Health-Related Quality of Life and Symptoms in Myelofibrosis Patients Treated with Ruxolitinib Versus Best Available Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 795-795
Author(s):  
Claire N. Harrison ◽  
Jean-Jacques Kiladjian ◽  
Haifa Kathrin Al-Ali ◽  
Heinz Gisslinger ◽  
Laurent Knoops ◽  
...  
Keyword(s):  
Research Funding ◽  
Treatment Phase ◽  
Well Being ◽  
Employment Equity ◽  
Advisory Committees ◽  
Eortc Qlq C30 ◽  
Health Related ◽  
Equity Ownership ◽  
Eortc Qlq

Abstract Abstract 795FN2 Background: Ruxolitinib (INC424), a potent and selective oral JAK1 and JAK2 inhibitor, demonstrated rapid and durable reductions in splenomegaly and improved disease-related symptoms, role functioning, and quality of life (QoL) in 2 phase 3 studies in patients with myelofibrosis (MF) (the COMFORT studies). Per-protocol, patient-reported, health-related QoL (HRQoL) and symptoms analyses in the COMFORT-II study are limited. Here we report on additional post hoc analyses of these outcomes. The COMFORT-II study includes 219 patients (ruxolitinib, n=146; best available therapy [BAT], n=73). At entry, all patients were classified into intermediate 2-risk or high-risk prognostic groups (Cervantes F, et al. Blood, 2009;113(13):2895-2901) and had palpable splenomegaly ≥5 cm below the costal margin. Patients could have received prior therapy for MF. On BAT, doses and schedules or no therapy were selected by the investigator; therapy adjustments were permitted during the randomized treatment phase at the investigator's discretion. Patients in both arms continued in the randomized treatment phase as long as there was no protocol-defined disease progression. Methods: The European Organisation for the Research and Treatment of Cancer (EORTC) QoL Questionnaire–Core 30 (QLQ-C30) and Functional Assessment of Cancer Therapy–Lymphoma (FACT-Lym) questionnaires were assessed at baseline and weeks 8, 16, 24, and 48. EORTC QLQ-C30 consists of 30 items combined into 15 subscales (Global Health Status/QoL, 5 functioning subscales, and 9 symptom subscales; scores range from 0 to 100, and higher scores indicate better HRQoL and functioning but a worsening of symptoms). FACT-Lym consists of 42 items combined into 8 subscales (4 well-being subscales; 1 symptom subscale [LymS]; and 3 total scale scores: FACT-General [G], FACT-Lym trial outcome index [TOI], and FACT-Lym total; scores for the different subscales vary from 0–28 to 0–168, and higher scores indicate better outcomes). This analysis includes evaluable patients in the randomized treatment phase and assesses changes from baseline in HRQoL and MF symptom scores, including the EORTC subscales, LymS, and FACT total scores, which incorporate well-being and/or symptom subscales. Mixed-model analyses, adjusted for age, sex, baseline score, and prognostic risk category, are used to evaluate treatment differences at each time point and overall across time. Results: HRQoL and MF symptoms, on average, improved compared with baseline for patients receiving ruxolitinib, but remained the same or worsened for patients receiving BAT. Based on the EORTC QLQ-C30, the treatment differences in physical functioning, role functioning, fatigue, and appetite loss significantly favored ruxolitinib starting at week 8 (P <.05) and remained significant at week 48 (P <.05). The overall between-treatment differences (on average across time) in adjusted mean change from baseline for MF symptom scores (95% confidence interval) were: Fatigue, –10.2 (–15.9, –4.5; P <.001); Dyspnea, –11.6 (–17.6, –5.6; P <.001); Appetite loss, –16.3 (–21.5, –11.1; P <.0001); Insomnia, –9.8 (–16.7, –3.0; P <.01); and Pain, –9.0 (–14.9, –3.0), P <.01); negative values favor ruxolitinib. Global Health Status/QoL (Figure) was significantly improved in the ruxolitinib arm compared with the BAT arm at weeks 8, 16, and 48. Scores on the LymS, which includes symptoms of pain, swelling, fever, night sweats, itching, trouble sleeping, fatigue, weight loss, loss of appetite, trouble concentrating, and other patient concerns, also improved significantly during treatment (Figure). Additionally, FACT-G, FACT-Lym TOI, and FACT-Lym total scores were all significantly (P <.05) improved for patients receiving ruxolitinib treatment compared with BAT. Most EORTC QLQ-C30 and FACT-Lym scores improved significantly on ruxolitinib compared with BAT. The treatment effect between the high-risk and intermediate 2-risk prognostic groups was not significantly different based on an analysis of the risk group–by–treatment interaction. Conclusions: These additional analyses from the COMFORT-II study further support that ruxolitinib significantly improves overall HRQoL and MF symptoms compared with BAT. Disclosures: Harrison: Novartis: Honoraria; Incyte: Honoraria; S*Bio: Honoraria; Celgene: Honoraria; Sanofi Aventis: Honoraria. Kiladjian:Novartis: Honoraria; Celgene: Honoraria. Gisslinger:Novartis: Speakers Bureau; Celgene Austria: Research Funding, Speakers Bureau; Aop-Orphan: Speakers Bureau. Knoops:Novartis: Consultancy. Waltzman:Novartis: Employment. Mendelson:Novartis: Employment, Equity Ownership. Zhou:RTI-HS: Employment; Novartis: Research Funding. Copley-Merriman:RTI-HS: Employment; Novartis: Research Funding. Hunter:Incyte Corporation: Employment, Equity Ownership. Levy:Incyte Corporation: Employment, Equity Ownership. Cervantes:Bristol-Myers-Squibb: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Passamonti:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vannucchi:Novartis: Honoraria. Barosi:Novartis: Consultancy.

Health Related Quality of Life of Bosutinib in Imatinib-Resistant or Imatinib-Intolerant Patients with Advanced Chronic Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4448-4448 ◽  
Author(s):  
Jennifer Whiteley ◽  
Arlene Reisman ◽  
Virginia Kelly ◽  
Jorge E Cortes ◽  
David Cella
Keyword(s):  
Myeloid Leukemia ◽  
Research Funding ◽  
Well Being ◽  
Health Related Quality ◽  
Employment Equity ◽  
Blast Phase ◽  
Related Quality ◽  
Health Related ◽  
Equity Ownership

Abstract Abstract 4448 Purpose: Bosutinib is a dual Src/Abl tyrosine kinase inhibitor (TKI), which has demonstrated efficacy in a phase I/II study of patients with Advanced Phase Chronic Myeloid Leukemia (CML). The objective was to evaluate the effect of bosutinib on health -related quality of life (HRQoL) in patients with advanced CML after failure with imatinib. Methods: Patient reported HRQoL was an exploratory objective in the clinical trial and measured using the 44-item Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu). The FACT-Leu is a modular approach to assess patient HRQoL using a core set of general cancer questions as well as a cancer site specific leukemia subscale with 5 domains: Social Well-being (SWB), Emotional Well-being (EWB), Physical Well-being (PWB), Functional Well-being (FWB) and Leukemia Subscale (LeuS); and 3 summary scales: FACT-General, FACT Trial Outcome Index (TOI) and FACT-Leu Total. The item responses for each scale are summed to provide scores; higher scores indicate better HRQoL. The FACT-Leu was completed at weeks 4, 8, 12 and every 12 weeks thereafter, as well as treatment completion. Within cohort comparisons were assessed using paired t-tests. Results: Of the 164 patients with advanced leukemia included in the trial, 76 had accelerated phase (AP) CML and 64 blast phase (BP) CML. At 24 weeks, AP patients reported statistically significant improvements in PWB (p=0.02), EWB (p<0.001), LeuS (p<0.001), FACT-G (p<0.001), FACT-Leu (p<0.001) and FACT-TOI (p<0.001) with the PWB, FACT-G, LeuS, TOI and FACT-Leu exceeding minimally important differences (MID) at 24 weeks. Blast phase patients reported significant improvements in PWB (p=0.02), EWB (p=0.02), FWB (p=0.04), LeuS (p=0.01), FACT-G (p<0.001), FACT-Leu (p<0.001) and FACT-TOI (p=0.01) at 24-weeks with all scales exceeding MID except the SWB. At 48-weeks the AP patients continued to have statistically significant improvements in PWB (p=0.05), EWB (p=0.02), and FACT-G (p=0.03) and PWB, FACT-G, TOI and FACT-Leu exceeded the MID at 48 weeks. There were no statistically significant deteriorations in HRQoL through week 48 (Figure 1) Conclusions: These data suggest that CML patients treated with bosutinib demonstrate improved HRQoL. Confirmation in a controlled study is needed. Disclosures: Whiteley: Pfizer Inc: Employment, Equity Ownership. Reisman:Pfizer Inc: Employment, Equity Ownership. Kelly:Pfizer Inc: Employment, Equity Ownership. Cortes:Novartis, Bristol Myers Squibb, Pfizer, Ariad, Chemgenex: Consultancy, Research Funding. Cella:Pfizer Inc: Honoraria, Research Funding.

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

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4858-4858 ◽  
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.

scholarly journals Age Subgroup Analysis of Health-Related Quality of Life of Blinatumomab Versus Standard-of-Care Chemotherapy in Patients with Relapsed or Refractory Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia in a Randomized, Open-Label, Phase 3 Study (TOWER)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5165-5165
Author(s):  
Max S. Topp ◽  
Zachary F. Zimmerman ◽  
Paul Cannell ◽  
Hervé Dombret ◽  
Johan Maertens ◽  
...  
Keyword(s):  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Standard Of Care ◽  
Employment Equity ◽  
Phase 3 ◽  
Advisory Committees ◽  
Eortc Qlq C30 ◽  
Equity Ownership ◽  
Eortc Qlq

Abstract Background: Despite the availability of new therapies for acute lymphoblastic leukemia (ALL), older patients have historically poor responses to treatment and poor outcomes versus younger patients, with 5-year survival rates of approximately 20% or less. Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that redirects cytotoxic T cells to lyse CD19-positive B cells and is approved for the treatment of relapsed or refractory (r/r) B-cell precursor (BCP) ALL and for minimal residual disease-positive ALL in the US. In the phase 3 TOWER study in patients with r/r Philadelphia chromosome-negative (Ph-) BCP ALL who received blinatumomab compared with standard-of-care (SOC) chemotherapy, overall survival was improved (median, 7.7 vs 4.0 months; P=0.01; Kantarjian H, et al. N Engl J Med. 2017;376:836-847), and posttreatment health-related quality of life (HRQoL) across all EORTC QLQ-C30 scales was better (Topp MS, et al. Blood. 2018;131:2906-2914). TOWER efficacy results did not differ by age group. In this subgroup analysis of TOWER, we assessed the HRQoL of older patients versus younger patients who received blinatumomab or SOC chemotherapy. Methods: Patients (N=405) with r/r Ph- BCP ALL were randomized 2:1 to receive 2 cycles of induction blinatumomab by continuous intravenous infusion (n=271) or SOC (n=134). Patients could receive transplant at any time following cycle 1. Those in remission could receive up to 3 consolidation cycles; 12 months of maintenance was allowed for those who received up to 3 consolidation cycles and had bone marrow response. HRQoL was assessed using the EORTC QLQ-C30 Questionnaire on days 1 (baseline), 8, and 15, on day 29 of cycle 1; day 1, 15, and 29 of each consolidation cycle; and at the safety follow-up. The questionnaire included 1 global health status scale, 5 functioning scales, 3 symptom scales, and 6 single-symptom items. For global health status and functioning scales, a higher score indicates better HRQoL; for symptom scales/items, a lower score indicates better HRQoL. A 10-point change was viewed as the minimum clinically important difference in EORTC QLQ-C30 (Zikos E, et al. EORTC. 2016). In this analysis, HRQoL in TOWER was assessed using two different age cutoffs: <35 versus ≥35 years (the randomization stratification in TOWER) and <55 versus ≥55 years (the stratification factor for INO-VATE, a phase 3 trial for another therapy in r/r ALL). Analyses included patients with baseline and ≥1 postbaseline result of any multi-item scale or single-item measure. Mean change from baseline in scores for each scale/item were summarized for cycle 1. Time to deterioration (TTD) analyses assessed the treatment effect based on timing from the initiation of treatment to a ≥10-point decrease for the functional scales and/or a ≥10-point increase for the symptom scales respectively. Conclusions: Consistent with the efficacy results, compared with SOC, blinatumomab improved HRQoL and delayed the deterioration in HRQoL regardless of the age group in patients with r/r Ph- BCP ALL. Disclosures Topp: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Boehringer Ingelheim: Research Funding; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding. Zimmerman:Amgen Inc.: Employment, Equity Ownership. Dombret:Cellectis: Consultancy, Honoraria, Other: Travel expenses; Servier: Consultancy, Honoraria; Immunogen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Ambit (Daiichi Sankyo): Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Menarini: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Shire-Baxalta: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharma: Consultancy, Honoraria, Research Funding; Ariad (Incyte): Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; Roche/Genentech: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau. Stein:Celgene: Speakers Bureau; Amgen Inc.: Speakers Bureau. Franklin:Amgen Inc.: Employment, Equity Ownership. Cong:Amgen, Inc.: Employment, Equity Ownership. Zhang:Amgen Inc.: Employment, Equity Ownership. Schuh:Amgen Inc.: Consultancy; Pfizer: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Otsuka: Consultancy; Shire: Consultancy; Teva: Consultancy; Jazz: Consultancy.

Relationship Between Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) and Efficacy in Patients with Myelofibrosis in the Phase III Persist-1 Trial of Pacritinib Vs. Best Available Therapy (BAT)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1609-1609
Author(s):  
Ruben A. Mesa ◽  
Claire N. Harrison ◽  
Francisco Cervantes ◽  
James P. Dean ◽  
Lixia Wang ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Off Label Use ◽  
Employment Equity ◽  
Advisory Committees ◽  
Off Label ◽  
Eortc Qlq C30 ◽  
Night Sweats ◽  
Equity Ownership ◽  
Eortc Qlq

Abstract Introduction: Myelofibrosis (MF) is a life-threatening hematologic malignancy characterized by splenomegaly and debilitating symptoms including fatigue, abdominal pain, night sweats, bone pain, pruritus, and unintentional weight loss. The myeloproliferative neoplasm symptom assessment form (MPN-SAF) is a PRO tool designed to measure MF-related symptom burden and was developed and validated at Mayo Clinic. It was modified (MPN-SAF total symptom score [TSS] and TSS 2.0) for use in the PERSIST-1 and PERSIST-2 phase 3 trials. For PERSIST-1, when examining the 6 common symptoms in both TSS versions (tiredness, night sweats, early satiety, itchiness, bone pain, and abdominal pain), pacritinib-treated patients (pts) had significant improvements in TSS overall and in individual symptoms vs BAT; Pt Global Impression of Change (PGIC) was also significantly improved for pts receiving pacritinib. Improvements in EORTC-QLQ-C30 scales were noted in the pacritinib arm (Mesa, EHA 2015). The proportion of pts achieving spleen volume reduction (SVR) ≥35% at Week 24 was significantly greater with pacritinib vs BAT (ITT: 19.1% vs 4.7%, p=0.0003; evaluable at baseline and Week 24: 25.0% vs 5.9%; p=0.0001). This analysis examines relationships between TSS improvement and changes in splenomegaly and HRQoL outcomes. Methods: Pts who received no prior JAK inhibitor therapy were randomized 2:1 to oral pacritinib 400 mg once daily or BAT. Pts were stratified by DIPSS risk (Int-1/Int-2 vs High) and platelet count (<50,000/μL vs 50,000/μL to <100,000/μL vs ≥100,000/μL). Pts must have had a baseline total TSS ≥13 using MPN-SAF TSS 2.0. Each symptom is rated on a scale from 0 (absent) to 10 (worst imaginable) using MPN-SAF TSS and TSS 2.0. Results for the 6 symptoms common to both TSS versions are reported. Additional PROs used for assessment of HRQoL included EORTC QLQ-C30 and EQ-5D-5L. In multivariate logistic regressions, odds of TSS reduction ≥50% at Week 24 were modeled as a function of Week 24 SVR ≥35%, spleen length reduction (SLR) ≥ 50%, PGIC, improvement in each EORTC scale, and improvement in EQ-5D-5L Overall Health State (OHS) and in each dimension individually while adjusting for treatment (pacritinib vs BAT). Correlations were examined in all pts and by baseline platelet counts (<50,000/μL, <100,000/μL, and ≥100,000/μL). Results: A total of 327 pts were enrolled (PAC: 220, BAT: 107). 62% of pts had primary MF, 32% had baseline platelets <100,000/μL, and 16% had baseline platelets <50,000/μL. TSS reduction ≥50% was found to be associated with SVR ≥35% and improvement in splenomegaly (SLR ≥50%). In the total pt population, there was a significant association between TSS reduction and SVR (odds ratio [OR]=2.60, p=0.016). In all pts, there was a significant association between TSS reduction and improvements in OHS as measured by EQ-5D-5L (OR=2.30, p=0.013). TSS reductions were also marginally associated with improvements in the QLQ-C30 Global Health Scale (GHS)/QoL Scale (OR=1.92, p=0.050) and, though not statistically significant, there was a trend of improvement in perceived overall health as measured by PGIC (OR=2.16, p=0.118). TSS reductions were further examined in pts grouped by baseline platelet count. Improvement in EQ-5D-5L OHS was marginally associated with TSS reductions in pts with platelets <50,000/μL (OR=6.03, p=0.057). For pts with platelets <100,000/μL, reductions in TSS were significantly associated with reductions in splenomegaly (SLR ≥50%; OR=9.53, p=0.004), and improvements in the QLQ-C30 GHS/QoL domain (OR=4.03, p=0.022) as well as the EQ-5D-5L OHS (OR=5.49, p=0.008). A significant association between TSS reductions and SVR ≥35% was observed in pts with platelets ≥100,000/μL (OR=3.99, p=0.005). In all pts, improvements in Fatigue as measured by QLQ-C30 were significantly associated with TSS reductions (OR=2.20, p=0.019) as well as in pts with baseline platelets <50,000/μL (OR=17.88, p=0.008) and <100,000/μL (OR=10.18, p<0.001). Conclusions: In the total pt population, TSS reduction was associated with improvements in spleen response and perceived overall health. This trend was also observed in pts with low baseline platelet counts. Additionally, TSS reduction was significantly associated with improvements in fatigue, a major contributor to poor HRQoL in pts with MF. This reinforces the clinical relevance of measuring TSS using a validated instrument as an endpoint in MF trials. Disclosures Mesa: NS Pharma: Research Funding; Pfizer: Research Funding; Gilead: Research Funding; Incyte Corporation: Research Funding; CTI Biopharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Genentech: Research Funding; Promedior: Research Funding. Off Label Use: This abstract discusses off-label use of pacritinib. Harrison:Shire: Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Gilead: Honoraria; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau. Cervantes:Novartis: Consultancy, Speakers Bureau; Sanofi-Aventis: Consultancy; CTI-Baxter: Consultancy, Speakers Bureau. Dean:CTI Biopharma: Employment, Equity Ownership. Wang:CTI Biopharma: Employment, Equity Ownership. Yang:Baxalta: Employment, Other: Stock. Vannucchi:Shire: Speakers Bureau; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees.

Changes in Quality of Life and Disease-Related Symptoms in Patients with Polycythemia Vera Receiving Ruxolitinib or Best Available Therapy: RESPONSE Trial Results

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 709-709
Author(s):  
Ruben Mesa ◽  
Srdan Verstovsek ◽  
Jean-Jacques Kiladjian ◽  
Martin Griesshammer ◽  
Tamas Masszi ◽  
...  
Keyword(s):  
Global Health ◽  
Board Of Directors ◽  
Research Funding ◽  
Symptom Burden ◽  
Global Health Status ◽  
Employment Equity ◽  
Advisory Committees ◽  
Eortc Qlq C30 ◽  
Equity Ownership ◽  
Eortc Qlq

Abstract Background : Polycythemia vera (PV) is a myeloproliferative neoplasm driven by JAK/STAT activation and is associated with erythrocytosis and a broad symptom burden that may negatively impact patient quality of life (QoL). Hydroxyurea (HU) is often used as first-line therapy for high-risk patients but may not effectively control or reduce symptom burden. RESPONSE is a phase III trial comparing ruxolitinib (RUX) with best available therapy (BAT) in patients with PV who were intolerant of or resistant to HU according to modified European LeukemiaNet (ELN) criteria. The primary study endpoint (a composite of hematocrit control and ≥35% spleen volume reduction at Week 32) was achieved by 21% of patients in the RUX arm vs 1% in the BAT arm (P<0.0001); 77% of patients in the RUX arm achieved at least one component of the primary endpoint. The current analysis was conducted to evaluate the effect of RUX on PV-related symptoms and QoL measures in the RESPONSE trial. Methods : Patients with PV aged ≥18 years, resistant to or intolerant of HU (modified ELN criteria) with splenomegaly, and who required phlebotomy for hematocrit control were randomized 1:1 to receive open-label RUX 10 mg twice daily (BID) or BAT (administered based on investigator judgment). Dose adjustments were permitted (RUX, 5-mg BID increments [25 mg BID max]; BAT was adjusted per investigator judgment). Objectives of this analysis included assessment of improvement in symptom burden as assessed by patient-reported outcomes using the 14-item modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and the Patient Global Impression of Change. The 14-item MPN-SAF (graded from 0 [absent] to 10 [worst imaginable]) comprised symptoms related to cytokines (tiredness, itching, muscle ache, night sweats, and sweats while awake), hyperviscosity (vision problems, dizziness, concentration problems, headache, numbness/tingling, ringing in ears, and skin redness), and splenomegaly (abdominal discomfort and early satiety). Changes in total symptom score (TSS; maximum score = 140) and individual symptom scores from baseline to Week 32 were summarized by treatment group. For the EORTC QLQ-C30 Global Health Status/QOL score, the percentage of patients with a minimally important difference (MID) from baseline (10-point change) at Week 32 was summarized. Results : Overall, 222 patients were randomized (RUX, 110; BAT, 112). Median age (range) was similar between arms (RUX, 62.0 [34.0–90.0]; BAT, 60.0 [33.0–84.0]); the RUX and BAT arms were 60% and 71% male, respectively. At Week 32, a higher proportion of patients in the RUX vs the BAT arms had a ≥50% improvement in MPN-SAF TSS (49% vs 5%, respectively) and MPN-SAF symptom cluster scores (cytokine, 64% vs 11%; hyperviscosity, 37% vs 13%; splenomegaly, 62% vs 17%). Median percentage changes in individual symptom scores are presented in the Table. Mean changes from baseline at Week 32 on the 5 items of the PSIS indicated that the severity of pruritus and its interference on daily life improved with RUX (range, −1.5 to −2.2) and was unchanged/worsened with BAT (range, −0.1 to 0.3). Treatment with RUX vs BAT was associated with improved mean changes from baseline at Week 32 on EORTC QLQ-C30 symptom subscales, functional subscales, and Global Health Status/QOL (Table); 46% of RUX patients versus 10% of BAT patients achieved an MID in Global Health Status/QOL (Figure). At Week 32, RUX patients were more likely to rate their global impression of symptom changes as “very much improved” or “much improved” (67%) vs BAT patients (13%). Conclusion : In patients with PV who were resistant to or intolerant of HU, treatment with RUX was associated with greater and clinically meaningful improvements in PV-related symptom burden and QoL measures compared with BAT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Mesa: Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Off Label Use: Ruxolitinib is a JAK1/JAK2 inhibitor approved for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Verstovsek:Incyte Corporation: Research Funding. Kiladjian:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Masszi:Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Durrant:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. He:Incyte Corporation: Employment, Equity Ownership. Jones:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Li:Novartis Pharmaceuticals: Employment, Equity Ownership. Côté:Novartis Pharmaceuticals: Employment, Equity Ownership. Habr:Novartis Pharmaceuticals: Employment, Equity Ownership. Vannucchi:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2259-2259 ◽  
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.

scholarly journals Quality of Life in Patients with β-Thalassemia: Transfusion Dependent Versus Non-Transfusion Dependent

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 751-751
Author(s):  
Maria Domenica Cappellini ◽  
Antonis Kattamis ◽  
Vip Viprakasit ◽  
Pranee Sutcharitchan ◽  
Dalia Mahmoud ◽  
...  
Keyword(s):  
Research Funding ◽  
Care Setting ◽  
Clinical Care ◽  
Well Being ◽  
Study Entry ◽  
Employment Equity ◽  
Advisory Committees ◽  
Routine Clinical Care ◽  
Equity Ownership

Abstract Background: Significant increase in life expectancy has been observed in patients with β-thalassemia in recent years. The improved survival, however, is accompanied by significant ongoing healthcare needs related to the chronic condition; therefore, quality of life (QoL) has emerged as a fundamental focus of comprehensive patient care. We compared QoL outcomes between transfusion-dependent (TD) and non-transfusion-dependent (NTD) patients with β-thalassemia in the routine clinical care setting. Method: Adult patients with β-thalassemia were prospectively enrolled in an observational study in Italy, Greece, Lebanon, and Thailand. All patients completed Short Form 36 Health Survey version 2 (SF-36v2) and Functional Assessment of Cancer Therapy (FACT)-Anemia (An) questionnaires at baseline, and then once every 3 weeks using a hand-held electronic device. This analysis evaluated QoL between TD and NTD patients at study entry. Transfusion dependent was defined as receiving ≥ 6 red blood cell (RBC) units in the 24 weeks prior to study entry and no transfusion-free period for ≥ 35 days during that period. Results: A total of 102 patients with β-thalassemia were enrolled, of which 52 were TD and 50 NTD. The mean age of patients was 31.2 years and 70 (68.6%) were females. On average, patients with TD β-thalassemia were 3.6 years younger (P= 0.06) and had moderately higher hemoglobin values at baseline (8.8 vs 8.2 g/dL; P= 0.02). At study entry, all (100%) patients with TD β-thalassemia had received RBC transfusions within the 24 weeks prior to study entry, as per inclusion criteria, versus 5 (10%) patients with NTD β-thalassemia who had received RBC transfusions during the same time period. Patients with NTD β-thalassemia reported lower QoL on all domains and summary scores as captured by the SF-36v2 questionnaire, except for Role-Physical. On average, patients with NTD β-thalassemia experienced statistically significant lower QoL versus their TD counterparts on the domains of General Health (39.5 vs 44.0; P= 0.01), Vitality (49.3 vs 53.7; P= 0.01), and Mental Health (46.8 vs 50.8; P= 0.01), and in the Mental Component Summary Score (46.5 vs 50.8; P= 0.01). Similarly, patients with NTD β-thalassemia reported worse QoL scores from the FACT-An questionnaire on all domains and statistically significant differences were observed for Emotional Well-Being (18.5 vs 20.0; P= 0.02), Functional Well-Being (20.0 vs 23.2; P &lt; 0.01), and FACT-General (82.9 vs 89.4; P= 0.01). Conclusions: In the routine clinical care setting, there are critical unmet medical needs for patients with NTD β-thalassemia as they experience worse QoL on many domains compared with patients with TD β-thalassemia. There is a need for new interventions to treat patients with NTD β-thalassemia and reduce their burden of disease. Disclosures Cappellini: Vifor: Honoraria; Novartis: Speakers Bureau; Celgene: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding, Speakers Bureau. Kattamis: National and Kapodistrian University of Athens: Employment; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy. Viprakasit: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Siriraj Hospital: Employment; Shire: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding. Sutcharitchan: Celgene: Research Funding; Chulalongkorn University: Consultancy, Employment. Mahmoud: Celgene: Employment. Pariseau: Celgene: Employment. Laadem: Celgene: Employment, Equity Ownership. Khan: Nathan S. Kline Institute for Psychiatric Research; Manhattan Psychiatric Center: Employment. Hu: Celgene: Employment, Equity Ownership. Taher: Novartis Pharmaceuticals: Honoraria, Research Funding; Celgene: Research Funding.

Self-Reported Quality-of-Life Impairment and Productivity Loss in Patients with Polycythemia Vera: Early Patient-Reported Outcomes Assessment from the REVEAL Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4084-4084
Author(s):  
Ruben A. Mesa ◽  
Ralph V. Boccia ◽  
Alison Moliterno ◽  
Ahmad B. Naim ◽  
Joseph A. Cordaro ◽  
...  
Keyword(s):  
Research Funding ◽  
Productivity Loss ◽  
Work Productivity ◽  
Employment Equity ◽  
Patient Reported ◽  
Symptom Scores ◽  
Eortc Qlq C30 ◽  
Equity Ownership ◽  
Eortc Qlq

Abstract Background: Patients with polycythemia vera (PV) can have a pronounced symptom burden that negatively impacts their quality of life (QoL). Traditional treatment options such as phlebotomy, hydroxyurea, and interferon provide clinical benefit but frequently do not alleviate symptoms. The ongoing REVEAL study is being conducted to describe contemporary demographics, burden of disease, clinical management, patient-reported outcomes, and healthcare resource utilization among patients with PV in the US. This preliminary analysis describes the burden of PV based on patient-reported outcomes (PROs), including health-related QoL and work productivity. Methods: REVEAL is a multicenter, noninterventional, nonrandomized, prospective, observational study. Eligible patients are ≥18 years of age with a PV diagnosis and currently under active management by a physician in the US. PROs are being collected at study enrollment and every 3 months thereafter. Each of the 10 items on the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) are graded from 0 (absent) to 10 (worst imaginable), with individual symptom scores ≥7 considered severe; total symptom score (TSS) ranges from 0-100. Raw scores for items on the 30-item European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) are standardized by linear transformation to 0-100. Higher scores on the EORTC QLQ-C30 indicate better functioning for global health status/QoL and functional subscales and worse severity for symptom subscales. Outcomes with the 6-item Work Productivity and Activity Impairment Specific Health Problem questionnaire (WPAI-SHP) are presented as a proportion from 0% (minimal/no impairment) to 100% (maximal impairment/productivity loss). Analyses of these preliminary data were descriptive. Results: At the time of data cutoff (June 9, 2015), REVEAL had enrolled 865 patients (total planned enrollment, n=2000), the majority were male (55.5%) and white (89.5%), with a median age of 67 (range, 22-95) years. 782 patients had completed the PRO questionnaires at the enrollment visit. A majority of patients reported ≥1 PV-related symptom. Mean (SD) MPN-SAF symptom scores were highest for fatigue (3.5 [2.7]), early satiety (2.7 [2.8]), inactivity (2.7 [2.9]), itching (2.6 [3.1]), and concentration problems (2.1 [2.6]). The mean (SD) MPN-SAF TSS (sum of 10 symptom scores) was 19.6 (16.1). The most frequently reported severe symptoms were fatigue, itching, inactivity, early satiety, night sweats, concentration problems, and bone pain (Table 1). Mean (SD) global health status/QoL reported on the EORTC QLQ-C30 was 72.8 (23.4); functional subscales were as follows: cognitive functioning, 80.3 (24.5); emotional functioning, 80.7 (24.0); physical functioning, 83.1 (20.6); role functioning, 84.3 (26.1); and social functioning, 85.0 (25.0). The most severe mean (SD) symptom subscale scores were fatigue (30.7 [28.5]), insomnia (29.5 [34.5]), pain (20.9 [29.3]), and dyspnea (17.3 [28.6]). Among patients who were employed at baseline (n=273), mean (SD) PV-related WPAI-SHP scores were as follows: absenteeism (ie, work time missed), 2.9% (10.6%); presenteeism (ie, impairment at work/reduced on-the-job effectiveness), 10.7% (20.4%); work productivity loss (ie, absenteeism plus presenteeism), 12.0% (22.2%); and activity impairment, 21.0% (28.0%). Conclusion: Preliminary descriptive data from patients currently enrolled in REVEAL suggest that patients with PV have notable impairment in QoL because of their disease; patient-reported scores on the MPN-SAF and EORTC QLQ-C30 were similar to those reported previously for patient populations with MPNs. Similarly, PV is associated with marked work productivity loss among patients who are currently employed. Subsequent analyses from REVEAL will evaluate changes over time in PROs and investigate correlations with disease progression and treatment. REVEAL can provide novel insights into questions related to the contemporary real-world QoL burden and its impact on PV-related symptoms and work productivity. Disclosures Mesa: Pfizer: Research Funding; NS Pharma: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Incyte Corporation: Research Funding; CTI Biopharma: Research Funding; Promedior: Research Funding. Boccia:Incyte Corporation: Honoraria. Moliterno:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Naim:Incyte Corporation: Employment, Equity Ownership. Cordaro:Incyte Corporation: Employment, Equity Ownership. Peng:Incyte Corporation: Employment, Equity Ownership. Sun:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Stein:Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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

Blood ◽  
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.

Phase II Study of the Pan-Deacetylase Inhibitor Panobinostat in Combination with Bortezomib and Dexamethasone in Relapsed and Bortezomib-Refractory Multiple Myeloma (PANORAMA 2)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 814-814 ◽  
Author(s):  
Paul G. Richardson ◽  
Melissa Alsina ◽  
Donna M. Weber ◽  
Steven E. Coutre ◽  
Sagar Lonial ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Phase 1 ◽  
Treatment Phase ◽  
Employment Equity ◽  
Advisory Committees ◽  
Overall Response ◽  
Equity Ownership ◽  
Grade 3 ◽  
Stage 1

Abstract Abstract 814FN2 Background: Patients with refractory multiple myeloma (MM) have limited treatment options and an extremely poor prognosis. A recent study of patients who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive an immunomodulatory drug (IMiD, thalidomide or lenalidomide) demonstrated a median event-free survival of only 5 months (Kumar S et al, Leukemia, 2011). Panobinostat is an oral pan-deacetylase inhibitor (pan-DACi) that increases acetylation of proteins involved in multiple oncogenic pathways. Preclinical studies have demonstrated synergistic anti-myeloma activity of the combination of panobinostat and bortezomib through dual inhibition of the aggresome and proteasome pathways. In a phase I study (B2207) of patients with relapsed or relapsed/refractory MM treated with panobinostat + bortezomib, clinical responses (≥ minimal response [MR]) were observed in 65% of patients, including in patients with bortezomib-refractory disease. PANORAMA 2 seeks to expand upon these preliminary results and seeks to determine whether panobinostat can sensitize resistant patients to a bortezomib-containing therapeutic regimen. Methods: PANORAMA 2 is a single arm, phase II study of panobinostat + bortezomib + dexamethasone in patients with bortezomib-refractory MM. Patients with relapsed and bortezomib-refractory MM (≥ 2 prior lines of therapy including an IMiD and who had progressed on or within 60 days of the last bortezomib-based therapy) are treated in 2 phases. Treatment phase 1 consists of 8 three-week cycles of oral panobinostat (20 mg days 1, 3, 5, 8, 10, 12) + intravenous bortezomib (1.3 mg/m2 days 1, 4, 8, 11) + oral dexamethasone (20 mg on day of and after bortezomib). Patients demonstrating clinical benefit (≥ stable disease) can proceed to treatment phase 2, consisting of 4 six-week cycles of panobinostat (20 mg TIW 2 weeks on 1 week off, and repeat) + bortezomib (1.3 mg/m2 days 1, 8, 22, 29) + dexamethasone (20 mg on day of and after bortezomib). The primary endpoint is overall response (≥ partial response [PR]), as defined by the European Group of Blood and Marrow Transplantation 1998 criteria, in the first 8 cycles of treatment phase 1. A Simon 2-stage design is used to test the primary endpoint where ≥ 4 responses (≥ PR) in 24 patients are needed in stage 1 in order to proceed to stage 2, where ≥ 9 responses in all patients (N = 47) are required to reject the null hypothesis (overall response rate ≤ 10%). Results: A sufficient number of responses ≥ PR were observed in stage 1 to allow for enrollment to continue to stage 2. As of 15 July 2011, 53 patients with bortezomib-refractory MM were enrolled. Safety and demographic data were available for 48 patients. The median age was 61 (41–88) years. Patients were heavily pretreated, with a median of 4 (2–14) prior regimens, and most patients (69%) received prior autologous stem cell transplant. Efficacy data were available for 44 patients. At the time of this analysis, 9 patients achieved ≥ PR (2 near CR [nCR] and 7 PR) as best overall response, and an additional 7 patients achieved an MR. Responders exhibited a long duration on therapy, and, to date, 8 patients have proceeded to treatment phase 2. The 2 patients with nCR have received ≥ 10 cycles of treatment (duration of therapy 190 and 253 days). Four patients who achieved PR have received ≥ 9 cycles (duration of therapy 155–225 days). Updated response data will be presented. Common adverse events (AEs) of any grade included, fatigue (52%), diarrhea (41%), thrombocytopenia (38%), nausea (38%), and anemia (21%). Gastrointestinal AEs were generally mild, with a relatively low incidence of grade 3/4 events. Grade 3/4 AEs were generally hematologic in nature, with grade 3/4 thrombocytopenia, anemia, and neutropenia reported in 38%, 12%, and 10% of patients, respectively. Other common nonhematologic grade 3/4 AEs included fatigue (10%) and pneumonia (10%). Of note, to date, a relatively low rate of peripheral neuropathy (17%) has been observed. No grade 3/4 peripheral neuropathy has been observed. Conclusions: The combination of panobinostat and bortezomib is a promising treatment for patients with bortezomib-refractory MM. These data, along with forthcoming data from the phase III study of panobinostat/placebo + bortezomib + dexamethasone in patients with relapsed MM (PANORAMA 1), will further define the potential role of panobinostat in the treatment of patients with MM. Disclosures: Richardson: Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Alsina:Novartis: Research Funding; Celgene: Research Funding; Ortho Biotech: Research Funding; Onyx: Research Funding; Millennium: Consultancy, Research Funding. Weber:Millennium: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Research Funding. Lonial:Millennium: Consultancy; Celgene: Consultancy; Merck: Consultancy; Onyx: Consultancy; BMS: Consultancy; Novartis: Consultancy. Gasparetto:Millennium: Speakers Bureau. Warsi:Novartis: Employment, Equity Ownership. Ondovik:Novartis: Employment, Equity Ownership. Mukhopadhyay:Novartis: Employment, Equity Ownership. Snodgrass:Novartis: Employment, Equity Ownership.

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