in the questionnaire but was not included in the TSS calculation. Symptom severity was graded from 0 (absent) to 10 (worst imaginable), with a possible TSS ranging from 0 to 100. Health-related QoL was evaluated with the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30 v3.0), composed of 5 functional scales, 3 symptom scales, 6 additional single-symptom items, and a global health/QoL scale. For functional and global health/QoL scales, higher scores indicate higher functioning and better global health/QoL, respectively. For symptom scales/items, higher scores indicate greater symptom burden. High-risk pts and low-risk pts receiving ET-directed therapy (excluding aspirin only) with baseline PRO data were included in this analysis. Data were summarized with descriptive statistics. Results: The MOST study enrolled 1234 pts with ET between Nov 29, 2016 and March 29, 2019 at 124 sites. Of these pts, 794 qualified for this analysis (data cut-off date, June 17, 2019); median age was 70 (range, 19-93) years, 80% were ≥60 years of age, 68% were women, 90% were white, 42% were working full or part-time, and 4% had a documented family history of MF, ET, or polycythemia vera. The majority of pts (87%) had high-risk ET. At enrollment, 768 pts completed the MPN-SAF. Mean (SD) TSS was 17.1 (15.6); 33% of pts had TSS ≥20. Women had higher mean (SD) TSS than men (18.5 [15.8] vs 14.2 [14.9]) and had higher mean individual symptom scores, except for weight loss and fever. The highest mean (SD) individual symptom scores were fatigue (3.4 [2.7]), numbness/tingling (2.3 [3.0]), inactivity (2.3 [2.8]), and early satiety (2.3 [2.7]) (Fig A). The most frequently reported severe symptoms (ie, score ≥7) were fatigue (17% [127/746]), numbness/tingling (14% [107/767]), and inactivity (11% [86/762]). At enrollment, 794 pts completed the EORTC QLQ-C30. The highest mean (SD) symptom scale scores (score ≥15) were fatigue (29.6 [25.8]), insomnia (28.6 [30.6]), pain (22.1 [27.9]), dyspnea (17.2 [25.5]), and constipation (15.7 [25.2]) (Fig B). The mean (SD) global health status/QoL score was 72.7 (21.9); functional scores ranged from 79.9 (21.9) for emotional functioning to 85.2 (24.1) for social functioning (Fig C). The average functional scale scores and symptom scale scores indicate higher functioning and less symptom burden, respectively, in men vs women. Conclusion: Pts with ET experienced a high symptom burden; fatigue was the most common and highest in severity. Symptom burden and quality of life scores in the current study were similar to prior reports (Emanuel J Clin Oncol 2012; Scherber Blood 2011). Women reported higher symptom burden than men in both the MPN-SAF and EORTC QLQ-30. Of note, numbness/tingling, which is not included in the MPN-SAF TSS calculation, was one of the most frequently reported severe symptoms for pts with ET in MOST. Future analyses from this trial will continue to increase understanding of the symptom burden and its impact on QoL in pts with ET. Disclosures Ritchie: Celgene, Incyte, Novartis, Pfizer: Consultancy; Genentech: Other: Advisory board; Tolero: Other: Advisory board; Pfizer: Other: Advisory board, travel support; agios: Other: Advisory board; Celgene: Other: Advisory board; Jazz Pharmaceuticals: Research Funding; Celgene, Novartis: Other: travel support; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Ariad, Celgene, Incyte, Novartis: Speakers Bureau. Al-Janadi:Incyte: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Celgene: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Genentech/Abbvie: Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Genentech/Roche: Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Sandoz-Novartis: Consultancy, Honoraria; Alexion Pharmaceuticals: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; MEI Pharma: Research Funding; Seattle Genetics: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses. Colucci:Incyte: Employment, Equity Ownership. Kalafut:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Mesa:Genotech: Research Funding; Promedior: Research Funding; Sierra Onc: Consultancy; Celgene: Research Funding; AbbVie: Research Funding; Novartis: Consultancy; La Jolla Pharma: Consultancy; CTI Biopharma: Research Funding; Samus: Research Funding; Incyte: Research Funding.

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Quality-of-Life Outcomes in Patients with Relapsed or Refractory Multiple Myeloma Treated with Elotuzumab Plus Lenalidomide/Dexamethasone or Lenalidomide/Dexamethasone: Final Analysis of the Phase 3 ELOQUENT-2 Study

Blood ◽

10.1182/blood-2019-122668 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2190-2190 ◽

Cited By ~ 1

Author(s):

David Cella ◽

Jan McKendrick ◽

Harrison Davis ◽

Ravi Vij ◽

Clara Chen

Keyword(s):

Quality Of Life ◽

Global Health ◽

Research Funding ◽

Final Analysis ◽

Pain Severity ◽

Global Health Status ◽

Treatment Groups ◽

Eortc Qlq

Introduction: The development of numerous novel therapies for the treatment of relapsed or refractory multiple myeloma (MM) has resulted in improved response rates and durable responses that prolong survival. Assessment of health-related quality of life (HRQoL) has therefore become increasingly important as HRQoL decreases with increasing lines of therapy (LoTs) (Despiégel et al. Clin Lymphoma Myeloma Leuk 2019). In the phase 3 ELOQUENT-2 study (NCT01239797), elotuzumab (E) plus lenalidomide/dexamethasone (Ld) showed a 30% reduction in the risk of progression/death versus Ld in patients with relapsed or refractory MM and 1-3 prior LoTs (median follow-up: 24.5 months; Lonial et al. N Engl J Med 2015). The initial analysis of patient-reported outcomes (PROs) from ELOQUENT-2 at a 3-year extended follow-up showed that the improvement in efficacy observed with ELd was achieved without a detriment to HRQoL (Cella et al. Ann Hematol 2018). Here we present the final analysis of PRO data from ELOQUENT-2. Methods: In ELOQUENT-2, patients with relapsed or refractory MM and 1-3 prior LoTs were randomized 1:1 to receive ELd or Ld in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The Brief Pain Inventory-Short Form (BPI-SF; pain severity, pain interference, and worst pain), the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 questionnaire (QLQ-C30; prespecified key domains were physical function, fatigue, global health status/QoL, and pain), and the myeloma-specific module (QLQ-MY20; includes assessment of symptoms and treatment side effects) were administered at baseline (BL), on Day 1 of each treatment cycle, and at the end of treatment/study withdrawal. All randomized patients with ≥1 post-BL assessment were included in each PRO analysis. Overall mean change from BL was compared between treatment groups based on a mixed-effect model for repeated measures; statistical tests for the overall population only included treatment cycles with >30 patients in each treatment group. A paired t-test was used to compare scores at each cycle with BL; an unpaired t-test compared mean values between treatment groups. BPI-SF scores range from 0-10 with lower scores representing better pain outcomes. EORTC QLQ-C30 scores range from 0-100 with higher scores representing better physical functioning and global health status/QoL, and worse fatigue and pain; EORTC QLQ-MY20 scores range from 0-100 with higher scores representing worse symptoms and problems. Results: In total, 646 patients were treated with ELd (n=321) or Ld (n=325); 319 and 311 patients had ≥1 post-BL assessment and were included in the PRO analysis, respectively (minimum follow-up: 70.6 months). BL BPI-SF mean scores for ELd versus Ld were low across all domains: pain severity (2.6 vs 2.9), pain interference (2.5 vs 2.8), and worst pain (3.6 vs 3.8). Scores for all BPI-SF domains remained stable over the course of the study (eg, pain severity: Figure A). ELd-treated patients with BL moderate/severe pain severity (score of ≥5) had significantly lower mean pain severity scores versus Ld-treated patients in Cycles 1-5. A higher proportion of clinical responders (complete or partial response per European Group for Blood and Marrow Transplantation criteria) versus non-responders had a sustained reduction in pain score across all BPI-SF domains: pain severity (18% vs 6%), pain interference (15% vs 6%), and worst pain (30% vs 13%); the difference in time to sustained improvement was not statistically significant between the clinical responders and non-responders for any pain endpoint. For both treatment groups, there was no clinically meaningful change (≥10 points) from BL scores at any cycle (>30 patients) across all key domains for EORTC QLQ-C30 (eg, global health status/QoL: Figure B) and QLQ-MY20. Conclusions: This final analysis of PROs in ELOQUENT-2 confirms that the efficacy benefits observed with addition of elotuzumab to Ld in patients with relapsed or refractory MM treated with 1-3 prior LoTs were achieved without negatively affecting HRQoL compared with Ld. Study support: BMS. Medical writing: Kenny Tran, Caudex, funded by BMS. Disclosures Cella: FACIT.org: Equity Ownership. McKendrick:PRMA Consulting Ltd.: Employment, Other: I am employed by PRMA Consulting Ltd who provide consulting services to a number of pharmaceutical companies. Davis:PRMA Consulting Ltd.: Employment, Other: I am employed by PRMA Consulting Ltd who provide consulting services to a number of pharmaceutical companies.. Vij:Sanofi: Honoraria; Karyopharm: Honoraria; Janssen: Honoraria; Genentech: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Takeda: Honoraria, Research Funding. Chen:Bristol-Myers Squibb: Employment.

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Allogeneic Transplantation from an HLA-Matched Family Donor in First Complete Remission of Acute Myeloid Leukemia Had an Adverse Impact on Quality of Life in Patients Followed for at Least Five Years after Treatment: A Survey of the German AML Intergroup on 525 Patients.

Blood ◽

10.1182/blood.v106.11.747.747 ◽

2005 ◽

Vol 106 (11) ◽

pp. 747-747

Author(s):

Dorle Messerer ◽

Jutta Engel ◽

Jörg Hasford ◽

Markus Schaich ◽

Silke Soucek ◽

...

Keyword(s):

Quality Of Life ◽

Health Status ◽

Global Health ◽

Odds Ratio ◽

Cardiac Insufficiency ◽

Global Health Status ◽

Concomitant Disease ◽

The Impact

Abstract The impact of allogeneic blood stem cell transplantation (Allo-SCT) in comparison to conventional chemotherapy (CCT) in AML on quality of life remains unclear mainly due to a lack of studies with long term follow-up. Therefore the German AML-Intergroup initiated a survey on quality of life for patients treated within 1 of 8 German prospective multicenter treatment trials. All patients completed a self-report questionnaire either when they returned for follow-up outpatient visits or by mail. Patients completed the EORTC Quality of Life-Core Questionnaire (QLQ-C30) supplemented by self-assessed concomitant diseases, late treatment effects and demographic details including percentage of disability. 525 patients (median age: 46 years at diagnosis; median follow up period: 9 years) returned their questionnaires, 244 after SCT in 1. CR (189 allo; 55 auto) and 281 after CCT. Recovery-rate of the questionnaires was 55% ranging from 40% to 79% in the different trial cohorts. Due to low numbers after auto-SCT these patients were excluded from further analysis. The ECOG activity index revealed normal activity in 40% and 58% and disabled person card in 63% and 37% of the patients in the allo-SCT and CCT groups, respectively. Impaired vision, cataract surgery, chronic skin disorders and treatment of hormonal disorders were reported significantly more often in allo-SCT-patients, whereas osteoarthritis, cardiac insufficiency and unspecific back pain were slightly more frequent in CCT patients, mainly due to a higher median age in the CCT-group. All QLQC-30 functions except physical functioning and pain were in favor of CCT (p<0.001 in each variable). Problems in leisure-time activity, evenness and social life (friends and family) as well as financial management were significantly more frequent in patients after Allo-SCT than in patients after CCT, whereas the general assessment of positive attitude in life showed no difference between the two groups (62% CCT and 64% Allo-SCT). Multivariate logistic regression models on global health status and fatigue were performed. Actually concomitant disease (odds ratio 6.68 95%-CI 3.83–11.66), age > 45 years (odds-ratio 2.57 95%-CI 1.47–4.50) and Allo-SCT (odds ratio 2.10 95%-CI 1.20 – 3.69) showed significant adverse effect on global health status. Similarly unfavorable effects were evaluated for actually concomitant disease and Allo-SCT on fatigue. These results indicate that Allo-SCT compared to intensive chemotherapy had a significant negative impact on quality of life and this needs to be considered when reviewing treatment options.

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Venetoclax Improves Quality of Life for Patients with Elapsed/Refractory Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood-2018-99-117127 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4858-4858 ◽

Cited By ~ 1

Author(s):

Tara Cochrane ◽

Tatiana Chagorova ◽

Tadeusz Robak ◽

Su-Peng Yeh ◽

Evgeny Nikitin ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

Lymphocytic Leukemia ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership ◽

Eortc Qlq ◽

The Impact

Abstract INTRODUCTION: Patients with chronic lymphocytic leukemia (CLL) have significantly decreased health related quality of life (HRQoL), particularly related to severe and progressive fatigue. Side effects of chemotherapies and the emotional burden of living with an often poor prognosis disease also negatively impact patient HRQoL. Venetoclax, an oral agent that targets the anti-apoptotic protein BCL2, has demonstrated high rates of deep and durable response in patients with relapsed/refractory (R/R) CLL, including those with 17p deletions, and has been shown to facilitate clinically relevant improvement in several key aspects of functioning and HRQoL. We evaluated the impact of venetoclax monotherapy on the quality of life of patients with R/R CLL. METHODS: VENICE II is an ongoing open-label, phase 3b, multicenter study (NCT02980731) that assessed patient-reported HRQoL in patients who were ≥18 years old with R/R CLL, including those with 17p deletion, TP53 mutations, and/or prior experience with B-cell receptor pathway inhibitor-containing (BCRi) therapy, treated with venetoclax monotherapy (5-week dose-titration, starting at 20mg once daily, then increased weekly to 50 mg, 100 mg, 200 mg, and 400 mg, followed by 400mg once daily). The primary endpoint was the mean change from baseline to Week 48 in the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) subscale. HRQoL subscales analyzed included: Global Health Status, Role Functioning, Emotional Functioning, Cognitive Functioning, Social Functioning, and Fatigue. The impact on QoL was also assessed on the CLL Module (EORTC QLQ-CLL16). Relevance of mean changes in HRQoL measures from baseline were analyzed based on minimum important difference (MID); a 5-10 point change was defined as MID, and >10 points was considered clinically meaningful.(Osoba, D., et al. J Clin Oncol. 1998;16:139-44. Osoba, D., et al. Qual Life Res. 1994;3:353-64.) Safety and adverse events (AEs) were also monitored. RESULTS: As of the data cutoff, April 30, 2018, the median time on study was 28 weeks (range: 1 - 73) and the median time on therapy was 23 weeks (range: 0.1 - 69) in this ongoing study. Of the 169 treated patients, 70% were male; the median age was 65 years (range: 24 - 86). Among those with available data, 17p deletions and TP53 mutations were confirmed in 34% (41/122) and 38% (19/50) of patients, respectively. Overall, 38%, 20%, and 42% of patients had one, two, and three (or more) prior lines of therapy respectively; 21% of patients had prior BCRi therapy. Clinically meaningful improvements from baseline were observed by week 12 and were sustained through week 48 in the EORTC-QLQ-C30 global health status and the role function, social function, and fatigue subscales (Table and Figure 1A) and EORTC-QLQ-CLL16 future health and disease effect subscales (Table and Figure 1B). Eighty-two percent of patients had at least 1 AE; most commonly observed AEs (≥10% of patients) were neutropenia (35%), diarrhea (17%), thrombocytopenia (15%), anemia (12%), nausea (12%), and upper respiratory infection (11%). Twenty-eight percent of patients had a serious AE, of which the most common were pneumonia (5%), febrile neutropenia (4%) and pyrexia (3%). Five percent of patients discontinued the study due to an AE. CONCLUSIONS: Preliminary data from this ongoing study suggest that patients with R/R CLL experienced improvement in several key aspects of functioning and quality of life with venetoclax monotherapy within the first 12 weeks which is sustained over time. Venetoclax monotherapy was well tolerated in R/R CLL patients. These findings are consistent with previous studies of R/R CLL patients who received venetoclax monotherapy. Disclosures Cochrane: Janssen: Membership on an entity's Board of Directors or advisory committees; Cilag: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Calgene: Honoraria; Amgen: Honoraria; Novartis: Honoraria; MSD: Honoraria. Robak:AbbVie, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy. Yeh:GNT Biotech & Medicals Crop.: Research Funding. Nikitin:AbbVie, Inc: Speakers Bureau. Breuleux:Roche: Employment, Equity Ownership; Gilead: Equity Ownership; Basilea: Patents & Royalties; Novartis: Patents & Royalties. Masud:AbbVie, Inc: Employment, Equity Ownership. Sail:AbbVie, Inc: Employment, Equity Ownership. Komlosi:AbbVie, Inc: Employment, Equity Ownership. Anderson:Walter and Eliza Hall: Employment, Patents & Royalties; AbbVie, Inc: Research Funding; Genentech: Research Funding.

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Clinically Important Difference for the FACIT-Fatigue Scale in Paroxysmal Nocturnal Hemoglobinuria: A Derivation from International PNH Registry Patient Data

Blood ◽

10.1182/blood-2021-153127 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1952-1952

Author(s):

David Cella ◽

Peter Johansson ◽

Yasutaka Ueda ◽

Ioannis Tomazos ◽

Philippe Gustovic ◽

...

Keyword(s):

Quality Of Life ◽

Health Status ◽

Rare Disease ◽

Research Funding ◽

Paroxysmal Nocturnal Hemoglobinuria ◽

Subscale Score ◽

Fatigue Score ◽

Clinically Important Difference

Abstract Background: Fatigue is a common symptom associated with paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab, a C5 inhibitor approved for treatment of PNH, has been shown to significantly alleviate fatigue, as indicated by reduced scores on the Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-Fatigue). FACIT-Fatigue scores range from 0-52 (higher scores indicate less fatigue); this assessment is validated for use in patients with PNH and has been used extensively both in clinical trials and in the International PNH Registry. In patients with cancer, the FACIT-Fatigue clinically important difference (CID) is estimated to be improvement of 3-5 points. This CID is commonly applied in PNH studies; however, no disease-specific CID for FACIT-Fatigue has been estimated in patients with PNH. A PNH-specific CID would be informative in evaluating changes in fatigue impact and could serve as a more robust criterion for evaluating treatment efficacy. The objective of this analysis was to determine the FACIT-Fatigue CID for patients with PNH using distribution- and anchor-based approaches and real-world data from the International PNH Registry. Methods: Adults with PNH who initiated eculizumab within 28 days of enrollment in the PNH Registry as of January 2021 with non-missing baseline FACIT-Fatigue scores were included in the analysis. FACIT-Fatigue scores were assessed at baseline and 6, 12, 24, and 36 months. Two distribution-based CID estimates were calculated using: 1) 0.5 × SD and 2) standard error of measurement (SEM). The SEM was calculated as SD−sqrt(1-α), where α represents the internal consistency measurement Cronbach's alpha. Cronbach's alpha was calculated from the 13 FACIT-Fatigue subscales. Anchor-based estimates considered 2 continuous patient-reported outcome variables: 1) European Organization for Research and Treatment of Cancer (EORTC) Global Health Status Quality of Life (QoL) summary score (quartiles; higher scores indicate better quality of life), and 2) EORTC Global Health Status Fatigue Subscale score (quartiles; lower scores indicate less fatigue). The baseline FACIT-Fatigue score was calculated for each predefined categorization of the anchors; the mean of differences in FACIT-Fatigue between adjacent categories was calculated and referenced as the anchor-based CID. Changes in anchors and high disease activity (HDA) shift from baseline to each follow-up visit were then assessed by FACIT-Fatigue score change (≤1 CID, no change, or ≥1 CID). HDA was defined as lactate dehydrogenase ratio ≥1.5 × upper limit of normal and ≥1 of the following: history of a major adverse vascular event (including a thrombotic event); anemia; or physician-reported abdominal pain, dyspnea, dysphagia, fatigue, hemoglobinuria, or erectile dysfunction. Results: 423 patients were included in the analysis (Table). The majority of patients were white or of Caucasian descent (84%); 3% were of Hispanic or Latino ethnicity. At baseline, 93% of patients had physician documentation of fatigue in their medical history (mean FACIT-Fatigue score, 29.4). The 2 distribution-based CIDs were 7 using 0.5 × SD and 5 using SEM; internal consistency was high (α=0.87). For anchor-based measurements, the CID was 8 using the EORTC QoL score and 10 using the EORTC fatigue subscale score. The percentage of patients who changed from having HDA at baseline to no HDA at eculizumab-treated follow-up visits increased over time. Using the SEM as the referent CID (owing to the high α value), the majority of these patients experienced >1 CID in FACIT-Fatigue that was sustained through 36 months (Figure). Results were similar when 0.5 × SD was used. Conclusion: Collectively, these results support the use of 5 points as the CID for FACIT-Fatigue in individual patients with PNH, which, although not necessarily the minimal value, is close to the range of CIDs reported in other diseases (3-5 points). This finding, obtained from a real-world dataset with a large number of patients, helps establish an important metric for assessment of the meaningful treatment response of patients with PNH. Of note, this CID is markedly smaller than the group average FACIT-Fatigue improvement of 10 points achieved with long-term eculizumab treatment in the pivotal blinded Phase 3 TRIUMPH study. Figure 1 Figure 1. Disclosures Cella: FACIT: Membership on an entity's Board of Directors or advisory committees. Ueda: Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Chugai Pharmaceutical: Consultancy, Honoraria, Research Funding; Alexion Pharma: Consultancy, Honoraria. Tomazos: Alexion, AstraZeneca Rare Disease: Current Employment. Gustovic: Alexion, AstraZeneca Rare Disease: Current Employment. Wang: Alexion, AstraZeneca Rare Disease: Current Employment. Patel: Alexion, AstraZeneca Rare Disease: Current Employment. Schrezenmeier: Novartis: Honoraria; Alexion, AstraZeneca Rare Disease: Honoraria, Other: Travel support, Research Funding; Roche: Honoraria; Apellis: Honoraria; Sanofi: Honoraria.

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The Independent Effects of Frailty and Comorbidity On the Quality of Life in MDS Patients

Blood ◽

10.1182/blood.v120.21.699.699 ◽

2012 ◽

Vol 120 (21) ◽

pp. 699-699

Author(s):

Rena Buckstein ◽

Shabbir M.H. Alibhai ◽

Dina Khalaf ◽

Adam Lam ◽

Alex Mamedov ◽

...

Keyword(s):

Quality Of Life ◽

Overall Survival ◽

Health Status ◽

Global Health ◽

Median Time ◽

Research Funding ◽

Global Health Status ◽

Risk Categories ◽

Over Time

Abstract Abstract 699 Background: MDS is a disease of the elderly. While comorbidity defined by the MDS comorbidity index (MDS-CI) may have independent impact on overall survival in MDS (Della Porta MG., Haematologica 2011), the impact of clinical frailty (an age-related vulnerability state created by loss of physiologic reserve) on clinical outcome and quality of life is not yet known. Rockwood and colleagues have developed a simple 9-point clinical frailty scale (CFS) based on clinical judgment that was highly correlated with the risk of death, institutionalization, worsening health and hospital use (Rockwood K., CMAJ 2005). Since 2008, we have prospectively assessed QOL in all patients registered at our MDS clinic using the instruments EORTC QLQ-C30, FACIT-F, and EQ-5D. Since January 2012, we have also recorded comorbidity and frailty. We present longitudinal QOL data on 240 patients and evaluate the effects of comorbidity (MDS-CI) and frailty (CFS) on QOL in addition to the more traditional covariates. Methods: We considered the following co-variates' potential impact on QOL scores: age, sex, IPSS, time from diagnosis, hemoglobin, transfusion dependence, MDS-CI categorically and frailty. We used univariate and multivariate linear regression analysis to determine their relationship with QOL scores at baseline and over time. For time-dependent covariates, linear mixed modelling was used. P value of <0.05 was considered significant. Spearman correlation was calculated between frailty and comorbidity. Clinically significant (CS) score differences were considered 10 points for the EORTC, 0.08 for EQ5-D and 4 for the FACT-Fatigue. Patients provided informed consent for this REB-approved study. Results: 236 patients (63% males) consented at a median time from diagnosis of 0.8 years (IQR 0.4–2.8). The median time to death or last follow-up was 2 years (95% CI 1.9–2.3). At first QOL assessment, the median age was 72 y. Of the 208 patients with measurable IPSS scores, 83% fell into low/low intermediate risk categories. 40% were transfusion dependent, 46% had a Hgb of <100 g/L and 31% had a ferritin >1000 ug/L. Serial QOLs were measured on 2 (n=187 patients), 3 (140), 4 (114), 5 (86), and 6 (63) occasions with a median lag time between QOLs of 17 weeks (IQR 12–26). The MDS-CI risk categories (scores) were Low (0): 46%, Intermediate (1–2): 41% and High (>2): 12%. The median Rockwood Frailty Score was 3 (range: 1–7). Compared to normative data from the general population, MDS patients had SS and CS differences in the following QLQ-C30 scales: worse physical, role, emotional and cognitive functioning, and worse fatigue and global health status. MDS-CI categories were weakly correlated with frailty (r= 0.25, p=.02). As we have previously shown, at baseline, transfusion dependence had significant negative impact on global health state (p=.0036), EQ-5D (p=.0001) and fatigue (p=.0051) scores and lower hemoglobin had negative impacts on fatigue (p=.01) and dyspnea (p<.0001). Patients with higher frailty scores had significantly worse fatigue (p=.001). Most QOL domains and global QOL scores remained stable over time (figure 1). When examined for significant changes over time, lower frailty scores were independently predictive of improved global health status and health utility (p< .0001) while patients with lower comorbidities had decreased levels of fatigue (p=.04) and dyspnea (p=.02) (Table 1). Conclusions: MDS health-related quality of life scores remain surprisingly stable over time. While transfusion dependence is still highly impactful, frailty and comorbidity are independent variables that should be routinely evaluated for their predictive effects on quality of life, drug toxicity and overall survival. Disclosures: Buckstein: Celgene: Honoraria, Research Funding. Wells:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen Ortho: Honoraria, Research Funding; Alexion: Honoraria, Research Funding.

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Correlation between MPN-SAF TSS and EORTC QLQ-C30 Scores in Patients with PV: Data from the Reveal Study

Blood ◽

10.1182/blood-2018-99-112937 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2259-2259 ◽

Cited By ~ 1

Author(s):

Ivy Altomare ◽

Aaron T. Gerds ◽

David Lessen ◽

Philomena Colucci ◽

Shreekant Parasuraman ◽

...

Keyword(s):

Health Status ◽

Global Health ◽

Research Funding ◽

Symptom Burden ◽

Global Health Status ◽

Employment Equity ◽

Eortc Qlq C30 ◽

Equity Ownership ◽

Eortc Qlq

Abstract Introduction Polycythemia vera (PV) is characterized by clonal proliferation of myeloid cells and erythrocytosis. Patients with PV often present with symptoms or develop symptoms that may negatively impact quality of life (QOL). In clinical trials, the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) have both been used to assess symptom burden in patients with PV. This analysis was conducted in patients with PV enrolled in REVEAL, a multicenter, prospective, observational trial, in an attempt to corroborate previous work by Emanuel et al (J Clin Oncol 2012;30:4098), which demonstrated associations between the MPN-SAF TSS and EORTC QLQ-C30. Methods Patients ≥ 18 years of age with PV were enrolled and followed during usual care visits for ≤ 36 months. Patient-reported outcomes, including the MPN-SAF TSS and EORTC QLQ-C30, were collected at enrollment and at approximate 3-month intervals; only the forms completed at the time of enrollment were included in this analysis. MPN-SAF TSS items are scored on a linear analog scale ranging from 0 (absent) to 10 (worst imaginable), and individual symptom scores were added together to calculate a TSS; higher scores represent worse symptom burden. In the EORTC QLQ-C30, 28 questions are scored using a 4-point scale indicating frequency: 1 (not at all), 2 (a little bit), 3 (quite a bit), and 4 (very much); this includes 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Two questions on overall health and QOL are rated on a 1 (very poor) to 7 (excellent) scale. Five multi-item functional scales (physical, role, cognitive, emotional, and social), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), and a multi-item global health status/QOL scale are derived from the 30 questions. Linear transformation to 0-100 was applied to raw scores to obtain scores for each scale or single item. Higher scores for functional scales and global health status represent higher functioning and better health status/QOL, respectively. Higher scores for symptom scales/items represent higher symptom burden. Pearson correlation coefficient was used to assess correlations between MPN-SAF TSS and EORTC QLQ-C30 scales. Results As of data cutoff (April 30, 2018), 2,298 of 2,510 enrolled patients (91.6%) had completed both MPN-SAF TSS and EORTC QLQ-C30 forms at enrollment. Median age was 67 years (range, 22-97 years), 54.0% were male, and 89.7% were Caucasian. Median disease duration at the time of enrollment was 4.1 years. The majority (52.5%) of patients were treated with hydroxyurea (28.7%) or hydroxyurea with phlebotomy (23.8%). The mean MPN-SAF TSS was 18.7 (out of 100) compared to 21.8 reported by Emanuel et al 2012. The 4 symptoms with the highest mean scores were fatigue (3.5), early satiety (2.6), inactivity (2.5), and itching (2.3). The QLQ-C30 mean scores for overall QOL and health were 5.5 and 5.3, respectively. EORTC QLQ-C30 symptom scales were highest for fatigue (29.9), insomnia (28.7), and pain (20.0). Correlation between MPN-SAF TSS and EORTC QLQ-C30 results showed stronger associations between multiple items (Table). Calculated TSS had the strongest association with fatigue (r = 0.72), pain (r = 0.59), cognitive functioning (r = -0.58), and emotional functioning (r = -0.58). Problems with concentration in the MPN-SAF TSS was moderately correlated with cognitive functioning (r = -0.70) in the EORTC QLC-C30. Fatigue assessments were also moderately correlated (r = 0.65) between the MPN-SAF TSS and EORTC QLQ-C30. Conclusions In this analysis of prospectively gathered real-world data, the MPN-SAF TSS results confirm that patients with PV experience a recognizable constellation of symptoms, including fatigue, early satiety, inactivity, and itching. Not surprisingly, PV-related symptoms have a negative impact on QOL. There were moderate correlations (r = 0.5-0.75) between the MPN-SAF TSS and the EORTC QLC-C30 with respect to global health status/QOL, the 5 functional scales, and fatigue, pain, and dyspnea. Consistent with the previous analysis, this analysis provides further evidence that the MPN-SAF TSS represents an accurate, yet simple tool to assess PV-related symptoms and their potential impact on QOL. Disclosures Altomare: Novartis: Consultancy; Incyte: Consultancy; Amgen: Consultancy; Bayer: Consultancy; Genentech: Consultancy; Celgene: Other: Advisory Board Member; Ipsen: Other: Advisory Board Member. Gerds:Celgene: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Lessen:Abbvie: Honoraria; Teva: Honoraria, Speakers Bureau; Incyte: Honoraria, Research Funding, Speakers Bureau; Astellas: Research Funding; Bayer: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Portola: Honoraria, Speakers Bureau; Janssen: Research Funding. Colucci:Incyte: Employment, Equity Ownership. Parasuraman:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Mesa:Pfizer: Research Funding; Incyte Corporation: Research Funding; Gilead: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Celgene: Research Funding; Novartis: Consultancy; UT Health San Antonio - Mays Cancer Center: Employment; CTI Biopharma: Research Funding; Genentech: Research Funding.

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PS01.122: LONG-TERM QUALITY OF LIFE IN PATIENTS AFTER MCKEOWN VERSUS IVOR LEWIS ESOPHAGECTOMY

Diseases of the Esophagus ◽

10.1093/dote/doy089.ps01.122 ◽

2018 ◽

Vol 31 (Supplement_1) ◽

pp. 84-84

Author(s):

Egle Jezerskyte ◽

Suzanne Gisbertz ◽

Mark I Van Berge Henegouwen ◽

Luca Saadeh ◽

Marco Scarpa

Keyword(s):

Quality Of Life ◽

Health Status ◽

Global Health ◽

Cognitive Functioning ◽

Ivor Lewis ◽

Physical Role ◽

Eortc Qlq

Abstract Background Treatment of distal esophageal and gastroesophageal junction (GEJ) cancers is challenging. The therapy for these cancers mainly consist of (neo)adjuvant chemo(radio)therapy and surgery. There are different surgical approaches possible for these patients: transthoracic esophagectomy with a cervical anastomosis (McKeown) or an intrathoracic anastomosis (Ivor Lewis). However, there is no evidence which is the preferred approach in terms of oncology, morbidity and quality of life. The aim of this study was to investigate the difference in the long-term quality of life in patients undergoing McKeown (McK) versus Ivor Lewis (IL) esophagectomy in a tertiary referral center. Methods Consecutive patients after either McK or IL for distal oesophagus, GEJ or proximal gastric carcinoma were asked to fill in EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires to evaluate quality of life during the period of January 2014 – December 2017. EORTC QLQ-INFO25 quality of life questionnaire was used to evaluate information needs of patients in both groups. All answers with a long follow up (> 1 year) after surgery were analysed. Results In the McK group 62 and in the IL group 110 patients were included. Median follow up was 3 years for McK and 2 years for IL. Median age was 62,4 years. Cognitive functioning was significantly better in the IL group (P = 0.038). Complaints of dyspnoe (P = 0.004) and dysphagia (P = 0.028) were significantly higher in the McK group. Patients after IL had significantly less trouble with eating with others (P = 0.003), trouble with taste (P = 0.032), chocking when swallowing (P = 0.022) and trouble with talking (P = 0.038). There was no significant difference in global health status or physical, role, social or emotional functioning. Furthermore there was no difference in symptoms of nausea, fatigue, pain, discomfort or information scores between McK and IL groups. Conclusion After a follow up of > 1 year no differences in global health status or physical, role, social or emotional functioning scales between McK and IL esophagectomy were found. However, significant differences in some symptom scales and cognitive functioning were observed in favor of IL. These findings should be taken into consideration when deciding between a McK and IL esophagectomy in patients where both procedures are feasible. Disclosure All authors have declared no conflicts of interest.

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