Patient-Reported Quality of Life (QoL) in Elderly, Newly Diagnosed Multiple Myeloma (MM) Patients Receiving Bortezomib-Based Combinations: Results From All Randomized Patients in the Community-Based, Phase 3b UPFRONT Study

Abstract Abstract 1864 Background: In addition to determining the efficacy and safety of different treatment options for MM, the impact of treatment and associated toxicities on patient-reported QoL should be evaluated. The US community-based phase 3b UPFRONT study compares the efficacy and safety of three bortezomib (VELCADE®, Vc)-based regimens, Vc-dexamethasone (VcD), Vc-thalidomide-dexamethasone (VcTD), and Vc-melphalan-prednisone (VcMP), followed by weekly Vc maintenance, in elderly, newly diagnosed, transplant-ineligible MM patients. Updated efficacy and safety data are reported elsewhere at this meeting; here we present patient-reported QoL results – a secondary endpoint of the trial – from all 502 randomized patients, who received up to a maximum of 13 treatment cycles. Methods: Patients with symptomatic MM were randomized (1:1:1) to receive eight 21-day cycles of VcD (Vc 1.3 mg/m2, days 1, 4, 8, 11; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [cycles 1–4]), days 1, 2, 4, 5 [cycles 5–8]), VcTD (Vc as before; T 100 mg/day, days 1–21; D as before), or VcMP (Vc as before; M 9 mg/m2, and P 60 mg/m2, days 1–4, every other cycle) induction, followed by five 35-day cycles of maintenance with Vc 1.6 mg/m2, days 1, 8, 15, 22. QoL was assessed using the EORTC QLQ-C30 questionnaire, which includes global health status, physical, role, cognitive, emotional, and social functioning, and symptom scales of fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Global health status scores combine overall health and QoL scores, with higher scores reflecting better health status. Questionnaires were completed prior to dosing on day 1 of cycle 1 (baseline), prior to dosing on day 1 of every odd-numbered cycle, at the end-of-treatment visit, and every 12 weeks until progressive disease. Patient-reported QoL scores presented herein represent data collected within 1 year of randomization regardless of discontinuation status; for patients who died, missing assessments were assigned the worst possible score of 0. A linear mixed effect model was used to assess QoL changes over time, both within and between treatment arms. Sensitivity analyses were conducted to test the robustness of the primary analysis. Results: Patient baseline characteristics were well balanced across the VcD (n=168), VcTD (n=167), and VcMP (n=167) arms as reported previously (Niesvizky et al, EHA 2011). Median age was 74.5 (VcD), 73.0 (VcTD), and 72.0 (VcMP) years, and 71%, 62%, and 72% of patients had ISS stage II/III disease. QoL assessments were available at baseline and ≥1 post-baseline time point for 78% (VcD), 69% (VcTD), and 78% (VcMP) of patients. Observed data showed a downward trend in mean global health status score until cycle 7 (VcD, VcMP) or 9 (VcTD), followed by a trend to stabilizing/improving score thereafter (Figure). Symptom scores changed very little during induction in all arms, except for nausea/vomiting and diarrhea, with moderate improvements seen during maintenance. After fitting observed data with a linear mixed effect model, a significant decrease in mean global health status score from baseline to cycle 7 (induction period) was evident in all arms (VcD, p=0.0127; VcTD, p<0.0001; VcMP, p=0.0157), but there were no significant inter-arm differences. During cycles 9–13 (maintenance period), mean global health status scores remained decreased from baseline in the VcD and VcTD arms, and there were significant differences between VcTD and VcMP, with lower scores in the VcTD arm. Sensitivity analyses incorporating patients' QoL data collected after discontinuation of treatment (for patients who discontinued within 1 year) and utilizing a last observation carried forward approach, gave similar results to the linear mixed effect model. Conclusions: The observed data, linear mixed model estimates, and sensitivity analyses all show a common trend to a transient decrease in QoL during VcD, VcTD, and VcMP induction followed by a subsequent trend to improvement/stabilization in QoL during single-agent Vc maintenance. The trend to decreasing QoL seen during Vc-based induction may reflect the onset of treatment-related toxicities (particularly for VcTD, which was associated with somewhat higher toxicity rates). Post-induction improvements/stabilization in QoL may reflect the beneficial impact of achieving a response and the limited toxicity profile associated with weekly Vc maintenance. Disclosures: Niesvizky: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Research Funding. Flinn:Millennium Pharmaceuticals, Inc.: Research Funding. Rifkin:Onyx: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Millennium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Charu:Pfizer: Equity Ownership; Bristol-Myers Squibb: Equity Ownership; Roche: Research Funding; GSK: Research Funding; Celgene: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Neuwirth:Millennium Pharmaceuticals, Inc.: Employment. Huang:Millennium Pharmaceuticals, Inc: Employment. Choi:Millennium Pharmaceuticals, Inc.: Employment. Corzo:Millennium Pharmaceuticals, Inc.: Employment.

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The Effects of Azacitidine On Quality of Life: A Prospective Longitudinal Assessment

Blood ◽

10.1182/blood.v120.21.4938.4938 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4938-4938

Author(s):

Eric Tseng ◽

Richard A. Wells ◽

Shabbir MH Alibhai ◽

Adam Lam ◽

Alex Mamedov ◽

...

Keyword(s):

Health Status ◽

Global Health ◽

Board Of Directors ◽

Median Time ◽

Research Funding ◽

Global Health Status ◽

Advisory Committees ◽

Over Time

Abstract Abstract 4938 The effect of azacitidine (AZA) on health related quality of life (QOL) compared with best supportive care in MDS patients has been evaluated by Kornblith A. et al (JCO 2002) in a prospective randomized CALGB trial. The study demonstrated improved fatigue, dyspnea, physical functioning and psychological state in patients receiving AZA. One limitation is the relatively short follow up (last QOL measured at 8. 6 months) and the lack of validation in a non-trial setting. We have been conducting prospective assessments of QOL in all patients registered at our MDS clinic using the instruments EORTC QLQ-C30, FACT-Fatigue, EQ-5D and a global fatigue scale. We present longitudinal data on 56 registered patients registered in our program who were treated with AZA, 50 with serial QOLs. Methods: We examined and compared QOL scores at AZA start (baseline) and over time in all patients. We considered the following co-variates' potential impact on QOL scores: age, sex, IPSS, time from diagnosis, being a responder, # cycles and transfusion dependence. We used univariate linear regression analysis for continuous variables and analysis of variance (ANOVA) for categorical variables to determine their relationship with QOL scores at baseline and over time. For time-dependent covariates, linear mixed model was performed with random intercept and unstructured covariance matrix. Clinically significant (CS) score differences were considered 10 points for the QLQ-C30, 4 for the FACT-Fatigue and 0. 08 for the EQ-5D (7 for the visual analog score). The impact of baseline covariates on the QOL scores for global health, fatigue and dyspnea were determined by backward selection procedure of regression analysis using the Bonferroni adjusted P value of <0. 01 for multiple comparisons. Patients provided informed consent for this REB approved study. Results: 56 MDS patients consented to our registry have been treated with AZA between Oct 2008 and July 2012. The median age was 72, 60% were male and 77% had int-2/high risk IPSS MDS. 64 % were transfusion dependent (TD) at baseline. With a median time to death or last follow up of 16 months (range 1. 5–45) a median of 11 cycles of AZA were administered with 34% remaining on drug for a median of 25 cycles (IQR 8–32). The overall response rate (ORR) was 62%: 25% CR; 5% MCR; 4% PR; 28% HI. Stable disease (SD) was seen in 26% and not considered a response. 53% became transfusion independent (TI). 59% have died and 61% developed leukemia or progressed to > 30% blasts at a median time of 13 months. Overall survival was 18 months (95% CI 14. 5–26). 50 were evaluable for HrQOL with a median time between each serial QOL of 13 weeks (IQR 10–18). QOL was assessed at baseline (within 12 weeks pre-AZA start) in 50 patients, 2x in 44, 3x in 32, 4x in 22 and 5x in 14 patients (exceeding 52 weeks follow up). Looking at all 50 patients, overall, function and symptom domains remained stable over time in all instruments. At baseline, there were no statistically significant differences in QOL scores between responders and non responders. Nevertheless, clinically important differences were seen in physical, role, cognitive and social functioning, global health status (all higher in responders). Assessing QOL changes over time and considering baseline and time-dependent predictive factors in multivariate analysis, responders had significantly superior global health status (p=. 001) and EQ-5D scores (p=. 0002) and lower levels of fatigue (p<. 0001). If transfusion dependence status at time of QOL was included in the model, this often supplanted response as predictive of higher scores over time, likely representing the strong relationship between response and transfusion dependence. Conclusions: In addition to validating the clinical outcomes of AZA-001 study, we validate the importance of clinical response on QOL in MDS patients treated with AZA. Unlike the CALGB study, we observed relative stability in global health status and fatigue scores in responding patients and overall declines in non-responding patients. The higher scores at baseline in the patients destined for response raises the intriguing possibility that QOL at AZA start may be independently predictive of response perhaps because of improved tolerability and ability to remain on drug for the requisite number of cycles to achieve response. Disclosures: Wells: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Buckstein:Celgene: Honoraria, Research Funding.

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Pomalidomide (POM) Plus Low-Dose Dexamethasone (LoDEX) Improves Health-Related Quality Of Life (HRQoL) Vs High-Dose Dexamethasone (HiDEX) In Relapsed Refractory Multiple Myeloma (RRMM) Patients Enrolled In MM-003 Phase 3 Randomized Trial

Blood ◽

10.1182/blood.v122.21.2939.2939 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2939-2939 ◽

Cited By ~ 2

Author(s):

Kevin W. Song ◽

Meletios A. Dimopoulos ◽

Katja Weisel ◽

Michel Delforge ◽

Lionel Karlin ◽

...

Keyword(s):

Health Status ◽

Global Health ◽

Board Of Directors ◽

Physical Functioning ◽

Research Funding ◽

Emotional Functioning ◽

Global Health Status ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership

Abstract Background Pronounced symptoms, poor prognosis, and therapy exhaustion each affect HRQoL in RRMM patients. The MM-003, randomized, multicenter, open-label phase 3 trial reported that POM + LoDEX significantly extended median progression-free and overall survival vs HiDEX in RRMM patients who exhausted bortezomib (BORT) and lenalidomide (LEN), and progressed on their last treatment (San Miguel, EHA, 2013). Improved survival outcomes, treatment-related toxicity, and aging populations have placed an emphasis on HRQoL in RRMM. MM-003 is the first study to investigate HRQoL in RRMM patients treated with POM + LoDEX. Methods Patients were randomized 2:1 to receive 28-day cycles (C) of POM 4 mg D1-21 + LoDEX 40 mg (20 mg for patients aged > 75 years) weekly or HiDEX 40 mg (20 mg for patients aged > 75 years) D1-4, 9-12, and 17-20 until disease progression or unacceptable toxicity. HiDEX was chosen as the comparator to isolate the effects of POM as at the time of trial design, it was the standard salvage therapy for heavily pretreated patients. Time to meaningful worsening in HRQoL was analyzed for 5 predefined EORTC QLQ-C30 domains (Global Health Status, Physical Functioning, Fatigue, Emotional Functioning, and Pain) using the Kaplan-Meier method. A meaningful worsening was defined as a reduction in HRQoL equal to or greater than the domain-specific minimally important difference, calculated using the standard error of measurement. HRQoL was also evaluated cross-sectionally and longitudinally through a mixed effect model. Data from the September 7, 2012 data cut are presented below. Results 455 patients were randomized to POM + LoDEX (n = 302) or HiDEX (n = 153). 448 patients completed at least 1 QLQ-C30 questionnaire and were included in the HRQoL analysis. The median number of prior treatments was 5 (range, 2-17), and 82% were refractory to LEN and BORT. Median follow-up was 4.2 months. Analyses on time to clinically meaningful worsening showed that POM + LoDEX extended median time to meaningful worsening vs HiDEX for all the preselected domains (Table): Global Health Status (114 vs 85 days, P = .06), Physical Functioning (174 vs 106 days; P = .09), Fatigue (113 vs 60 days; P = .04), Emotional Functioning (190 vs 124 days; P = .02), and Pain (147 vs 113 days; P = .2). In the cross-sectional analysis, HRQoL scores were relatively better for POM + LoDEX vs HiDEX for all domains at every cycle. Statistically or marginally significant (P < .10) treatment differences were observed for Global Health Status (C2 and 4), Physical Functioning (C2, 3, and 4), Emotional Functioning (C3), and Fatigue (C2) domains. No statistically significant deteriorations from baseline were observed in the mean scores for the POM + LoDEX arm for any of the 5 domains at any treatment cycle. Such deteriorations were observed with HiDEX. These results were supported by a mixed effect model analysis. Data from the March 1, 2013 data cut will be presented at the meeting. Conclusions In heavily pretreated patients who exhausted BORT and LEN, POM + LoDEX resulted in better clinical outcomes and favorable HRQoL vs patients treated with HiDEX. POM + LoDEX should become a standard of care in relapsing patients as it has been proven to prolong and enhance the lives of RRMM patients. Disclosures: Song: Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Off Label Use: POM is approved in the US but not in Europe. Dimopoulos:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Weisel:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria. Delforge:Celgene: Honoraria. Karlin:Celgene: Export board committee Other, Honoraria; Janssen: Honoraria. Goldschmidt:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Moreau:Celgene: Honoraria, Speakers Bureau. Oriol:Celgene: Consultancy. Spencer:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Knop:Celgene: Honoraria. Renner:Celgene: Consultancy, Honoraria, Travel support Other. Bahlis:Celgene: Consultancy, Honoraria, Research Funding. Amatya:Celgene: Consultancy. Yu:Celgene: Employment, Equity Ownership. Monzini:Celgene: Employment, Equity Ownership. Sternas:Celgene: Employment, Equity Ownership. Zaki:Celgene: Employment, Equity Ownership. Jacques:Celgene: Employment, Equity Ownership. San Miguel:Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.

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Patient-Reported Quality of Life In Elderly, Newly Diagnosed Multiple Myeloma Patients Treated with Bortezomib-Based Regimens: Results From the Phase 3b UPFRONT Study

Blood ◽

10.1182/blood.v116.21.3026.3026 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3026-3026 ◽

Cited By ~ 1

Author(s):

Ruben Niesvizky ◽

Ian W. Flinn ◽

Robert M. Rifkin ◽

Nashat Y Gabrail ◽

Veena Charu ◽

...

Keyword(s):

Health Status ◽

Global Health ◽

Treatment Period ◽

Research Funding ◽

Global Health Status ◽

Status Score ◽

Patient Reported ◽

Equity Ownership ◽

Eortc Qlq ◽

Health Status Score

Abstract Abstract 3026 Background: UPFRONT is an ongoing US community-based phase 3b study designed to compare the safety and efficacy of three bortezomib (Velcade®, Vc)-based regimens, Vc-dexamethasone (VcD), Vc-thalidomide-dexamethasone (VcTD), and Vc-melphalan-prednisone (VcMP), followed by Vc maintenance therapy, in previously untreated multiple myeloma (MM) patients who were ineligible for high-dose therapy and autologous stem cell transplantation (HDT-SCT). Efficacy data have been presented elsewhere; here we present patient-reported quality of life (QoL) data after 300 patients had the opportunity to undergo the entire 13-cycle treatment period (8 Vc-based induction cycles and 5 Vc maintenance cycles). Methods: Patients with symptomatic, measurable MM were randomized (1:1:1) to receive 49 weeks of therapy: 24 weeks (eight 21-day cycles) of induction with VcD, VcTD, or VcMP (VcD: Vc 1.3 mg/m2, days 1, 4, 8, 11; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [cycles 1–4]), days 1, 2, 4, 5 [cycles 5–8]); VcTD: Vc 1.3 mg/m2, days 1, 4, 8, 11; T 100 mg/d, d1–21; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [cycles 1–4]), days 1, 2, 4, 5 [cycles 5–8]); VcMP: Vc 1.3 mg/m2, days 1, 4, 8, 11; M 9 mg/m2, and P 60 mg/m2, day 1–4, every other cycle), followed by 25 weeks (five 35-day cycles) of maintenance with Vc alone (1.6 mg/m2, days 1, 8, 15, 22). Patient-reported QoL was recorded using the EORTC QLQ-C30 questionnaire, which assesses global health status, physical, role, cognitive, emotional, and social functions, fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Patients completed the questionnaire prior to dosing on cycle 1, day 1 (baseline), prior to dosing on day 1 of every odd cycle, at the end of treatment visit, and every 12 weeks thereafter. Here we present updated study results after 300 patients had the opportunity to undergo the entire 13-cycle treatment period, focusing on change in global health status score over time; no adjustment was made for missing cases or patient deaths. Results: Patient baseline characteristics were well balanced across the three treatment arms. Patients in the VcD, VcTD, and VcMP arms had median ages of 73.5, 73.0, and 72.0 years, respectively; 85%, 64%, and 74% had ISS stage II/III; 22%, 27%, and 28% were non-Caucasian; and 51%/25%/24%, 55%/30%/14%, and 62%/24%/15% had Charlson comorbidity index 0/1/≥2 in the VcD, VcTD, and VcMP arms, respectively. Patients received a median of 9 (VcD), 6 (VcTD), and 7 (VcMP) treatment cycles (induction + maintenance); 56%, 33%, and 43% of patients, respectively, received Vc maintenance. In the VcD, VcTD, and VcMP arms, Vc dose intensity (mean ratio of doses received/doses planned) was 76%, 63%, and 69% during induction, and 73%, 77%, and 85% during maintenance, respectively. After 13 treatment cycles, the rates of grade ≥3 adverse events (AEs) were 74%, 86%, and 80% in the VcD, VcTD, and VcMP arms. The incidence of serious AEs was highest in the VcTD arm (61%, vs 57% and 51% with VcD and VcMP), as was the rate of study drug discontinuation due to AEs (41%, vs 29% and 35% with VcD and VcMP). Global health status score by cycle is shown in the Figure, with number of patients with available QoL data in each arm indicated below. In all three arms, for those patients with available QoL data, global health status score at the end of cycle 12 was greater than at baseline and at the end of cycle 8 (end of Vc-based induction therapy). In the induction phase, global health status score remained stable in the VcD arm and transiently decreased in the VcMP arm at cycle 4, before increasing to above baseline levels. A similar trend was seen for the VcTD arm; global health status score started decreasing at cycle 2 but took slightly longer to increase, possibly due to the increased incidence of AEs in the VcTD arm. Similar trends were seen for other EORTC QLQ-C30 function and symptom scores. Conclusions: Although there was some variability during the study, by the end of the treatment period patients who received one of the three Vc-based regimens reported improvements in QoL compared with baseline values. The study is ongoing and patients continue to be followed for assessment of patient-reported QoL and long-term outcomes. Updated QoL data, including the correlation between change in QoL and best response achieved, will be presented. Disclosures: Niesvizky: Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Consultancy, Research Funding; Onyx: Consultancy, Research Funding. Off Label Use: Discussion of Velcade in a novel combination in frontline myeloma is included. Flinn:Millennium Pharmaceuticals, Inc.: Research Funding. Rifkin:Millennium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Speakers Bureau; Cephalon: Speakers Bureau; Dendreon: Speakers Bureau. Gabrail:Millennium Pharmaceuticals, Inc.: Research Funding. Charu:Amgen: Equity Ownership, Research Funding; Pfizer: Equity Ownership; GSK: Equity Ownership, Research Funding; Lilly: Equity Ownership, Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Roche: Research Funding; Bristol-Myers Squibb: Equity Ownership. Neuwirth:Millennium Pharmaceuticals, Inc.: Employment. Corzo:Millennium Pharmaceuticals, Inc.: Employment. Reeves:Celgene: Equity Ownership.

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Association of Changes in Transfusion Status with Changes in Health-Related Quality of Life of Real-World Patients with MDS Across Six Months of Treatment with Azacitidine

Blood ◽

10.1182/blood.v118.21.2796.2796 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2796-2796

Author(s):

Chris L. Pashos ◽

David L. Grinblatt ◽

Mikkael A. Sekeres ◽

Rami S. Komrokji ◽

Mohit Narang ◽

...

Keyword(s):

Health Status ◽

Global Health ◽

Board Of Directors ◽

Global Health Status ◽

Employment Equity ◽

Advisory Committees ◽

Transfusion Independence ◽

Related Quality ◽

Equity Ownership ◽

Rbc Transfusion

Abstract Abstract 2796 Introduction: The health-related quality of life (HRQOL) of patients with myelodysplastic syndromes (MDS) is worse if they are red blood cell transfusion dependent (RBC TD) than if they are RBC transfusion independent (TI). Little is known whether a change in status from RBC TD to RBC TI is associated with improved HRQOL. This analysis characterized the HRQOL of real-world patients with MDS across 6 months of treatment with Azacitidine (AZA) by their RBC TD/TI status. Methods: Data were collected from AVIDA®, a prospective, US, community-based registry of patients treated with AZA. Patients with MDS who were originally RBC TD at baseline, and who received 56 days or more of AZA were analyzed. RBC TD, defined as having received > 1 RBC transfusion within 56 consecutive days, was determined and verified centrally. Clinicians provided data on patient demographics and clinical characteristics, including RBC transfusions. Patients reported HRQOL by completing the EORTC-QLQ-C30 instrument at baseline and quarterly thereafter. Summary statistics (e.g., mean scores and changes in scores) on global health status, five functional scales, and nine symptom/other scales were analyzed. Statistical significance was ascertained by ANOVA using SAS 9.1. Results: In the full AVIDA cohort, 328 MDS patients received at least 56 days of treatment with AZA, of whom 153 reported HRQOL data at baseline and at six months. At baseline, 85 of the 153 were RBC TD, while the rest were RBC TI. At six months, 41 of the 85 had become RBC TI, while 44 remained RBC TD. Global health status improved among those who became RBC TI, but declined among those who stayed RBC TD. Statistically significant and clinically meaningful (i.e., greater than 7 points) differences in change between baseline and 6 months also were seen in physical and role function, but not in emotional, cognitive or social function. Fatigue was the only symptom score in which changes were statistically significantly different between groups, with RBC TI patients reporting less fatigue, and RBC TD patients reporting more. Conclusions: Findings from AVIDA® indicate that HRQOL among RBC TD MDS patients treated with AZA improves significantly overall and on certain domains if they achieve RBC transfusion independence. The improved global health status; better physical and role functioning; and less fatigue associated with RBC TD patients achieving RBC transfusion independence should be recognized by US clinicians as they manage patients with MDS. Disclosures: Pashos: 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. Sekeres:Celgene: Consultancy, Honoraria, Speakers Bureau. Komrokji:Celgene: Honoraria, Research Funding, Speakers Bureau. Narang:Celgene: Membership on an entity's Board of Directors or advisory committees. Swern:Celgene Corporation: Employment, Equity Ownership. Street:Celgene: Employment, Equity Ownership. Sullivan:Celgene: Employment, Equity Ownership. Khan:Celgene: Employment, Equity Ownership.

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

Blood ◽

10.1182/blood.v124.21.709.709 ◽

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.

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Patient-Reported Health-Related Quality of Life Improves over Time in Patients with Chronic Immune Thrombocytopenia Receiving Long-Term Treatment with Eltrombopag

Blood ◽

10.1182/blood.v128.22.3750.3750 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3750-3750 ◽

Cited By ~ 2

Author(s):

Abderrahim Khelif ◽

Mansoor N. Saleh ◽

Abdulgabar Salama ◽

Paul Burgess ◽

Maria do Socorro O Portella ◽

...

Keyword(s):

Health Status ◽

Board Of Directors ◽

Research Funding ◽

Term Treatment ◽

Physical And Mental Health ◽

Advisory Committees ◽

Long Term Treatment ◽

Patient Reported ◽

Related Quality ◽

Over Time

Abstract Background: EXTEND (June 2006 to July 2015) was an open-label, dose-adjustment extension study to evaluate the safety and efficacy of eltrombopag for the treatment of patients with chronic immune thrombocytopenia (cITP) who had previously been enrolled in an eltrombopag trial. CITP may lead to fatigue and interference with daily activities, and ultimately affect health-related quality of life (HRQoL). Objective: To assess patient-reported HRQoL changes over time during long-term treatment with eltrombopag in patients with cITP using the final EXTEND data. Methods: Four standard validated HRQoL instruments for chronic disease were used in this study: SF-36v2 including the Physical Component Summary (PCS) and Mental Component Summary (MCS) to measure general physical and mental health status; Motivation and Energy Inventory Short Form (MEI-SF) to measure motivation and energy; Fatigue Subscale of FACIT (FACIT-F) to measure symptoms of fatigue; and FACT-Thrombocytopenia Subscale Six-Item Extract (FACT-Th6) to measure concerns related to bleeding and bruising and their impact on usual activities. The instruments were used at baseline (BL) and at a frequency of every 3 months until last on-treatment assessment. Patients were blinded to their current platelet count results before completing the questionnaires. Generalized estimating equations were used to estimate mean changes in HRQoL from BL to different time periods for each instrument, accounting for within-patient correlation. The models adjusted for time period from BL, demographic characteristics, BL clinical characteristics (BMI, BL use of cITP medication, prior splenectomy, prior eltrombopag use, and BL platelet count), and time-varying covariates for rescue therapy use (defined as the composite of new cITP medication, increased dose of cITP medication from BL, platelet transfusion, and splenectomy). Adjusted mean best changes in HRQoL from BL were also estimated using a similar method. Proportions of responders based on minimally important difference (MID) from BL were identified for each of the instruments. Response was defined as a change from BL score of at least one-half the standard deviation (SD) of the normalized scores (5 points) for SF-36v2 PCS and SF-36v2 MCS, at least one-half the SD of BL scores observed across all patients for MEI-SF and FACT-Th6, and at least 3 or 5 points for FACIT-F. Proportions of patients achieving any improvement and time to best improvement from BL were also reported. Results: 302 patients were enrolled in EXTEND. By instrument, 289 to 293 patients had a BL and at least one on-treatment HRQoL assessment for analysis. Median treatment duration was 2.4 years. All HRQoL instruments had positive mean changes from BL over time; noticeably improvements from BL persisted through 5 years of treatment for FACIT-F and FACT-Th6 (nearly all p<0.05) (Table 1) and through the median duration of eltrombopag treatment for SF-36v2 PCS. All HRQoL instruments had a statistically positive and clinically meaningful (greater than MID threshold) mean best change from BL (p<0.01) (Table 2). About half of patients had a response at least once during treatment based on MIDs in changes from BL: 45.4% (SF-36v2 PCS); 44.7% (SF-36v2 MCS); 42.3% (MEI-SF); 57.5% (3 points) and 47.3% (5 points) for FACIT-F; and 49.5% (FACT-Th6). Most patients experienced an improvement from BL (a higher post-baseline score at least once): 84.9% (SF-36v2 PCS); 82.8% (SF-36v2 MCS); 79.9% (MEI-SF); 77.1% (FACIT-F); and 80.6% (FACT-Th6). Best improvement occurred at a median of 6-10 months post BL. Conclusion: About 80% of patients with cITP treated with eltrombopag experienced an improvement from BL in HRQoL, often within a year of BL. About half of patients achieved a clinically meaningful response from BL. This study found positive and meaningful mean best changes from BL in all HRQoL scores, including those measurements more closely related to clinical outcomes such as fatigue, bleeding, and bruising as well as more general measures such as motivation, energy, physical and mental health status. Improvements from BL persisted over time in particular for fatigue, bleeding, bruising, and physical health status. Disclosures Saleh: GSK: Consultancy, Research Funding, Speakers Bureau. Burgess:Novartis: Employment. Portella:Novartis: Employment. Roy:Novartis: Employment. Barghout:Novartis: Consultancy. Ivanova:Novartis: Research Funding; GSK: Research Funding; Teva: Research Funding; Lilly: Research Funding. Bussel:GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Rigel Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; UpToDate: Patents & Royalties; Boehringer Ingelheim: Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees; Genzyme: Research Funding; Protalex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prophylix Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sysmex: Research Funding; BiologicTx: Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Physicians Education Resource: Speakers Bureau; Momenta Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Symphogen: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Rationale and Design of a Phase 3 Study to Evaluate the Efficacy and Safety of ION-682884 in Patients with Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)

Blood ◽

10.1182/blood-2019-129269 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5764-5764 ◽

Cited By ~ 1

Author(s):

Rodney H Falk ◽

Morie A Gertz ◽

Merrill D Benson ◽

Gustavo Buchele ◽

Michela Brambatti ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Parent Compound ◽

Controlled Study ◽

Efficacy And Safety ◽

Phase 3 ◽

Advisory Committees ◽

Study Visit ◽

Clinical Events ◽

Patient Reported

Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a life-threatening, irreversible condition, which can lead to heart failure (HF) and, ultimately, heart transplant or death. Despite the recent approval in United States of a TTR stabilizer (VYNDAQEL®-tafamidis meglumine;VYNDAMAX™-tafamidis) for the treatment of ATTR-CM, disease progression still occurs. This study aims to determine if treatment with AKCEA-TTR-LRx (ION-682884), an antisense oligonucleotide (ASO), is safe and superior to placebo in reducing the risk of cardiovascular (CV) death or CV clinical events in patients with hereditary (hATTR-CM) or wild-type ATTR-CM (wtATTR-CM). Study Design and Methods: AKCEA-TTR-LRx (ION-682884) is a follow-on compound that incorporates the Ligand-Conjugated Antisense (LICA) technology; in this case, a triantennary N-acetyl galactosamine (GalNAc) moiety which targets the asialoglycoprotein receptors (ASGPR) expressed abundantly on the hepatocyte cell surface. In comparison to inotersen, its parent compound, ION-682884 requires a lower dose and frequency of administration (27-fold smaller; 45mg SC Q4W) to achieve a similar reduction in ATTR, providing greater patient convenience. ION-682884-CS2 (EudraCT No: 2019-002835-27) is a Phase 3 global, double-blind, randomized, placebo-controlled study assessing the efficacy and safety of AKCEA-TTR-LRx (ION-682884) in hATTR-CM or wtATTR-CM patients receiving available background standard of care (SoC) therapy. Approximately 750 patients with a history of HF due to ATTR-CM will be randomized 1:1 to receive AKCEA-TTR-LRx (ION-682884) or placebo administered by subcutaneous injection once every 4 weeks. The main inclusion criteria include confirmed diagnosis of ATTR-CM by tissue biopsy or positive PYP/DPD scan, end-diastolic interventricular septum thickness of >12mm, NT-proBNP >600 pg/mL, NYHA class I-III and 6-minute walk distance (6MWD) >150 m. The main exclusion criteria include estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2, platelet count below the low limit of normality and urine protein/creatinine ratio (UPCR) ≥ 1000 mg/g. Patients are allowed to concomitantly receive tafamidis/tafamidis meglumine as SoC for ATTR-CM, if locally approved and available, per physician's discretion. The study consists of a 120-week Treatment Period and a 20-week Post-Treatment Evaluation Period. During each study visit, subjects will undergo laboratory tests, cardiac assessments (echocardiography), and functional evaluations. Patient-reported outcomes (PRO) will also be collected. Primary efficacy endpoint is the composite of CV mortality and frequency of CV clinical events (HF-related urgent visits requiring administration of IV diuretics and/or CV-related hospitalizations) at Week 120 study visit, analyzed by the Finkelstein-Shoenfeld method. This test is based on the principle of each patient in the study being compared with every other patient in a pairwise manner in hierarchical fashion. Secondary endpoints include the change from baseline in the 6MWD, Kansas City Cardiomyopathy Questionnaire score, rate of CV mortality, CV clinical events, and all-cause of mortality at Week 120. Additional exploratory endpoints include a change from baseline in cardiac imaging parameters, renal function, biomarkers, and PROs questionnaires and disease scores. An interim analysis on change from baseline in 6MWD is also planned at Week 60. All deaths and CV clinical events will be adjudicated by an independent, blinded Clinical Adjudication Committee, using predefined endpoint criteria. Conclusions: Despite recent advances, there is still a need for more efficacious, safe and convenient treatment options for ATTR-CM. The ION-682884-CS2 is a large Phase 3 trial designed to evaluate the clinical efficacy and safety of AKCEA-TTR-LRx (ION-682884) compared to placebo for the treatment of ATTR-CM. Figure Disclosures Falk: Ionis Pharmaceuticals: Consultancy. Gertz:Ionis/Akcea: Consultancy; Alnylam: Consultancy; Proclara: Membership on an entity's Board of Directors or advisory committees; Prothena Biosciences Inc: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; Appellis: Consultancy; Amgen: Consultancy; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Research to Practice: Consultancy; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; i3Health: Other: Development of educational programs and materials; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding. Benson:Ionis Pharmaceuticals: Research Funding. Buchele:Ionis Pharmaceuticals: Employment. Brambatti:Ionis Pharmaceuticals: Employment. Tsimikas:Ionis Pharmaceuticals: Employment. Viney:Ionis Pharmaceuticals: Employment. Tai:Ionis Pharmaceuticals: Employment. Monteiro:Ionis Pharmaceuticals: Employment. Yang:Ionis Pharmaceuticals: Employment. O'Dea:Akcea Therapeutics: Employment. Karwatowska-Prokopczuk:Akcea Therapeutics: Employment. Schneider:Ionis Pharmaceuticals: Employment. Geary:Ionis Pharmaceuticals: Employment. Monia:Ionis Pharmaceuticals: Employment.

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Elipsis: A Longitudinal Study of Electronic Patient-Reported Outcomes, Actigraphy and Biomarkers to Identify and Assess at-Home Vaso-Occlusive Crises in Adults and Adolescents with Sickle Cell Disease

Blood ◽

10.1182/blood.v130.suppl_1.973.973 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 973-973

Author(s):

Michael U. Callaghan ◽

Patrick C. Hines ◽

Debra D Pittman ◽

David Beidler ◽

Denis Rybin ◽

...

Keyword(s):

Clinical Trials ◽

Board Of Directors ◽

Research Funding ◽

Patient Reported Outcomes ◽

Clinical Laboratory ◽

Advisory Committees ◽

Pain Scores ◽

Patient Reported ◽

Platelet Aggregates ◽

At Home

Abstract Clinical trials in sickle cell disease (SCD) continue to have challenges achieving clinical endpoints. Most SCD clinical trials have focused on painful vaso-occlusive crisis (VOC) episodes because they are prevalent, debilitating and often lead to medical contact. However with VOC as a clinical endpoint: there are no objective, quantifiable biomarkers of pain; pain may not be specific to VOC; the threshold for medical contact varies between patients; VOCs occurring at home without medical contact are not captured; other components of VOC (e.g., fatigue, functioning) are poorly assessed. We therefore undertook the present non-interventional, longitudinal study to test novel tools for the identification of VOCs occurring in SCD patients with varying degrees of medical contact. During 6 months of evaluation, longitudinal measures of pain, fatigue, function, activity (by actigraphy), clinical laboratory and biomarker samples from SCD patients (+/- hydroxyurea therapy) in steady state to VOC were studied. A novel electronic patient-reported outcome tool (ePRO) enabled patients to self-report daily pain, fatigue, function, and medication use. It was also used to report VOC in real time, triggering an alert to a mobile phlebotomy team. Blood collections were taken within 24 and 48 hours of self-reported VOC onset (either at home, emergency department [ED], or hospital). Follow-up blood samples were collected 2 days after resolution of the VOC. Baseline blood samples were drawn at home every 3 weeks during stable, non-VOC periods. Biomarker assays included leukocyte-platelet aggregates and circulating microparticles measured by flow cytometry, cell adhesion in microfluidic flow-based assays to immobilized vascular cell adhesion molecule or P-selectin, and a panel of soluble adhesion molecules, cytokines, inflammatory mediators and coagulation factors. Patients wore a Phillips Actiwatch Spectrum™ actigraphy device to track sleep and activity. Patient-reported outcomes, activity, and biomarkers on non-VOC days were compared to those on VOC days using a mixed model approach and results are reported as means with 95% confidence intervals (95%CI). In this study 27 of 35 patients experienced a total of 286 days with VOC >4 hr (VOC days), of which only 58 days (20%) resulted in healthcare utilization such as contacting provider, visiting ED and/or hospitalization. VOC days had significantly higher pain scores (scale: 0-10) with worst pain score increased by 4.5 (95% CI 4.3-4.7) compared to non-VOC days. VOCs requiring medical contact had significantly higher worst pain scores compared to at-home VOCs. Similar changes observed with reported least, average and pain right now. VOC days had significantly higher fatigue scores by 2.3 (95% CI 2.1-2.5) points (scale: 0-10). However, fatigue scores during at-home VOCs were not different from VOCs requiring medical contact. VOC days were associated with significantly decreased functional scores (physical, social, self-care and role activity), with significantly greater decreases during VOCs requiring medical contact compared to at-home VOCs. Different activity profiles were identified for non-VOC, at-home VOC and medical contact VOC days by actigraphy monitoring. At-home VOC days exhibited increased (34%, 95% CI 9%-64%) daytime resting compared to non-VOC days. Medical contact VOCs had decreased average and peak activity, and increased daytime resting compared to non-VOC days. A sleep fragmentation index trended up for both at-home (16%) and medical contact VOC days (18%). Significant changes during VOC days were observed in a subset of clinical laboratory and biomarker measures. Examples include: C-reactive protein (54% increase) and nucleated RBC (34% increase) in the clinical laboratory panel; monocyte-platelet aggregates (25% increase) and neutrophil-platelet aggregates (35% increase) in the biomarker panel. This innovative at-home study design demonstrates the feasibility of monitoring out of hospital pain and use of patient-reported VOC day as a potential endpoint for clinical trials. Electronic patient-reported outcomes, actigraphy and clinical laboratory and biomarkers may enable improved identification and assessment of at-home VOCs for further clinical studies. Disclosures Callaghan: CSL Behring: Membership on an entity's Board of Directors or advisory committees; Grifols: Membership on an entity's Board of Directors or advisory committees; Biogen: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Other: Site PI; Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Site PI, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees; Alnylam Pharmaceuticals, Inc: Other: Owns stock, stock options, or bonds ; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer HealthCare; Pfizer Inc.; Roche; Shire: Consultancy; Sancillio: Other: Site PI; Bayer: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc.: Membership on an entity's Board of Directors or advisory committees, Other: Site PI, Research Funding; Roche; Shire: Speakers Bureau; Novo Nordisk: Speakers Bureau. Pittman: Pfizer: Employment. Beidler: Pfizer: Employment. Rybin: Pfizer: Employment. Liu: Functional Fluidics: Employment. Pleil: Pfizer: Employment. Barsdorf: Pfizer: Employment. David: Pfizer: Employment. Simmons: Pfizer: Employment. Frelinger: Baxalta: Research Funding; Ionis: Research Funding; Sysmex: Research Funding; Pfizer: Research Funding; Ironwood: Research Funding; GLSynthesis: Research Funding. Michelson: Eisai: Research Funding; Ionis: Research Funding; Ironwood: Research Funding; Pfizer: Research Funding; Sysmex: Research Funding; GLSynthesis: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Instrumentation Laboratory: Consultancy; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Elsevier: Patents & Royalties; Baxalta: Research Funding. Clarke: Pfizer: Employment. Charnigo: Pfizer: Employment.

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177Lu-PSMA-617 (LuPSMA) versus cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel: Updated results including progression-free survival (PFS) and patient-reported outcomes (PROs) (TheraP ANZUP 1603).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.6 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 6-6

Author(s):

Michael S Hofman ◽

Louise Emmett ◽

Shahneen Kaur Sandhu ◽

Amir Iravani ◽

Anthony M. Joshua ◽

...

Keyword(s):

Health Status ◽

Global Health ◽

Objective Response ◽

Progression Free Survival ◽

Global Health Status ◽

Castration Resistant Prostate Cancer ◽

Promising Alternative ◽

Clinical Endpoints ◽

Point Reduction ◽

Patient Reported

6 Background: TheraP is a randomized phase 2 trial that showed LuPSMA significantly improved the primary endpoint of PSA≥50% reduction (66% vs. 37%) compared to cabazitaxel in men with docetaxel-treated mCRPC. We now report results on other clinical endpoints and PROs reached the pre-specified target of 170 PFS events. Methods: 200 men with mCRPC (median age 72 y, prior enza/abi 91%) and high PSMA-expression by 68Ga-PSMA-11 and no sites of FDG-positive/PSMA-negative disease, were randomly assigned (1:1) to LuPSMA (6-8.5GBq q6wk up to 6 cycles; N = 99) or cabazitaxel (20mg/m2 q3wk up to 10 cycles; N = 101). Secondary endpoints include PSA/radiologic PFS (PCWG3), pain response (≥2 point reduction on McGill-Melzack Present Pain Intensity scale, objective response rate (ORR) (RECIST 1.1), adverse events (CTCAE), PROs (EORTC QLQ-C30) and overall survival (OS). Cut-off date for analysis of 20JUL20. Results: At a median follow-up of 18.4 months, PFS was significantly longer in those assigned Lu-PSMA rather than cabazitaxel (rates at 1y 19% [95%CI 12-27%] vs 3% [1-9%], hazard ratio (HR) 0.63, 95%CI 0.46-0.86; p = 0.003; 173 events). Similar benefit was seen for rPFS (HR 0.64, 95%CI 0.46-0.88; p = 0.007; 160 events) and PSA-PFS (HR 0.60 95%CI 0.44-0.83; p = 0.002; 172 events). ORR in 78 men with measurable disease was significantly greater in the LuPSMA arm (49% vs 24%, RR 2.1, 95%CI 1.1-4.1; p = 0.019). In 90 men with pain at baseline, pain responses occurred in 60% in the Lu-PSMA arm vs 43% for cabazitaxel (RR 1.42, 95%CI 0.84-4.48; p = 0.10). Patient-reported global health status was similar (LuPSMA 64 [95%CI 61-67] vs cabazitaxel 60 [57-64]) with significantly better outcomes reported for fatigue (34 [95%CI 31-37] vs 40 [36-43]), social functioning (79 [76-82] vs 73 [69-77]), insomnia (24 [20-27] vs 29 [25-33]) and diarrhoea (8.3 [5.6-11.0] vs 15.6 [12.6-18.6]) domains. No PRO domains were superior for cabazitaxel. G3-4 AEs were similar to previously reported (33% vs 53%). OS data remains immature (90 deaths). Conclusions: In men with docetaxel-treated mCRPC, LuPSMA is a promising alternative to cabazitaxel with significantly higher activity (PSA≥50%, PFS, ORR), fewer G3-4 AEs, similar effects on global health status, and improvements in some PRO domains. Clinical trial information: NCT03392428.

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Health-Related Quality of Life Impairment in Patients with Chronic Myeloid Leukemia: Results of a German Cross-Sectional Study of Patients Registered in Prospective, Controlled Clinical Trials

Blood ◽

10.1182/blood.v126.23.2773.2773 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2773-2773 ◽

Cited By ~ 1

Author(s):

Susanne Saussele ◽

Mareike Stein ◽

Arthur Gil ◽

Ute Kossak-Roth ◽

Michael Lauseker ◽

...

Keyword(s):

Health Status ◽

Global Health ◽

Cognitive Functioning ◽

Research Funding ◽

Cross Sectional Study ◽

Global Health Status ◽

German Population ◽

Cross Sectional ◽

Travel Grant ◽

Advisory Role

Abstract Introduction: With many treatment options for chronic myeloid leukemia (CML), endpoints like health-related quality of life (HRQoL) move into focus and might be essential for deciding on treatment strategies. We sought to evaluate HRQoL in CML patients who had been registered in four consecutive studies of the German CML study group. Methods: The EORTC QLQ-C30 questionnaire was used to assess HRQoL of CML patients. Functional scales and global health status were calculated in accordance with Aaronson (1993) and Fayers (2001). With scales ranging from 0 to 100, 8 points are regarded as a minimally important difference (Efficace et al., 2013). Baseline data of responders (R) and non-responders (NR) were compared. Associations between two variables were assessed by the Fisher or Mann-Whitney tests, as appropriate. The global health status and the functioning scores were compared between groups with the van Elteren test, if the groups were stratified for another variable. Furthermore, results of the global health status and the functioning scores in our sample were standardized in accordance with the age (18-29, 30-39, 40-49, 50-59, 60-69, ≥70 years) and sex distribution of the 2448 participants of the German HRQoL outcome study reported by Hinz et al. 2014. The outcome of our sample was then compared with the outcome of these 2448 patients representing QoL of the German population in general. Comparison was performed using a t test. Results: A questionnaire was sent to 1634 patients. During January to April 2011, 858 questionnaires (53%) were sent back. Compared to NR, R were older (median age: 55 vs. 58, p=0.0426); years since diagnosis (median 6.5 vs. 7.4) and the percentage that had been transplanted were lower (24%vs.18%). No differences were observed regarding sex, Euro score, or time after allogeneic hematopoietic stem cell transplantation (HSCT). When answering the questionnaire, 517 (60%) patients received imatinib 400mg (IM400) and 102 (12%) were off therapy after HSCT. Less than 10% of patients received imatinib 800mg, imatinib+AraC or interferon alpha, nilotinib, or dasatinib. Time since diagnosis was ≤3 years in 156 (18%), >3 and ≤7 years in 309 (36%), and >7 years in 393 (46%) of the patients. Women (352, 41%) perceived a significant reduction in global health status (mean: 62.7, p<0.001), role (65.4, p=0.0016), emotional (60.3, p=0.0002), and physical functioning (74.9, p<0.0001) when compared to males (68.9, 71.5, 67.6, and 82.7, respectively). In the latter two cases, this perception met the definition of a clinical relevance. Results on significance did not change with adjustment for age. Compared to the German population, the 858 CML patients had significantly lower scores for global health status (mean: 67.9, p<0.0001), role (70.8, p<0.0001), social (69.2, p<0.0001), emotional (64.6, p<0.0001), physical (81.0, p<0.0001) and cognitive functioning (77.3, p<0.0001). Only for global health status, the difference was below 8. To evaluate HRQoL in patients with long standing disease, 100 patients with diagnosis >7 years off therapy after HSCT and 203 patients receiving IM400 were analyzed. Adjusted for age group and sex, CML patients receiving IM400 for more than 7 years had lower scores for global health status (mean: 63.8, p<0.0001 ), role (66.7, p<0.0001), social (68.8, p<0.0001), emotional (64.0, p<0.0001), physical (75.2, p<0.0001) and cognitive functioning (68.0, p<0.0001) than the German control population. With respect to all six HRQoL scores, significantly lower scores than from the German population were also observed for the CML patients being seven years without treatment after HSCT: global health status (mean: 69.2, p<0.0001 ), role (68.6, p<0.0001), social (67.5, p<0.0001), emotional (68.1, p<0.0001), physical (83.1, p<0.0001) and cognitive functioning (71.2, p=0.0053). Conclusions: In this cross-sectional study, women showed an impaired global health status, role, emotional, and physical functioning compared to males. Considering all 858 CML patients, the HRQoL was significantly impaired in all scales when compared to the German population. The same results were observed for the subgroups of patients either receiving IM400 for at least 7 years or being off therapy 7 years after HSCT. Reduced HRQoL remains an issue for all patients after long-term TKI treatment or after HSCT. These data may serve as a basis to evaluate HRQoL in stopping studies in CML. Disclosures Saussele: BMS: Honoraria, Other: Travel grant, Research Funding; Novartis Pharma: Honoraria, Other: Travel grant, Research Funding; ARIAD: Honoraria; Pfizer: Honoraria, Other: Travel grant. Kremers:Novartis: Honoraria; Bristol Myers Squibb: Other: Travel costs, supporting educational meeting; Novartis: Other: supporting educational meeting. Hochhaus:Bristol-Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding. Müller:BMS: Honoraria, Other: Consulting or Advisory Role, Research Funding; Novartis: Honoraria, Other: CONSULTING OR ADVISORY ROLE, Research Funding; ARIAD Pharmaceuticals Inc.: Honoraria, Other: Consulting & Advisory Role, Research Funding. Hehlmann:Novartis Pharma: Research Funding; BMS: Consultancy. Pfirrmann:BMS: Consultancy, Honoraria; Novartis Pharma: Consultancy, Honoraria.

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