Categorized Hematologic Response to Pegcetacoplan and Correlations with Quality of Life in Patients with Paroxysmal Nocturnal Hemoglobinuria: Post Hoc Analysis of Data from Phase 1b, Phase 2a, and Phase 3 Trials

Abstract Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a complement-mediated, hematologic disease characterized by hemolysis, anemia, and fatigue that impairs quality of life. Pegcetacoplan (PEG), a C3-inhibitor recently approved by the Food and Drug Administration for treatment of PNH, controls intravascular hemolysis (IVH) and prevents extravascular hemolysis (EVH). The PADDOCK and PALOMINO trials demonstrated PEG's improvement of key hematologic and clinical parameters, including hemoglobin (Hb) level and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score. The PEGASUS trial demonstrated that PEG was more effective than eculizumab (ECU) in improving these parameters in PNH patients with suboptimal response to prior ECU treatment. Aims: This post hoc analysis categorized hematologic response to PEG in 3 trials: PADDOCK (phase 1b, open-label, two-cohort [NCT02588833]), PALOMINO (phase 2a, open-label, single-cohort [NCT03593200]), and PEGASUS (phase 3, randomized, open-label, active-comparator controlled [NCT03500549]). Methods: PADDOCK and PALOMINO included adult complement inhibitor-naïve patients, while PEGASUS included adult patients with Hb <10.5 g/dL despite ≥3 months of ECU treatment. PADDOCK was a multiple ascending dose pilot study of 2 cohorts: cohort 1 received a suboptimal PEG dose (180 mg/day subcutaneously [SQ]) for 28 days; cohort 2 received a PEG dose of 270-360 mg/day SQ for up to one year. Patients could be enrolled in both cohorts. PALOMINO patients received a PEG dose of 270-360 mg/day SQ for up to one year. PEGASUS comprised a 4-week run-in period where patients received both ECU (continued dosing regimen) and PEG (1080 mg SQ twice-weekly), 16-week randomized controlled period (PEG or ECU monotherapy), and 32-week open-label period (PEG monotherapy) including a 4-week run-in period for the ECU-to-PEG group. Hematologic response category was assessed at Days 113/337 for patients in the combined PADDOCK/PALOMINO trials (N=24) via manual categorization by two independent, blinded observers. Categorization was assessed at Weeks 16/48 for PEGASUS patients (N=80) using SAS 9.4M5. Statistical significance for hematologic response categories within arms at Week 16 vs. 48, and between arms at Week 48, was evaluated using Wilcoxon-Mann-Whitney and Chi-square testing. FACIT-Fatigue scores for PEGASUS patients, summarized using descriptive statistics, were also correlated to hematologic response category. Response categories were defined per the following criteria (Risitano A, et al., Front Immunol, 2019;10:1157): complete- no transfusions required, stable Hb (normal range), no evidence of hemolysis (lactate dehydrogenase [LDH]≤1.5×upper limit of normal [ULN] U/L, absolute reticulocyte count [ARC]≤150,000/µL); major- no transfusion, normal Hb, but with evidence of hemolysis (LDH>1.5×ULN U/L and/or ARC>150,000/µL); good- no transfusions, but with chronic mild anemia or evidence of hemolysis; partial- chronic moderate anemia and/or occasional transfusions (<3 units/6 months); minor- regular transfusions required (3-6 units/6 months); no response- regular and frequent transfusions required (>6 units/6 months). PADDOCK/PALOMINO patients missing data at an assessment timepoint, or PEGASUS patients missing data within 6 weeks prior to an assessment timepoint, were not evaluated. Results: Most PADDOCK/PALOMINO patients achieved at least a good hematologic response at Days 113 and 337 (Table 1). At Week 48, most patients in both PEGASUS arms achieved a good/major/complete hematologic response (inter-arm p=0.4390), with a significant increase in the percent of ECU-to-PEG patients achieving at least a good response after switching to PEG at Week 16 (Week 16 vs. 48: intra-arm p<0.0001; Table 1). In PEGASUS, patients with better response categories had higher FACIT-Fatigue scores when compared to the rest of the cohort (Week 16: p<0.001, Week 48: p=0.028; Table 2). Conclusions: In post hoc analyses of PADDOCK, PALOMINO, and PEGASUS trial data, a substantial proportion of patients achieved and maintained good, major, or complete hematologic responses to PEG, suggesting that PEG can lead to sustained improvements in hematologic parameters. PEGASUS data also demonstrated correlation of improved hematologic response category with clinically meaningful improvements in quality of life, as measured by FACIT-Fatigue. Figure 1 Figure 1. Disclosures Risitano: Jazz: Other: Lecture fees, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees; Biocryst: Membership on an entity's Board of Directors or advisory committees; RA Pharma: Research Funding; Amyndas: Consultancy; Samsung: Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Research Funding, Speakers Bureau; Alnylam: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Research Funding, Speakers Bureau; F. Hoffmann-La Roche Ltd.: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Lecture fees, Speakers Bureau; Apellis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Speakers Bureau. Wong: Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Apellis Pharmaceuticals: Research Funding, Speakers Bureau; Alexion: Consultancy, Honoraria, Research Funding, Speakers Bureau. Al-Adhami: Apellis Pharmaceuticals: Current Employment. Chen: Apellis Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Peffault De Latour: Swedish Orphan Biovitrum AB: Consultancy, Honoraria; Apellis Pharmaceuticals: Consultancy, Honoraria; Alexion Pharmaceuticals: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.

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Evaluation of Health Related Questionnaire Among Mycosis Fungoides and Lymphomatoid Papulosis

Blood ◽

10.1182/blood.v126.23.5603.5603 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5603-5603 ◽

Cited By ~ 1

Author(s):

Rakhshandra Talpur ◽

Iris Wieser ◽

Casey Wang ◽

Lyons Genevieve ◽

Madeleine Duvic

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Mycosis Fungoides ◽

Research Funding ◽

Brentuximab Vedotin ◽

Function Score ◽

Advisory Committees ◽

Significant Difference ◽

And Function

Abstract INTRODUCTION AND OBJECTIVES: Mycosis Fungoides (MF) andlymphomatoid papulosis (LyP) are relatively rare and itchy skin disorders. The cosmetic disfigurement and severe pruritus dramatically affects the patient's quality of life. The focus is to examine the validity and reliability of the skindex-29, M.D. Anderson symptom inventory (MDASI) and itch-related quality of life (IQOL) questionnaire in 62 patients in a phase II trial of Brentuximab Vedotin. MATERIALS AND METHODS: Patients completed survey questionnaires related to symptoms and quality-of-life several times over the course of Brentuximab Vedotin. We compared patients' baseline scores to their end-of-study (EOS) scores. Patients were grouped by diagnosis into Mycosis Fungoides and Lymphomatoid papulosis group. Questionnaires included skindex-29, focusing on the skin conditions the patient was bothered the most. (MDASI) for patients with cancer and following the symptoms of cancer and the itchy quality of life (I-QoL) questionnaire was developed to measure the symptoms associated with cancer therapeutic agents and their effect on daily activities. Scoring for the Skindex-29, M. D. Anderson Symptom Inventory (MDASI) and the Quality of Life (QOL) survey were done according to the questionnaire specific scoring guide. Responses were compared between 2 groups using the Wilcoxon rank-sum test. RESULTS Questionnaires from 62 patients (23 LyP and 39 MF) were studied at baseline and end of study. Patients were 33 males and 29 females with median age of 60 years (range: 27-86 years). The median overall survival (OS) was significant P = 0.041, when comparing patients with MF to LyP. The median survival time for patients from time of diagnosis with MF was 14.66 years and LyP was not reached. There was no significant difference in progression free survival (PFS) between MF and LyP. The median number of Brentuximab Vedotin cycles was 7 (1-19). Skindex-29 scales, showed change in emotion scale and function scale from baseline to EOS, both groups had a decrease, patients with LyP had a larger decrease in emotion score (P = 0.069) and function score (P =0.096) over the course of the study. There was no difference in the symptom scale from baseline to EOS. The patients with LyP had a larger decrease in function score from baseline to EOS. When comparing patients with MF to those with LyP for MDASI, there is no evidence of a difference, from baseline to EOS, in either symptom severity or symptom interference in daily life. In the IQOL when comparing the LyP patients' QOL responses from baseline to EOS, did not show significant difference. Table 1. Change in Skindex-29 scales, by group Skindex Scale MF LYP p-value Change from baseline to end-of-study: N Median Min Max N Median Min Max Emotion 35 -10 -65 35 20 -22.50 -61.94 12.5 0.0698 Symptoms 35 -7.14 -46.43 42.86 20 -10.71 -53.57 28.57 0.4782 Function 35 -2.08 -50.38 27.08 20 -16.29 -44.70 14.58 0.0962 Table 2. Change in MDASI scales, by Diagnosis MDASI Scale Item MF LYP p-value Change from baseline to end-of-study: N Median Mean Std. Dev Range N Median Mean Std. Dev Range Severity 35 0.23 0.18 1.96 (-5.85, 3.15) 21 0.38 0.46 1.61 (-1.69, 5.0) 0.9595 Interference 35 0.17 0.06 3.07 (-9.17, 5.17) 19 0.0 0.11 1.59 (-3.0, 4.67) 0.6764 CONCLUSIONS A significant improvement in emotions and functional part of skindex-29 was observed when comparing patients with MF to patients with LyP. While both groups had a decrease, the patients with LyP had a larger decrease in emotion and function score over the course of the study. Disclosures Duvic: Celgene: Membership on an entity's Board of Directors or advisory committees; Rhizen Pharma: Research Funding; Allos (spectrum): Research Funding; Therakos: Research Funding, Speakers Bureau; Soligenics: Research Funding; Huya Bioscience Int'l: Consultancy; Spatz Foundation: Research Funding; MiRagen Therapeutics: Consultancy; Eisai: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncoceutics: Research Funding; Array Biopharma: Consultancy; Cell Medica Ltd: Consultancy; Tetralogics SHAPE: Research Funding; Innate Pharma: Research Funding; Kyowa Hakko Kirin, Co: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Assessment of Quality of Life in the NCRI Spirit 2 Study Comparing Imatinib with Dasatinib in Patients with Newly-Diagnosed Chronic Phase Chronic Myeloid Leukaemia

Blood ◽

10.1182/blood.v126.23.4024.4024 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4024-4024 ◽

Cited By ~ 2

Author(s):

Alexander M. Labeit ◽

Mhairi Copland ◽

Leanne M. Cork ◽

Corinne A. Hedgley ◽

Letizia Foroni ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

Chronic Phase ◽

Well Being ◽

First Line ◽

Advisory Committees ◽

Significant Difference ◽

Over Time

Abstract Background: Imatinib and dasatinib are established drugs in the first-line treatment of chronic myeloid leukemia (CML). Several studies, including SPIRIT2 have shown that first-line dasatinib (100mg once daily) has a superior complete cytogenetic and major molecular response rate compared to imatinib (400mg once daily), but no significant differences in progression-free or overall survival have been shown in any study. To date, there has been no direct comparison of quality of life (QoL) using generic and cancer-specific instruments for first-line treatment of chronic-phase CML with imatinib and dasatinib. SPIRIT2 (STI571 Prospective International Randomised Trial 2) is the first randomized clinical trial to incorporates generic and cancer-specific QoL measurement for first-line therapy. Methods: Quality of life is a secondary endpoint in the SPIRIT2 trial and has been assessed at baseline, and at 1, 2, 3, 6 and 12 months post trial entry and thereafter annually. The EQ-5D, FACT-G, FACT-BRM and the FACT-TOI have been used as QoL measures in this trial. The FACT-G covers cancer-specific QoL measure dimensions such as physical well-being, functional well-being, social and family well-being, emotional well-being and the FACT-BRM and the FACT-TOI different subsets of them. The QoL scores (EQ-5D, FACT-G, FACT-BRM, FACT-TOI) were calculated at different time points and comparison of the mean scores for both treatment groups was made. Results: A comparison between imatinib and dasatinib shows no significant difference in QoL in generic instruments and also in cancer-specific instruments. EQ-5D was 0.77 and 0.79 at baseline and 0.80 and 0.82 at one year for dasatinib and imatinib, respectively (2-3 basis points increase over 1 year). Similar results were obtained for the FACT-G, FACT-BRM and the FACT-TOI. There was a slight increase for the FACT-G (4-5 basis points), FACT-TOI (3-4 basis points) and FACT-BRM (8-10 basis points) after 1 year for both treatments, but this difference was not significant. The effects on the well-being and the emotional dimensions have been analysed for both drugs and there was no change over time, demonstrating results similar to the imatinib arm of the IRIS trial. Conclusions: Standard dose imatinib and dasatinib are both used as first-line treatments for CML and, despite different side effect profiles, there is no significant difference in QoL using the instruments described here between these two drugs over time. These data will allow the derivation of utility values to contribute to future health economic/technology appraisals. Additional analyses of how generic and cancer-specific measures of different QoL instruments change in CML patients over time in those patients that develop side effects, e.g. fluid retention with imatinib or pleural effusion with dasatinib will be presented. Disclosures Copland: Pfizer: 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; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cork:BMS: Research Funding; Novartis: Research Funding; Roche: Research Funding; Ariad: Research Funding. Hedgley:Ariad: Research Funding; Roche: Research Funding; BMS: Research Funding; Novartis: Research Funding. Gills:Novartis: Research Funding; Ariad: Research Funding; BMS: Research Funding; Roche: Research Funding. Holyoake:Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Bescoby:Roche: Research Funding; Ariad: Research Funding; BMS: Research Funding; Novartis: Research Funding. Pocock:Janssen: Honoraria. Clark:Novartis: Honoraria, Research Funding, Speakers Bureau; Pzifer: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding. O'Brien:Novartis: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Pzifer: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding.

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

Blood ◽

10.1182/blood-2019-131281 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 62-62

Author(s):

Vinita Dhir ◽

Lara Zibdawi ◽

Harminder K Paul ◽

Osvaldo Espin-Garcia ◽

Christine I Chen ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

Indirect Costs ◽

Opportunity Costs ◽

Advisory Committees ◽

Significant Difference ◽

Lost Opportunity ◽

Out Of Pocket Costs

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

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IPH4102; An Anti-KIR3DL2 Monoclonal Antibody in Refractory Sezary Syndrome: Results from a Multicenter Phase 1 Trial

Blood ◽

10.1182/blood-2018-99-118021 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 684-684 ◽

Cited By ~ 1

Author(s):

Martine Bagot ◽

Pierluigi Porcu ◽

Basem M. William ◽

Maxime Battistella ◽

Maarten Vermeer ◽

...

Keyword(s):

Quality Of Life ◽

Monoclonal Antibody ◽

Board Of Directors ◽

Research Funding ◽

Phase 1 ◽

Employment Equity ◽

Advisory Committees ◽

Multicenter Phase ◽

Equity Ownership

Abstract Aims: Sezary Syndrome (SS) is the most aggressive form of cutaneous T cell lymphoma (CTCL), characterized with high blood involvement and expression of Killer cell immunoglobulin like receptor 3DL2 (KIR3DL2). IPH4102 is a first-in-class monoclonal antibody that targets KIR3DL2. Very limited effective treatment options are available for SS patients with refractory disease. We conducted a phase 1 study testing IPH4102 in patients with refractory CTCL. Here we report results from the SS subset. Methods: IPH4102-101 study is a multicenter phase I trial composed of a dose escalation and cohort expansion portions that evaluated IPH4102 in patients with refractory CTCL. Key eligibility criteria included failure of ≥ 2 prior systemic therapies. KIR3DL2 testing was performed for all patients at baseline and at different time points throughout the study. IPH4102 was given Q1w x 4 weeks, followed by Q2w x 10 weeks then Q4w until disease progression or unacceptable toxicity. Primary endpoint is safety. Main 2ry endpoints include best global response (BGR) using the Olsen criteria, progression-free survival (PFS), duration of response (DOR), quality of life (QOL) and biomarker analyses. Results: The study included 35 SS patients, 20 in the dose escalation and 15 in the cohort expansion, with a median age of 70 years (37-90). Median time from initial SS diagnosis to starting IPH4012 was 22.8 months. Nineteen patients (54%) received IPH4102 as ≥ 4th line of systemic therapy and 7 (20%) were previously treated with mogamulizumab. Thirteen patients (37%) had lymph node involvement as per investigator assessment and based on radiological examination while 7 patients (20%) had evidence of large cell transformation. KIR3DL2 expression was observed in either skin or blood in 33 patients (94%) and in both in 28 patients (80%). Most common adverse events (AEs) were asthenia (26%), peripheral edema (26%), and fatigue (23%), which were all grade 1-2. Possibly related grade ≥ 3 AEs were observed in 7 patients (20%), and only 2 patients (6%) stopped treatment for an AE. Table 1 shows BGR and response by compartment. Overall response rate was 42.9% [95% CI: 28.0% - 59.1%], with median time to response of 4.8 months. Median DOR and PFS were 5.6 months [95% CI: 3.2-not reached] and 12.8 months [95% CI: 8.1-not reached], respectively. Mogamulizumab pretreated patients showed BGR, median DOR and PFS of 42.9%, 13.8 and 20.9 months, respectively. Quality of life assessment was performed using the Pruritus VAS score andSkinDex29. Patients with CR, PR or SD showed marked improvement overtime of all evaluated parameters including SkinDex29 global, symptoms, emotional, and functional scores. Biomarker analysis showed progressive decrease in CD4/CD8 ratio in responding patients. The decrease of KIR3DL2+ expressing cells in skin evaluated by immunohistochemistry at week 5 and 14 was able to predict BGR (AUC=0.749, 0.714, respectively). Figure 1 shows reduction in KIR3DL2 expressing cells at week 5 and week 14 in a patient who had PR as BGR. To date, 9 patients are still ongoing treatment. Updated clinical and correlative research analyses will be presented at the meeting. Conclusions: IPH4102 is highly effective in patients with refractory SS. It induces meaningful clinical activity and improves quality of life placing it as an encouraging treatment option for these patients. Further development in SS and other T-cell malignancies is underway. Disclosures Bagot: Actelion: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees. Porcu:Innate Pharma: Consultancy. Khodadoust:Innate Pharma: Research Funding. Sicard:Innate Pharma: Employment, Equity Ownership. Azim:Innate Pharma: Employment, Equity Ownership. Kim:miRagen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Horizon Pharma: Consultancy, Research Funding; Galderma: Research Funding; Tetralogic: Research Funding; Neumedicine: Consultancy, Research Funding; Soligenix: Research Funding; Portola: Research Funding; Forty Seven Inc: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Medivir: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin-Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Similar Quality of Life with 5mg Versus 25mg Lenalidomide Maintenance after First-Line High-Dose Therapy and Autologous Blood Stem Cell Transplantation for Multiple Myeloma: Results of the Lenamain Trial

Blood ◽

10.1182/blood-2018-99-110977 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2003-2003 ◽

Cited By ~ 1

Author(s):

Amelie Boquoi ◽

Aristoteles Giagounidis ◽

Hartmut Goldschmidt ◽

Michael Heinsch ◽

Mathias J Rummel ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

High Dose ◽

Event Free Survival ◽

Advisory Committees ◽

Free Survival ◽

Travel Grant ◽

Grade 3

Abstract Introduction The LenaMain study is a prospective, randomized, open label, multicenter phase III trial which included 188 patients 3 months after first-line high dose treatment and autologous stem cell transplantation (NCT number: NCT00891384). Patients were equally randomized to receive either 25 (n = 94, arm A) or 5 mg (n = 94, arm B) lenalidomide maintenance until disease progression following a uniform 6 months of 25 mg lenalidomide consolidation. Final analysis after follow-up of 46.7 months was presented at ASCO 2018 (#8016) demonstrating an extended event-free survival for arm A (11.8 months, p=0.032) and an about 10% increase of grade 3/4 infections per year as main toxicity. Here we report analysis of quality of life (QoL) data as secondary endpoint of the study. Materials & Methods The EORTC Quality of Life Questionnaire C30 (QLQ-C30) was collected at baseline and then monthly at every new cycle. The Global Health Status/Quality of Life (GHS/QoL) scale, the utility score and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. Results Baseline questionnaire compliance was excellent (95.7%) and declined over time (82%, 76%, 71%, 54%, 49% after consolidation and after year 1, 2, 3 and 4 of maintenance, respectively). At baseline, GHS/QoL (67/67) and utility (0.73/0.72) scores for arm A/B were generally high and did not differ between both arms. The median GHS/QoL change between consolidation baseline and maintenance baseline was -1%. GHS/QoL scores appear constant for both treatment arms at most time points in the first 2 years of maintenance. Relevant improvements ≥ 5 points were observed in 30% of patients while improvements ≥ 15 points were observed in 20% of patients. During the same time a similar percentage of patients had relevant ≥ 5 and ≥15 point deteriorations, with a general tendency for a slight increase at the end of year 2. Notably, a greater number of deteriorations was found in the 5 mg lenalidomide arm. Mean GHS/QoL was constant during maintenance with a slight decrease of <2 over the 1st year, reaching borderline relevance after the 2nd year with a mean change of -6 which was mainly driven by the 5 mg lenalidomide treatment arm (25 mg arm: -4 vs. 5 mg arm: -8). Utility values remained constant during maintenance (change from baseline 0.003, p=0.9 at year 1; 0.02, p=0.7 at year 2) and the overall pattern in the change over time does not appear to show any clear differences between the two treatment arms. Looking at QLQ-C30 subgroup domains after two years of maintenance, we observed a significantly higher change from baseline for diarrhea in the 25 mg lenalidomide arm, which may be a long-term drug-related effect. Conversely, role functioning was also significantly better in patients treated within the 25 mg lenalidomide arm. Other subgroups did not show significant differences after the second year. Overall GHS/QOL scores were not significantly different in patients with CR vs. ≥ vgPR. Similarly, there was no statistical difference in patients on treatment for 1, 2, 3 or 4 years of maintenance or in patients suffering from grade 3/4 adverse events or not. Thus, neither disease activity, nor duration of treatment nor high-grade toxicity biased our results. Conclusion The LenaMain trial shows that maintenance treatment with 25 mg lenalidomide vs. 5 mg significantly prolongs event-free survival. QoL, as secondary objective, was not different between both treatment arms, even showing a trend for improved QoL in the 25 mg lenalidomide treatment arm. Thus, QoL was not governed by the higher rate of infectious toxicity during high-dose lenalidomide maintenance. Disclosures Boquoi: Amgen: Honoraria, Other: Travel grant; Bristol-Myers Squibb: Honoraria; Janssen: Other: Travel grant; Celgene: Other: Travel grant. Goldschmidt:Celgene: Consultancy, Honoraria, Research Funding; Chugai: Honoraria, Research Funding; ArtTempi: Honoraria; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Novartis: Honoraria, Research Funding; Mundipharma: Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Adaptive Biotechnology: Consultancy. Rummel:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Honoraria; Celgene: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Symbio: Honoraria. Kroeger:Sanofi: Honoraria; JAZZ: Honoraria; Novartis: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Riemser: Honoraria, Research Funding. Mai:Celgene: Other: travel grant; Janssen: Honoraria, Other: Travel grant; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding; Onyx: Other: travel grant; Mundipharma: Other: travel grant. Kobbe:Amgen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Celgene: Honoraria, Other: Travel Support, Research Funding. Fenk:Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria, Other: Travel grant, Research Funding; Bristol-Meyers Squibb: Honoraria, Other: travel grant; Janssen: Honoraria.

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

Blood ◽

10.1182/blood-2020-136312 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 8-9

Author(s):

Maria Domenica Cappellini ◽

Ali T. Taher ◽

Antonio Piga ◽

Farrukh Shah ◽

Ersi Voskaridou ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

Publicly Traded ◽

Advisory Committees ◽

Meaningful Improvement ◽

Sf 36 ◽

La Jolla ◽

Domain Scores

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

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Categorized Hematologic Response to Pegcetacoplan Versus Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria: Post Hoc Analysis of Data from a Phase 3 Randomized Trial (PEGASUS)

Blood ◽

10.1182/blood-2020-142166 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 44-45

Author(s):

Antonio Risitano ◽

Ilene C. Weitz ◽

Carlos M. de Castro ◽

Jean-Jacques Kiladjian ◽

Morag Griffin ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Paroxysmal Nocturnal Hemoglobinuria ◽

Response To Treatment ◽

Publicly Traded ◽

Phase 3 ◽

Advisory Committees ◽

Post Hoc Analysis ◽

Hematologic Response ◽

Post Hoc

INTRODUCTION Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, clonal, nonmalignant hematologic disease characterized by complement-mediated red blood cell hemolysis. The current standard of care for patients with PNH is C5 inhibition. Anemia persists in up to ~70% of patients receiving eculizumab and is attributed to persistent intravascular hemolysis (IVH) and mostly to C3-mediated extravascular hemolysis (EVH). Pegcetacoplan is a pegylated pentadecapeptide C3 inhibitor targeting proximal complement to control both IVH and EVH. PEGASUS is a phase 3, open-label, active-comparator controlled study of efficacy and safety of pegcetacoplan versus eculizumab. This post hoc analysis of data from PEGASUS categorized the clinical response to pegcetacoplan or ECU in patients with PNH and hemoglobin <10.5 g/dL (despite stable ECU for ≥3 months). METHODS Hematologic response to treatment was categorized (per Risitano AM, et al. Front Immunol. 2019;10:1157) as complete, major, good, partial, minor, or no response, using number of packed red blood cell transfusions required, hemoglobin level, lactate dehydrogenase (LDH) level, and absolute reticulocyte count (ARC). Complete response: no transfusions required, stable hemoglobin in the normal range, and no evidence of hemolysis (ie, LDH ≤1.5× upper limit of normal, ARC ≤150,000/µL). Major response: no transfusion, normal hemoglobin, but with evidence of hemolysis (LDH >1.5× upper limit of normal and/or ARC >150,000/µL). Good response: no transfusion, but with chronic mild anemia or evidence of hemolysis. Partial response: chronic moderate anemia and/or occasional transfusions (<3 units/6 months). Minor response: regular transfusions required (3-6 units/6 months). No response: regular and frequent transfusions required (>6 units/6 months). Nine patients (6 from the pegcetacoplan arm and 3 from the eculizumab arm) did not readily fit within the existing criteria due to the availability of data at week 16. Although these 9 patients were manually categorized identically by the lead and senior author in a blinded, independent manner, they were not included among these data. RESULTS The intention-to-treat population was comprised of 41 patients randomized to pegcetacoplan and 39 patients randomized to eculizumab. Four patients in the pegcetacoplan arm and 1 patient in the eculizumab arm were not evaluable for analysis due to incomplete data at week 16. Altogether, 61.0% of patients (25/41) in the pegcetacoplan arm have achieved at least a good hematological response, in contrast to 5.1% (2/39) of the eculizumab arm. At week 16, the distribution of response categories was as follows (Figure): in the pegcetacoplan arm and eculizumab arm, respectively, complete responses were 36.6% and 0%, good responses were 24.4% and 5.1%, partial responses were 12.2% and 33.3%, minor responses were 2.4% and 23.1%, and no responses were 0% and 28.2%. The addition of the 9 manually categorized patients did not significantly alter the proportions reported here. Among the factors that may contribute to heterogeneity of hematologic response to treatment are impaired bone marrow function, residual IVH, and residual C3-mediated EVH. Bone marrow failure was ruled out, and no difference in LDH was observed, suggesting that the major factor accounting for the difference between the 2 arms was the prevention of C3-mediated EVH (as confirmed by reduction of C3-opsonization of PNH red blood cells). CONCLUSION In PEGASUS, treatment with pegcetacoplan resulted in a greater proportion of patients with better hematological responses compared to eculizumab. These results further support the concept that proximal complement inhibition, by preventing EVH in addition to controlling IVH, leads to clinical and hematological improvement in the treatment of PNH. Disclosures Risitano: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alnylam: Research Funding; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Samsung: Membership on an entity's Board of Directors or advisory committees; Amyndas: Consultancy; RA pharma: Research Funding; Biocryst: Membership on an entity's Board of Directors or advisory committees; Achillion: Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Pfizer: Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Weitz:Alexion: Consultancy, Honoraria, Speakers Bureau; Apellis: Consultancy, Honoraria. de Castro:Novartis: Honoraria, Other: Steering committee; Alexion: Honoraria, Research Funding; Biocryst: Honoraria, Other: Data monitoring committee; Apellis: Consultancy, Honoraria, Research Funding. Kiladjian:AbbVie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees. Griffin:Biocryst: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals: Honoraria, Other: Conference Support. Hamdani:Apellis: Current Employment, Current equity holder in publicly-traded company. Ajayi:Apellis Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Baver:Apellis: Current Employment, Current equity holder in publicly-traded company. Peffault De Latour:Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Research Funding. OffLabel Disclosure: Pegcetacoplan is an investigational drug for the treatment of paroxysmal nocturnal hemoglobinuria.

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Sustained Improvement in Health-Related Quality of Life in Patients with Hemophilia A with or without Inhibitors Treated with Fitusiran Prophylaxis

Blood ◽

10.1182/blood-2021-147286 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3197-3197

Author(s):

Viridiana Cano ◽

José Bartelt-Hofer ◽

Wenruo Hu ◽

Shauna R. Andersson ◽

Pronabesh Dasmahapatra ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Phase 1 ◽

Publicly Traded ◽

Open Label ◽

Advisory Committees ◽

Open Label Extension ◽

Related Quality

Abstract BACKGROUND Fitusiran is an investigational, subcutaneous (SC), prophylactically administered small interfering RNA (siRNA) therapeutic. It targets antithrombin and restores thrombin generation sufficient to rebalance hemostasis in people with hemophilia A or B, with or without inhibitors. Long-term exposure to fitusiran is being studied in a Phase 1/2, 6-year open-label extension study (NCT02554773) in patients with hemophilia (PwH) A or B with or without inhibitors. Improvement in the health-related quality of life (HRQoL) as measured by Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) total score, and specifically in the physical health domain was previously reported by von Mackensen et al. for PwHA with inhibitors (NCT02554773, N=17, von Mackensen et al. Blood 2020;136(1):23-24). This analysis aimed to present HRQoL changes from baseline to last available measure (LAM), as measured by the Haem-A-QoL total score and domains (filtered by actual treatment exposure following 2 voluntary dosing holds) in PwHA, with or without inhibitors, who continued into the Phase 2 open-label extension study. METHODS Participants who completed the Phase 1 study (NCT02035605) were eligible to participate in Phase 2 long-term exposure study (NCT02554773). All participants received fixed monthly doses of 50 mg (N=9) or 80 mg (N=18) of fitusiran. HRQoL data were collected in 3-month lapse periods. Mean changes from baseline to LAM were calculated for the Haem-A-QoL (total score and domains). RESULTS As of February 2021, 26 severe and 1 moderate PwHA (13 with, 14 without inhibitors) with mean baseline age (SD) 37.3 (9.7) were treated for up to mean (SD) 33.32 (17.06) months. For the total Haem-A-QoL score and each of 10 domains, mean improvements from baseline to LAM (lower scores denoting better HRQoL) were consistently observed in PwHA (except for the sport & leisure domain that was higher in the non-inhibitor group). Mean estimated reductions (SD) in the Haem-A-QoL total score were -8.33 (13.84) and -9.16 (14.55) while that in the physical health domain score were -13.21 (25.07) and -7.14 (22.80), for PwHA with and without inhibitors respectively (Table 1). When comparing Haem-A-QoL domains in inhibitor to non-inhibitor participants, results suggest a modest favorable trend for non-inhibitor patients (greater reductions in 4 vs 6 domains, respectively). CONCLUSIONS Mean improvements in the Haem-A-QoL total scores and 9 out of 10 domains suggest sustained HRQoL improvements in PwHA. Small sample size and outlying results might limit the interpretation. Further research in HRQoL for fitusiran will include a larger population on the new 50 mg every other month dose regimen, and notably Phase III results from NCT03549871 (open-label study in patients switching to fitusiran from previous prophylaxis or bypassing agents) and NCT03754790 (open-label, long-term safety and efficacy study of fitusiran) in various subpopulations. Figure 1 Figure 1. Disclosures Cano: Sanofi Genzyme: Current Employment, Current equity holder in publicly-traded company; Takeda: Ended employment in the past 24 months. Bartelt-Hofer: Sanofi: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company. Hu: Sanofi: Current Employment. Andersson: Sanofi: Current Employment, Current equity holder in publicly-traded company; WEST advisory committee member: Membership on an entity's Board of Directors or advisory committees. Dasmahapatra: Sanofi: Current Employment, Current equity holder in publicly-traded company. Von Mackensen: Biomarin: Speakers Bureau; Novo Nordisk: Consultancy; Sanofi: Consultancy; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; University Medical Centre Hamburg-Eppendorf: Current Employment; CSL Behring: Speakers Bureau; Chugai/Roche: Membership on an entity's Board of Directors or advisory committees.

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Sexuality Challenges, Intimacy, and MPN Symptom Burden: An Analysis By The MPN Quality Of Life International Study Group (MPN-QOL ISG)

Blood ◽

10.1182/blood.v122.21.4088.4088 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4088-4088 ◽

Cited By ~ 5

Author(s):

Holly Lynn Geyer ◽

Amylou C. Dueck ◽

Robyn M. Emanuel ◽

Keith Cannon ◽

Jean-Jacques Kiladjian ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

Multivariate Model ◽

Advisory Committees ◽

Final Multivariate Model ◽

Night Sweats ◽

Sad Mood ◽

And Function

Abstract Background We have previously reported on the high prevalence and severity of challenges with intimacy and sexuality amongst a large international cohort of MPN patients (Emanuel JCO 2012). We sought to further analyze the relationships between issues of intimacy (sexual desire and function), their relationships to MPN disease features, individual MPN symptom prevalence and severity, language, and overall quality of life. Methods Data was collected among an international cohort of patients with MPNs. Subjects completed the BFI, MPN-SAF, and EORTC QLQ-C30 instruments. Surveyed symptoms on the MPN-SAF included the patient’s perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Specifically, the MPN-SAF sexuality item asked about “problems with sexual desire or function”. Total symptom score (TSS) was computed based on 10 symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. Pairwise associations between the MPN-SAF sexuality item and continuous and categorical covariates were investigated using Pearson correlations and analysis of variance/t-tests, respectively. Multivariate regression models were used to investigate impact of groups of covariates on the sexuality item with the final multivariate model selected using forward regression. Results Demographics A total of 1908 MPN patients (essential thrombocythemia=799, polycythemia vera=671, myelofibrosis=432, missing=6) completed the sexuality item. Participants were of typical age (median=60, range 15-94) and gender (female=53%). Overall, 1218 subjects described sexuality related complaints (score >0) with an overall mean symptom score of 3.5 (median=2.0, SD=3.7, range 0-10); 725/1908 (38%) patients had severe sexuality related complaints (score >4). Univariate Analysis Among the QLQ-C30 functioning scales, all domains had similar statistically significant correlations (r=-.26 to -.32, all p<0.001). Among QLQ-C30 symptom scales, all QLQ-C30 symptoms displayed correlations ranging between .08 and .29 (all p<0.001). Among MPN-SAF items, the MPN-SAF sexuality item correlated most significantly with the TSS (r=.41, p<0.001), along with MPN-SAF symptoms (r=.16 to .39; all p<0.001). MPN-SAF sexuality measure significantly differed by anemia (means: absent 3.3, present 4.5; p<0.001), leukopenia (means: absent 3.4, present 4.4; p=0.01), thrombocytopenia (means: absent 3.3, present 4.5; p<0.001), red cell transfusion (means: no 3.5, yes 5.0; p<0.001), MPN subtype (ET mean 3.1, PV mean=3.6, MF mean=4.4; p<0.001) and language (means ranged from 2.4 [Swedish] to 4.6 [Chinese]; p<0.001). MPN-SAF sexuality did not significantly differ by age, gender, prior thrombosis or prior hemorrhage. Multivariate Analysis In a multivariate model of MPN-SAF sexuality containing all QLQ-C30 functioning scales, physical (p=0.001), emotional (p=0.01), cognitive (p=0.005) and social (p=0.002) functioning were all statistically significant. Numerous symptoms were also significant in a multivariate model of MPN-SAF sexuality containing all other MPN-SAF symptoms (all p<0.05; abdominal pain, inactivity, dizziness/vertigo/lightheadedness, insomnia, depression/sad mood, cough, night sweats and overall QOL). The final multivariate model based on forward regression starting with all demographics, clinical variables, and patient-reported QLQ-C30 scales and MPN-SAF items found age, language, QLQ-C30 role functioning and MPN-SAF items (insomnia, depression/sad mood, night sweats and QOL) to be significant (p<0.05). Conclusions Sexuality related complaints have been linked to both physiologic and psychologic origins and are highly prevalent within the MPN population. The results of this study congruently identified close associations between sexuality and function within emotional, cognitive and social domains. Additionally, the correlations of sexuality issues with MPN symptoms and disease features further suggest this item is a key correlate of overall functionality and quality of life. Future investigations into the causative factors and biological correlates of this complaint may assist in addressing this ongoing challenge. Disclosures: Etienne: novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Roy:Novartis, BMS: Honoraria. Harrison:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Birgegard:Vifor Pharma: Honoraria. Mesa:Eli Lilly and Co: Research Funding; Genetech: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Sanofi: Research Funding; NS pharma: Research Funding; Celgene: Research Funding.

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Health Related Quality of Life Results from the Open-Label, Randomized, Phase III Endeavor Trial Evaluating Carfilzomib and Dexamethasone Versus Bortezomib and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.3309.3309 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3309-3309 ◽

Cited By ~ 7

Author(s):

Heinz Ludwig ◽

Philippe Moreau ◽

Meletios A Dimopoulos ◽

Maria-Victoria Mateos ◽

Martin F Kaiser ◽

...

Keyword(s):

Quality Of Life ◽

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Sensitivity Analyses ◽

Life Questionnaire ◽

Advisory Committees ◽

Related Quality ◽

Health Related

Abstract Introduction: The randomized, phase 3 study ENDEAVOR (NCT01568866; N=929) demonstrated a clinically meaningful and statistically significant improvement in progression-free survival for patients with relapsed or refractory multiple myeloma who were treated with carfilzomib and dexamethasone (Kd) versus bortezomib and dexamethasone (Vd; median, 18.7 vs 9.4 months; hazard ratio: 0.53; 95% confidence interval [CI]: 0.44-0.65; P<0.0001) (Dimopoulos et al. Lancet Oncol. 2016;17:27−38). Patient-reported outcomes (PROs) were included as exploratory endpoints in the ENDEAVOR study. Here, we present results of a prespecified analysis of health-related quality of life (HR-QoL) in the ENDEAVOR trial. Methods: HR-QoL was assessed by 3 validated instruments: the European Organization of Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30-item questionnaire (QLQ-C30), the EORTC Quality of Life Questionnaire-multiple myeloma specific 20-item module (QLQ-MY20), and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) "Additional Concerns" neurotoxicity subscale. These instruments were assessed prior to treatment administration on day 1 of cycle 1, and then every 28 days until disease progression, withdrawal of consent, or commencement of other nonstudy anticancer treatment. Due to differing treatment cycle lengths, the PRO assessments coincided across groups every 12 weeks. The primary PRO hypothesis was superiority of Kd over Vd for the Global Health Status/Quality of Life (GHS/QoL) scale of the QLQ-C30. Seven further subscales were prespecified from the QLQ-C30 (fatigue, nausea/vomiting, pain, physical functioning, role functioning) and the QLQ-MY20 (disease symptoms, side effects of treatment). PRO subscales were compared between groups using a restricted maximum likelihood-based mixed model for repeated measures (MMRM). Two sensitivity analyses were performed for the GHS/QoL scale to evaluate the robustness of the MMRM to missing data. Clinical interpretation for the EORTC QLQ-C30 subscales was guided by pre-specifying minimum important differences (MIDs) based on evidence-based guidelines (5 points for the GHS/QoL scale). For the QLQ-MY20 subscales, the standard error of measurement was used as a proxy for the MID. The proportion of patients who had improved (≥5 points) from baseline on the GHS scale was summarized at each coinciding time point. Results: Baseline completion of the QLQ-C30 questionnaire was similar between groups (Kd, 87.7%; Vd, 84.3%). Compliance was high when calculated for all patients expected to provide a questionnaire at each time point (ie, alive and on-study), ranging from 73.1% to 93.9%. Median duration on study treatment was 40 weeks and 27 weeks for Kd and Vd patients, respectively. Using the MMRM model, Kd was associated with statistically significantly higher GHS/QoL scores compared with Vd (p<0.0001). However, the overall treatment difference point estimate of 3.5 (95% CI, 2.0-5.1) did not reach the pre-defined MID. When including the treatment by time interaction (p=0.28) to estimate the treatment difference at timepoints where HR-QoL assessments coincided with day 1 of a cycle, the point estimates increased over time, with the differences at week 60 and 72 reaching clinical significance (5.4 and 5.8, respectively) (Figure). Results from the two sensitivity analyses confirmed findings from the MMRM analysis. Statistically significant benefits were observed in favor of the Kd group for fatigue (P=0.04), pain (P=0.02), side effects (P<0.0001) and NTx subscales (p=0.0002), although these differences did not meet MID thresholds. The proportion of patients reaching a ≥5 point improvement in the GHS scale was numerically higher in the Kd group up to week 48, although the difference between the groups did not reach statistical significance. Conclusions: This analysis of PROs in the ENDEAVOR study demonstrated that Kd was statistically superior to Vd on the QLQ-C30 GHS/QoL scale, with clinically meaningful differences observed at later timepoints but not on average overall. For patients remaining on longer term treatment, the clinical benefits of Kd compared with Vd were associated with better GHS/QOL. Although not meeting MID thresholds, statistically significant benefits were also observed in favor of the Kd group for other aspects of HR-QoL. Disclosures Ludwig: Janssen: Speakers Bureau; BMS: Speakers Bureau; Takeda: Research Funding, Speakers Bureau; Amgen: Research Funding, Speakers Bureau. Moreau:Amgen: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Janssen: Honoraria; BMS: Honoraria; Novartis: Honoraria. Dimopoulos:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis: Consultancy, Honoraria; Celgene: 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; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Mateos:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Glicomimetics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kaiser:BMS: Consultancy, Other: Travel Support; Takeda: Consultancy, Other: Travel Support; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Chugai: Consultancy. Feng:Amgen: Employment, Equity Ownership. Cocks:Amgen: Consultancy; Celgene: Consultancy; BMS: Consultancy; Endomag: Consultancy. Buchanan:Amgen: Employment, Equity Ownership. Weisel:BMS: Consultancy, Honoraria; Novartis: Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Onyx: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

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