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

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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Long Term Treatment and Prevention Of Recurrent VTE In Cancer Patients: Results Of The Canadian Proact Survey

Blood ◽

10.1182/blood.v122.21.5581.5581 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5581-5581

Author(s):

Normand Blais ◽

Charles A. Butts ◽

Mark A. Crowther ◽

Nanette Cox-Kennett ◽

Josée Martineau

Keyword(s):

Clinical Trial ◽

Board Of Directors ◽

Research Funding ◽

Term Treatment ◽

Advisory Committees ◽

Extended Treatment ◽

Treatment And Prevention ◽

Long Term Treatment ◽

Recurrent Vte

Abstract Introduction Cancer associated thrombosis (CAT) is the second leading cause of death in cancer patients after death from cancer. Despite multiple available guidelines for CAT management, there remains variability in treatment practices. In order to gain insight on this variability in Canada, a survey was conducted to identify the perceived importance of managing CAT, identify differences in the pharmacological management of CAT, highlight the main barriers to optimal extended treatment and prevention of recurrent venous thromboembolism (VTE), outline challenges associated with long term treatment adherence, and identify predictors of patient non-adherence. Methods A survey was designed targeting physicians involved in the management of CAT. The questionnaire included queries on physician practice, 37 items related to beliefs and attitudes about extended treatment for prevention of recurrence of VTE, and a 30-item patient-specific profile. Results Responses were obtained from 21 professionals from four Canadian provinces (Nova Scotia, Quebec, Ontario, and Alberta); 76% were hematologists and/or oncologists, 14% were internists and 10% were pharmacists. Community and academic centers were well represented. Specific management profiles were obtained for 131 patients. Most care givers felt that VTE recurrence was an important issue deserving extended therapy for most patients. Although more than 90% believed bleeding and recurrent VTE risk should influence the length of treatment, only 62% believe that VTE recurrence risk should modify the type of treatment and 52% were concerned of the risk of bleeding with long term therapy (≥6 months). 71% of respondents believed patients’ lack of awareness of the risk of recurrent VTE reduces adherence to anticoagulant therapy for extended treatment of VTE. Although 100% of respondents detailed giving verbal patient counseling, only 19% provided written information to patients. 95% stated they assessed compliance verbally; less than 20% used more objective measures (pharmacy records, laboratory monitoring). Participants admitted to using results of clinical trials (95%) more than clinical guidelines (48%) as most felt that the published guidelines contained conflicting recommendations. The main drivers of treatment choice were clinical evidence, efficacy, and personal experience. No respondents indicated they preferred to use oral anticoagulants for extended therapy of CAT and 43% believed that LMWHs should not be used interchangeably. Most (95%) stated they follow-up with patients directly to reassess therapy after 3-6 months of treatment. The patient profile information showed the median age of patients was 62 years and 60% were female. Lung cancer, colon cancer, breast cancer, and lymphoma were the most common tumor sites and accounted for 50% of described cases. Cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) were evenly represented and 82% were symptomatic. Most events were temporally related to cancer therapy (69%), presence of a central venous catheter (18%), and recent surgery (17%). Less than 5% of these cases presented with a contraindication to anticoagulation therapy (severe thrombocytopenia, active bleeding) at CAT diagnosis. Most patients were treated in the outpatient setting. Nonetheless, hospitalization was required in 33% of cases with an average patient stay of 10.8 days. Hospitalized patients were preferentially treated with LMWH (84%) and usually stayed on the same regimen upon discharge (8.3 ± 6.4 months). Long term treatment was largely managed with LMWHs (most frequently dalteparin – 80% of all treated patients) while few were managed with vitamin K antagonists (6%) or novel direct antithrombotics (2%). Anticoagulant therapy for outpatients was prescribed for 9.0 ± 7.7 months after the most recent VTE episode. Conclusion In Canada, CAT is believed to be an important complication of cancer. Extended therapy is indicated for most patients with CAT. Although bleeding risk is perceived as an important reason to modify therapy, contraindications to LMWHs were rare in the reported cases. Uptake of outpatient therapy of CAT is widespread in this country, yet hospitalization is still frequently required at diagnosis and is associated with prolonged inpatient stays. Even if non-adherence to antithrombotic therapy was believed to be rare among patients with CAT, this was rarely rigorously monitored. Disclosures: Blais: Pfizer: Consultancy; Sanofi: Consultancy; Leo: Consultancy. Butts:Pfizer: Consultancy, Honoraria, Speakers Bureau. Crowther:Pfizer: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Merck: Consultancy; Leo Pharma: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; CSL Behring: Speakers Bureau; Boehringer Ingelheim: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Baxter: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Asahi Kasai: Membership on an entity’s Board of Directors or advisory committees; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Viropharma: Membership on an entity’s Board of Directors or advisory committees. Cox-Kennett:Pfizer: honorarium as a speaker Other. Martineau:Pfizer: honorarium as a speaker Other; Boehringer: honorarium as a speaker, honorarium as a speaker Other; Bayer: honorarium as a speaker, honorarium as a speaker Other; Sanofi: honorarium as a speaker and participated in clinical trial, honorarium as a speaker and participated in clinical trial Other; BMS: honorarium as a speaker Other.

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Symptoms, Health-Related Quality of Life, and Tolerability of Loncastuximab Tesirine in Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma

Blood ◽

10.1182/blood-2020-139571 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 3-4

Author(s):

Alexander I. Spira ◽

Lei Chen ◽

Xiaolei Zhou ◽

Ari Gnanasakthy ◽

Luqiang Wang ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

B Cell Lymphoma ◽

Patient Reported Outcome ◽

Publicly Traded ◽

Advisory Committees ◽

Patient Reported ◽

Related Quality ◽

Health Related ◽

Night Sweats

Introduction In the ongoing single-arm, open-label phase 2 ADCT-402-201 study (LOTIS 2, NCT03589469), loncastuximab tesirine has shown substantial antitumor activity with a manageable toxicity profile in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who had failed ≥ 2 prior therapies, including activity in patients with high-risk disease characteristics. The overall response rate was 48.3% (based on positron emission tomography-computed tomography [PET-CT] assessed by independent review according to Lugano response criteria), and the median duration of response was 10.25 months. This analysis examined symptoms, health-related quality of life (HRQoL), and tolerability using validated patient-reported outcome instruments. Methods Enrolled patients aged ≥18 years received loncastuximab tesirine as an intravenous infusion on day 1 of each 3-week treatment cycle. Responders were defined as patients with a best overall response of complete or partial response. Patient-reported symptoms and HRQoL were measured using the Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) and EQ-5D 5 Levels (EQ-5D-5L) instruments at baseline, day 1 of each cycle while patients were treated, and at the end-of-treatment visit. Descriptive statistics for change from baseline scores and percentages of patients with improved, stable, or worsened symptoms were summarized by visit and clinical response. Analysis was conducted using data collected from study initiation (1 August 2018) through 6 April 2020. Results The 145 patients enrolled in this study had a median age of 66 years (range, 23-94). Patients were heavily pretreated, with a median of 3 (range, 2-7) prior systemic therapies. A baseline patient-reported outcome score and at least one post-baseline score were available for 130 patients. Completion rates among patients treated at each visit were ≥ 92% for EQ-5D-5L and ≥ 88% for FACT-Lym up to cycle 9, day 1 (24 weeks). After cycle 9, fewer than 20 patients had patient-reported outcome scores available for analysis. For symptoms assessed in the FACT-Lym lymphoma subscale, pain in certain parts of the body, lumps/swelling, trouble sleeping at night, and fatigue were the most frequently reported symptoms at baseline (34%-59% reported "somewhat" to "very much"). Most patients (≥ 80%) reported "not at all" or "a little bit" at baseline for fever, night sweats, losing weight, itching, and loss of appetite. During the course of treatment, higher percentages of patients reported improvement than worsening for pain and lumps/swelling for the majority of visits. Fever, night sweats, and losing weight did not change for most patients. Itching was the only symptom for which more patients experienced worsening than improvement. For other symptoms, similar percentages of patients reported improvement and worsening. The mean change from baseline in EQ-5D Visual Analog Scale (VAS) score showed a trend of improvement in overall health over time (see figure). The mean VAS change reached the minimally important difference of 7 points at cycle 8, day 1. This improvement was associated with clinical response. When patients were asked how much they were bothered by side effects of treatment, most patients (> 60%) reported "not at all" or "a little bit" for all visits throughout the treatment. Conclusions Results of this analysis suggest that patients who responded to treatment with loncastuximab tesirine generally had stable or improved symptoms and overall HRQoL. The treatment was well tolerated by patients. These findings further support the clinical use of loncastuximab tesirine for the treatment of relapsed or refractory DLBCL. Disclosures Spira: ADCT:Research Funding;Janssen:Consultancy;Incyte:Consultancy;BMS:Consultancy;Merck:Consultancy;Novartis:Consultancy;Takeda:Consultancy;Cardiff Oncology:Research Funding.Chen:ADCT:Current Employment, Current equity holder in publicly-traded company.Zhou:ADCT:Research Funding.Gnanasakthy:ADCT:Research Funding.Wang:ADC Therapeutics America, inc:Current Employment, Current equity holder in publicly-traded company.Ungar:ADC Therapeutics:Current Employment, Current equity holder in publicly-traded company.Curiel:ADCT:Current Employment, Current equity holder in publicly-traded company.Radford:GlaxoSmithKline:Current equity holder in publicly-traded company, Other: Spouse;AstraZeneca:Current equity holder in publicly-traded company, Other: Spouse;Takeda:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Pfizer:Research Funding;ADCT:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;BMS:Consultancy, Honoraria, Speakers Bureau;Novartis:Consultancy, Honoraria;Seattle Genetics:Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.Kahl:AstraZeneca Pharmaceuticals LP:Consultancy, Membership on an entity's Board of Directors or advisory committees;Celgene Corporation:Consultancy;Genentech:Consultancy;Pharmacyclics LLC:Consultancy;Roche Laboratories Inc:Consultancy;BeiGene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen:Consultancy, Membership on an entity's Board of Directors or advisory committees;Acerta:Consultancy, Research Funding;ADC Therapeutics:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;AbbVie:Consultancy.

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Health-Related Quality-of-Life Outcomes in Patients with Classical Hodgkin Lymphoma: A Prospective, Observational Study in US Oncology Practices

Blood ◽

10.1182/blood-2019-123980 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2192-2192

Author(s):

Jakub Svoboda ◽

Philippe Armand ◽

Fiona Taylor ◽

Xiaowu Sun ◽

Alejandro Moreno-Koehler ◽

...

Keyword(s):

Observational Study ◽

Board Of Directors ◽

Research Funding ◽

Advisory Committees ◽

Meaningful Improvement ◽

Patient Reported ◽

Related Quality ◽

Health Related ◽

Treatment Naïve ◽

Multi Agent

Introduction: Classical Hodgkin lymphoma (cHL) is highly curable with front-line multi-agent chemotherapy with or without radiotherapy. The treatment landscape is rapidly evolving, with a continued focus on optimizing available therapies in order to improve outcomes and minimize toxicity. Randomized controlled trials provide valuable insights into new treatments and outcomes; however, real-world data describing treatment effectiveness, safety, and health-related quality of life (HRQoL) are limited. This analysis was conducted to understand patient-reported outcomes (PROs) in patients who were treated for newly diagnosed cHL across a range of academic and community settings. Methods: Study CA209655 is an ongoing, prospective, observational study (NCT02856646) at ~80 US oncology practices with a target enrollment of 500 patients and a planned follow-up of ≤ 5 years. Eligible patients are ≥ 18 years old with histologically confirmed cHL and are treatment naive or within ± 2 weeks of beginning any line of therapy at time of enrollment. HRQoL is a secondary endpoint and evaluated using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire. The FACT-Lym combines a generic cancer-related core consisting of the FACT-General (FACT-G; 27 items) that assesses physical (PWB; 7 items), social/family (SWB; 7 items), emotional (EWB; 6 items), and functional well-being (FWB; 7 items), and a 15-item disease-specific lymphoma subscale (LymS) that assesses lymphoma-specific symptoms. PROs were assessed using questionnaires at baseline (BL), every 3-6 months for ≤ 2 years, and annually thereafter. All patients with BL and ≥ 1 post-BL assessment were included in the PRO analysis. Completion rates and changes from BL scores were evaluated descriptively and analyzed based on published estimates for clinically important differences and individual responder definitions (Hlubocky et al. Lymphoma 2013; Carter et al. Blood 2008; Yost and Eton. Eval Health Prof 2005). High scores indicate better health/functioning for all scales/subscales. Results: Of 278 enrolled patients at data cutoff (Feb 2019), 226 (81%) were treatment naive; for those, the most common index therapy was chemotherapy (n = 210; 93%). The most common index chemotherapies were ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; n = 187, 83%) and AAVD (adriamycin, brentuximab, vinblastine, dacarbazine; n = 10, 5%). Only patients receiving index chemotherapy were included in the full analysis set. In all, 89% (87/210) of patients had BL and ≥ 1 post-BL assessment and were included in the PRO analysis. PRO completion rate at BL was 97% (204/210) and remained > 70% up to 24 months for the expected population. Analysis of PROs was not feasible after 24 months owing to small patient numbers (≤ 10); therefore, PRO analyses were focused on the first 18 months. At BL, mean (SD) scores were: FACT-Lym total, 122 (24); FACT-G, 82 (15); PWB, 21 (6); SWB, 25 (3); EWB, 18 (4); FWB, 18 (6); and LymS, 40 (11). At 3 months there was a deterioration in mean scores from baseline in FACT-G (−3.8) and PWB (−3.0) (Figure A). Clinically meaningful improvement of mean scores was observed starting at 6 months in LymS (+4.4) and at 9 months in FACT-G (+7.1), PWB (+3.1), FWB (+2.8), and FACT-Lym total (+15.6). There were no clinically meaningful improvements in SWB and EWB. Based on individual responder definitions, ≥ 50% of patients had improvements in PWB (Figure B) and FACT-G from 12 months, and FACT-Lym total from 9 months. Conclusions: Initial data from this observational study suggest most patients receive multi-agent cytotoxic chemotherapy as first-line treatment of cHL. Patient-reported PWB initially declined with chemotherapy, but improved with time, and patients had a clinically meaningful improvement in HRQoL by 9 months. The timing of this improvement may be due to discontinuation of chemotherapy due to disease control. Future analyses will evaluate the relationship between improvements in HRQoL and other factors including response, use of immunotherapies versus chemotherapy, and the timing of treatment discontinuation. Study support: Bristol-Myers Squibb. Disclosures Svoboda: Seattle Genetics: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Merck: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy; Celgene: Research Funding; Kyowa: Consultancy; Kite: Consultancy. Armand:Roche: Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka: Research Funding; Sigma Tau: Research Funding; Infinity: Consultancy; Genentech: Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Tensha: Research Funding. Taylor:Adelphi Values: Employment, Other: I am an employee of Adelphi Values, a consulting firm who has received payment from Bristol-Myers Squibb for statistical data analysis in Bristol-Myers Squibb's trials. Sun:Adelphi Values: Employment. Gajavelli:Bristol-Myers Squibb: Employment. Peterson:Bristol-Myers Squibb: Employment, Equity Ownership. Chen:Bristol-Myers Squibb: Employment.

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Improvements in Patient Health-Related Quality of Life (HRQoL) with Clinical Efficacy in Patients Treated with Eltrombopag: Final Results from the Long-Term, Open-Label Extend Study

Blood ◽

10.1182/blood.v128.22.3742.3742 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3742-3742 ◽

Cited By ~ 2

Author(s):

Mansoor N. Saleh ◽

James B. Bussel ◽

Abderrahim Khelif ◽

Paul Burgess ◽

Ali El-Ali ◽

...

Keyword(s):

Platelet Count ◽

Board Of Directors ◽

Research Funding ◽

Physical And Mental Health ◽

Platelet Response ◽

Open Label ◽

Advisory Committees ◽

Related Quality ◽

Health Related ◽

General Physical

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 purpura (cITP) who had previously been enrolled in a pivotal eltrombopag trial. CITP may lead to fatigue and interference with daily activities, and affect patient functioning and experience i.e., health-related quality of life (HRQoL). Objective: To investigate the association between platelet response and HRQoL reported by patients in the EXTEND study, employing widely used and well-validated measures. Methods: Four standard HRQoL instruments were used in this study: SF-36v2 including 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 four 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. HRQoL scores and mean platelet count based on clinical assessments were calculated during time periods post-baseline (BL) to <3 months, ≥3 to <6 months, and at 6-month periods thereafter. Three definitions of response in the absence of rescue therapy (composite of new cITP medication, increased dose of cITP medication from BL, platelet transfusion, and splenectomy) were considered: 1) platelet count ≥30 Gi/L (109/Liter); 2) platelet count ≥50 Gi/L; and 3) platelet count ≥50 Gi/L and > 2 times BL. Generalized estimating equations were used to assess the association between HRQoL over time and clinical response, accounting for within-patient correlation. Covariates included demographic characteristics and BL clinical characteristics (BMI, BL use of cITP medication, prior splenectomy, prior eltrombopag use, and BL platelet count). Results: 302 patients were enrolled in EXTEND. Between 273 and 292 (depending on instrument) had a BL, at least one on-treatment HRQoL assessment, and platelet count information. Baseline platelet count was <30 Gi/L for 69.9% of patients. Median treatment duration was 2.4 years. During treatment, 86.8% of the patients achieved platelet response of platelet count ≥30 Gi/L, 79.8% achieved ≥50 Gi/L, and 75.2% achieved ≥50 Gi/L and 2x BL at least once during the study. All HRQoL instruments had a positive best mean change from BL greater than a minimally important difference of at least half a standard deviation from BL score or an established threshold. All four HRQoL instruments had positive association with the three platelet response definitions. The adjusted mean score increase (signifying improvement) associated with platelet response compared to no response was 0.9-1.3 for SF-36v2 PCS, 0.8-1.3 for SF-36v2 MCS, 1.3-1.9 for MEI-SF, 1.6-2.0 for FACIT-F, and 1.8-2.3 for FACT-Th6 (most p <0.05; Table 1). Conclusion: These data show positive associations between platelet response and HRQoL measurements, especially with SF-36v2 PCS, FACIT-F, and FACT-Th6. Benefits from eltrombopag therapy in increasing platelet counts may carry forward into alleviating fatigue, concerns about bleeding and bruising, as well as enhancing motivation, energy, general physical and mental health status. Disclosures Saleh: GSK: Consultancy, Research Funding, Speakers Bureau. Bussel:Boehringer Ingelheim: Research Funding; Protalex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Physicians Education Resource: Speakers Bureau; Rigel Pharmaceuticals: 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; Prophylix Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; UpToDate: Patents & Royalties; 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; Shionogi: Membership on an entity's Board of Directors or advisory committees; Sysmex: Research Funding; Immunomedics: Research Funding; Genzyme: Research Funding; Cangene: Research Funding; BiologicTx: Research Funding; Ligand: 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. Burgess:Novartis: Employment. El-Ali:Novartis: Employment. Roy:Novartis: Employment. Barghout:Novartis: Consultancy. Duh:Novartis: Research Funding; Abbvie: Consultancy; Allergan: Consultancy; GSK: Research Funding; Bayer: Research Funding; Janssen: Research Funding; Eisai: Research Funding; Pfizer: Research Funding; Medtronic: Research Funding; Takeda: Research Funding; Novo Nordisk: Research Funding; Sanofi: Research Funding; Ariad: Research Funding.

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Tapering Eltrombopag in Patients with Chronic ITP: How Successful Is This and in Whom Does It Work?

Blood ◽

10.1182/blood.v126.23.1054.1054 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1054-1054 ◽

Cited By ~ 5

Author(s):

James B. Bussel ◽

Shah N. Mahmud ◽

Sophie L Brigstocke ◽

Sarah M Torneten

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Term Treatment ◽

Bleeding Events ◽

Advisory Committees ◽

Platelet Counts ◽

Need For Treatment ◽

Chronic Itp ◽

Long Term Treatment

Abstract Background: Thrombopoietin receptor agonists (TPO-RA) eg eltrombopag (Epag), are highly effective treatments of ITP as demonstrated in multiple randomized studies. Studies have shown effective and safe long-term use; toxicity appears tolerable with thromboembolism the most common serious adverse event. An important question is if there will be an indefinite long-term need for treatment with these agents once initiated. The aim of this study is to taper eltrombopag in a single arm study to determine how many and which patients will be able to discontinue treatment over time. It specifically targets patients with adequate counts ie 50-100,000/uL, not waiting for patients whose counts spontaneously increase to high levels and thus indicate that they are being over-dosed. Methods: All patients on eltrombopag at doses of 75 mg daily or less for at least 4 months were offered study entry; only one refused. Initially the study tapered Epag rapidly but then changed to slow tapering over up to 2 years. Patients whose platelet counts were >50,000/uL were tapered at 4 week intervals in 10-20% dose increments. Tapering could be postponed for clinical reasons ie impending procedure or trip, infection skewing count, sports or other physical activity, etc. Analysis was descriptive and t test comparisons used to assess variables associated with successful tapering. Results: Patients were divided into 3 groups: 10 responders (those able to discontinue eltrombopag completely within 2 years, fig 1A), 10 tapering (those still tapering who have reduced their medication but not discontinued it, fig 1B), and 12 non-responders (those who tried and failed to discontinue within 2 years). To complete being a responder required >12 weeks without any ITP treatment, platelet count > 30,000/uL and 20,000/uL more than baseline after the last dose of eltrombopag. Eight of the 10 responders have remained off therapy for more than 1 year with platelet counts consistently > 50,000/uL. No medication was provided in the study. No serious AEs occurred and no serious bleeding events were seen. Fig 1a illustrates the discontinuation of eltrombopag treatment in responders: 4 discontinued within 8 weeks while the longest discontinuation required a full 2 years. Fig 1b shows patients who are tapering eltrombopag but have not reached 2 years by indicating how many are on <70% and <40% of their starting doses; it shows that tapering is typically a slow process but that at least dose reduction can be achieved in many patients even if they do not discontinue their eltrombopag. Table 1 compares means and medians of the 3 groups for a number of clinical variables. While the numbers are small and the results preliminary, it surprisingly shows that patients who have been on eltrombopag longer prior to tapering and those who have received more treatments are more likely to successfully discontinue eltrombopag. In contrast, non-responders failed splenectomy and rituximab more often than did those tapering and responders. Finally AIPF at initiation of study did not predict a successful taper. Summary: A substantial fraction of patients with chronic ITP will be able to successfully taper off eltrombopag; the exact number (somewhere between 10 and 20 of the 32 patients) depends upon the group still tapering. The tapering schedule selected is slow and requires regular monitoring and individualization/flexibility. Even if patients do not fully taper off eltrombopag, they may be able to substantially reduce their dose. We speculate that tapering eltrombopag as outlined here may reduce the toxicity and costs of long-term treatment without diminishing hemostatic efficacy. Table 1. Comparison Table (Responders, Tapering, Non-Responders) Responders (n=10) Tapering (n=10) Non-Responders (n=12) Age (years) (median/average) 29/37.4 11/25.70 21/30.58 Gender (m/f) 3/7 6/4 5/7 Duration ITP (years) (median/average) 8.75/11.95 5.5/17.45 7/8.25 Duration of TPO-RA Therapy (years) (median/average) 5/4.2 5.5/7.45 2.5/3.38 # of prior ITP treatments (median/average) 4.5/5.5 2/2.14 3.5/3.83 # of patients with previous splenectomy 4 0 6 patients with previous Rituximab treatments 5 4 9 Baseline AIPF (tapering counts) (*10E2/uL) (median/average) 81.75/75.5 63/57.43 75/69 Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Bussel: Immunomedics: Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sysmex: Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; BiologicTx: Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Momenta: Membership on an entity's Board of Directors or advisory committees; Symphogen: Membership on an entity's Board of Directors or advisory committees; Protalex: Membership on an entity's Board of Directors or advisory committees.

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Efficacy and Safety of Deferasirox (Exjade®) in Patients with β-Thalassemia Major Treated for up to 5 Years.

Blood ◽

10.1182/blood.v114.22.4063.4063 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4063-4063 ◽

Cited By ~ 4

Author(s):

M. Domenica Cappellini ◽

Silverio Perrotta ◽

Leyla Agaoglu ◽

Yesim Aydinok ◽

Marcello Capra ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Iron Concentration ◽

Term Treatment ◽

Efficacy And Safety ◽

Advisory Committees ◽

Absolute Change ◽

Transfusion Requirements ◽

Long Term Treatment

Abstract Abstract 4063 Poster Board III-998 Background In a large, 1-yr Phase 3 clinical trial, patients (pts) with β-thalassemia (aged ≥2 yrs) were randomized to receive deferasirox (Exjade®) or deferoxamine (DFO), with doses assigned according to baseline liver iron concentration (LIC). Pts completing the 1-yr core were permitted to enter a 4-yr extension; those receiving deferasirox continued on this therapy (deferasirox cohort), while those receiving DFO crossed over to deferasirox (crossover cohort). This analysis evaluates the efficacy and safety of deferasirox over 5 yrs. Methods Based on analyses showing that iron burden and transfusional iron intake need to be considered for appropriate dosing of deferasirox, dose adjustments were permitted in the extension to ensure optimal dosing. Deferasirox dose in the extension was initially based on dose response in the core (deferasirox cohort only) and end-of-core LIC (biopsy or SQUID); subsequent adjustments in steps of 5–10 mg/kg/day were based on serum ferritin (SF) levels and safety markers. Efficacy was assessed by monthly SF levels and LIC at baseline, end of 1-year core and end of study (EOS) (or upon discontinuation). Safety was assessed by incidence and type of adverse events (AEs) and changes in laboratory parameters. Results 296 pts (deferasirox cohort) and 259 pts (crossover cohort) received ≥1 dose of deferasirox; 181 (61%) & 190 (73%) pts from each cohort respectively completed the extension. Most common reasons for discontinuation: consent withdrawal (n=62) and AEs (n=43). Most common AEs leading to discontinuation: increased ALT [n=5], increased transaminases [n=4], glycosuria [n=4]. 2 deaths occurred during the extension in the deferasirox cohort (cardiac failure, cardiomyopathy); 2 in the crossover cohort (cardio-respiratory arrest, road traffic accident); none considered to be related to study drug. Median duration of deferasirox treatment was 61.2 & 48.1 mths in deferasirox & crossover cohorts, respectively. At start of deferasirox, mean LIC was 14.0 ± 9.8 & 10.4 ± 7.6 mg Fe/g dry weight (dw) and median SF was 2211 & 1758 ng/mL in deferasirox and crossover cohorts, respectively. Transfusion requirements at start of deferasirox were comparable; most pts (81% & 83%, respectively) receiving 7–14 mL/kg/mth. Mean deferasirox dose during study: 21.6 ± 6.4 & 23.2 ± 5.9 mg/kg/d (final actual dose: 24.4 ± 8.7 & 27.0 ± 8.0 mg/kg/d) in deferasirox and crossover groups, respectively. Most pts were receiving 15–<35 mg/kg/day at EOS (75% & 78%, respectively); 11% & 17% were receiving ≥35 mg/kg/day. In pts who received at least 5 yrs of deferasirox and at least 4 yrs in the crossover group, mean absolute change in LIC were –5.3 ± 10.1 mg Fe/g dw (n=173; P<0.001) & –2.4 ± 7.6 mg Fe/g dw (n=99; P<0.001) and median absolute change in SF were –775 ng/mL (range: –10164–2572; n=182; P<0.001) & –371 ng/mL (range: –4498–2636; n=151; P<0.001), respectively (Figure). Percentage of pts with LIC<7 mg Fe/g dw increased from 35% to 45% & SF≤1000 ng/mL increased from 12% to 33% from the start of deferasirox to EOS (LIC: EOS, last available value; SF: EOS, average of at most 3 available values after start of deferasirox). Most common drug-related AEs (≥5% overall) after start of deferasirox in deferasirox & crossover cohort, respectively: increased blood creatinine (n=42, 14%; n=20, 8%), nausea (n=28, 10%; n=13, 5%), vomiting (n=18, 6%; n=17, 7%), diarrhea (n=13, 4%; n=15, 6%) & rash (n=17, 6%; n=19, 7%). Frequency of drug-related AEs decreased from year to year. In deferasirox & crossover cohorts, 26 (9%) & 11 (4%) pts had 2 consecutive serum creatinine increases >33% above baseline & upper limit of normal (ULN) & 3 (1%) & 2 (1%) pts had ALT >10 x ULN on 2 consecutive visits, respectively, after start of deferasirox. Conclusions Long-term treatment with deferasirox (for up to 5 yrs) significantly decreased iron burden in β-thalassemia pts aged ≥2 yrs with an increasing percentage of pts achieving therapeutic goals of LIC<7 mg Fe/g dw and SF≤1000 ng/mL. Significant improvements in LIC and SF were also observed after switching from DFO. Deferasirox was well tolerated over this long-term treatment, and the frequency of AEs decreased over time. Disclosures: Cappellini: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genzyme: Membership on an entity's Board of Directors or advisory committees. Perrotta:Novartis: Consultancy, Research Funding. Aydinok:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Vifor International: Membership on an entity's Board of Directors or advisory committees. Piga:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Griffel:Novartis Pharmaceuticals: Employment, Equity Ownership. Lagrone:Novartis Pharmaceuticals: Employment. Clark:Novartis Pharma AG: Employment. Kattamis:Novartis: Consultancy, Honoraria, Speakers Bureau.

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Long Term Safety and Efficacy of Sustained Eculizumab Treatment In Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Blood ◽

10.1182/blood.v116.21.4237.4237 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4237-4237 ◽

Cited By ~ 4

Author(s):

Robert A Brodsky ◽

Carlos de Castro ◽

Hubert Schrezenmeier ◽

Antonio M. Risitano ◽

Joerg Schubert ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Study Drug ◽

Term Treatment ◽

Advisory Committees ◽

Serious Infections ◽

Long Term Treatment ◽

History Of ◽

Terminal Complement

Abstract Abstract 4237 PNH is a chronic, life-threatening, acquired disease associated with deficiency of GPI-anchored complement inhibitory proteins on blood cells. The resulting defective regulation of terminal complement activation is responsible for hemolysis and can lead to thromboembolism (TE), chronic kidney disease (CKD) and pulmonary hypertension. The risk of TE is high, with an observed 6.24 venous TE events per 100 patient years, or approximately 62-fold higher compared to the general population: in fact, TE accounts for 40–67% of PNH related deaths. The effectiveness of anticoagulation (AC) in PNH patients (pts) is uncertain, as AC treated PNH may still experience TE. The terminal complement inhibitor eculizumab reduces intravascular hemolysis rapidly and significantly; it also leads to a reduction in TE events, pulmonary hypertension and improvements in CKD and quality of life. Here, we report on prolonged treatment of PNH patients with eculizumab for safety and sustained patient outcomes. Methods: All pts (N=195) in the PNH eculizumab clinical trials (Pilot (N=11), TRIUMPH (N=87) and SHEPHERD (N=97)) and subsequent Extension studies were assessed for long term safety and efficacy. Median age was 40 yrs, 54% female, 29% had a history of aplastic anemia and 1.5% with history of myelodysplasia. TE was reported in 32% (63/195) of pts prior to eculizumab treatment. There was high adherence to long term treatment; 90% (175/195) of pts completed the parent and extension trials. Results: The median eculizumab treatment duration was 29 mo (1 -66; IQR:23-32m); with a total eculizumab exposure of 474.1 patient-years. Intravascular hemolysis was rapidly reduced in 100% of pts after eculizumab treatment. LDH was reduced from a median of 2,133 U/L (∼10x ULN) at baseline to 310 U/L at 1 month of treatment (P<0.0001) and was sustained at 272U/L at 36 months (P<0.0001). There was an 81% (P<0.0005) reduction in TE events from 52 pre treatment events to 10 trial events using a match time analysis (P<0.0005). Of the 7 (7/195) pts who experienced a TE on drug, 5 had a history of TE and 2 were concomitantly treated with AC. Of pts treated with AC, 59% (58/98) experienced at least 1 TE prior to treatment. In 11 pts who discontinued AC, there were no TE reported with eculizumab treatment during or following AC discontinuation. Prevalence of CKD was reduced from 69% of pts at baseline to 31% (n=29) after 36 months of treatment, consistent with previous results. A fraction of pts still require blood transfusions and a fraction of pts, even without need for blood transfusions, had no significant increase (>1gm/dL) in steady state hemoglobin level over baseline. Eculizumab was well tolerated. Twenty pts (∼10%) did not complete the trial including 9 pts following a reported adverse event (AE). In 16 week follow-up to the 20 pts who discontinued eculizumab treatment, TE was reported in 3 pts, including 1 death. Most AEs (95%) were mild or moderate in severity and 90.8% of adverse events were deemed unrelated to study drug. Frequent AEs were: nasopharyngitis, (40%); headache (37%) and upper respiratory tract infection, (31%). There were 2 cases of meningococcal sepsis and both were successfully treated without sequelae. Serious infections were reported in 21% of pts and 2 pts discontinued therapy due to infections (meningococcal, staphylococcal sepsis: both resolved). Most commonly reported serious infections included pyrexia (4.6%) and viral (3.1%), lower respiratory tract (1.5%) and urinary tract (1.5%) infections. There were 4 patient deaths during treatment. Three deaths were considered not related to study drug and 1 possibly related to study drug by the investigator. Causes of death were progression from myelodysplasia to chronic myelomonocytic leukemia, adenoma progressing to adenocarcinoma, brain herniation following trauma injury, and TE of the small bowel. Conclusion: Long term treatment of PNH pts with eculizumab is associated with a favorable benefit/risk ratio and the clinical benefits demonstrated at earlier timepoints are sustained over 36 months. Improvement in TE and CKD was maintained over 36 months when compared to baseline and previous published data. Considering that thrombosis and CKD have been demonstrated to be significant causes of death in PNH, it is reasonable to expect that eculizumab treatment, by decreasing the risk of thrombosis and improving renal function, may increase the life expectancy of PNH pts. Disclosures: Brodsky: Alexion Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees. de Castro:Alexion Pharmaceuticals, Inc: Speakers Bureau. Schrezenmeier:Alexion Pharmaceuticals, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees. Risitano:Alexion Pharmaceuticals, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schubert:Alexion Pharmaceuticals, Inc: Consultancy, Honoraria. Maciejewski:Alexion Pharmaceuticals, Inc: Consultancy. Duehrsen:Alexion Pharmaceuticals, Inc: Honoraria, Research Funding. Luzzatto:Alexion Pharmaceuticals, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees. Muus:Alexion Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees, Research Funding. Szer:Alexion Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Socié:Alexion Pharmaceuticals, Inc: Consultancy. Hillmen:Alexion Pharmaceuticals, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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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

Blood ◽

10.1182/blood.v118.21.1864.1864 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1864-1864 ◽

Cited By ~ 4

Author(s):

Ruben Niesvizky ◽

Ian W. Flinn ◽

Robert Rifkin ◽

Nashat Gabrail ◽

Veena Charu ◽

...

Keyword(s):

Health Status ◽

Global Health ◽

Board Of Directors ◽

Research Funding ◽

Global Health Status ◽

Linear Mixed Effect Model ◽

Advisory Committees ◽

Mixed Effect ◽

Linear Mixed Effect ◽

Patient Reported

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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Racial Disparities and Their Impact on Knowledge, Behavioral Patterns, and Preferences Towards Participation in Clinical Trials Among Cancer Patients

Blood ◽

10.1182/blood-2020-140390 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 39-40

Author(s):

Meghna Ailawadhi ◽

Mays F Abdulazeez ◽

Leyla Bojanini Molina ◽

Victoria R. Alegria ◽

Taimur Sher ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Board Of Directors ◽

Cancer Patients ◽

Research Funding ◽

Treatment Plan ◽

Term Treatment ◽

Trial Participation ◽

Advisory Committees ◽

Long Term Treatment

Background: Clinical trials are critical to drug development and the formulation of evidence-based guidelines which are essential to providing crucial and often life-saving treatment to cancer patients. Clinical trial participation is very poor in the United States overall, with a dismal representation of racial minorities. While this has been a focus of several efforts focused on education, targeted enrollment etc., there is a lack of understanding of the patient's knowledge and preferences, and how that may be shaping their decision to consider participation in clinical trials. We undertook a patient-reported survey to explore these factors and understand any underlying disparities. Methods: A 15-question paper-based anonymous questionnaire addressing the cancer patient's knowledge about their disease and clinical trials, as well as factors that may shape their understanding of, or may be barriers to their participation in clinical trials was used. This was administered to adult patients with lymphoid malignancies at the Mayo Clinic in Florida. Categorical and continuous variables between white and minority respondents were compared using the Chi-square test and U Mann Whitney with a significance level of 0.05. Results: The survey was completed by 203 cancer patients. Of these, 3 patients did not report race and ethnicity and so responses from 200 patients were included in the final analysis. Of the respondents, 73% (n=146) were white and 27% (n=54) were minorities. Whites were older than minorities, although not statistically significant (median 67 vs. 61.5 yrs, p=0.06). Minority patients had lower education level with 41% having ≤high school education as compared to 16% whites (p<0.001). Majority of white patients (53%) reported their physicians as the highest ranked source of information for cancer vs. 33% minority patients (p=0.01). Other sources of information explored were internet, nurses, family/friends, books/flyers or other patients. A higher number of white patients reported treatment and its side effects to be the topic of most importance to them at the time of cancer diagnosis as compared to minorities (33% vs. 15%, p=0.01). Similarly, prognosis was more important for a higher number of whites than minorities (21% vs. 15%, p=0.03). Understanding of the diagnosis and financial impact were also explored but not found to have any significant difference. Understanding their treatment and long-term treatment plan was the most frequent knowledge gap reported by whites (81%) vs. minorities (54%, p=0.004). Minorities had several knowledge gap areas (understanding the diagnosis, treatment, side effects, long-term treatment plan, financial impact, survival) more evenly distributed. Regarding clinical trials, minorities were more likely to agree that clinical trials were of benefit for patients (42% vs. 28%, p=0.05) and that in a clinical trial the experimental drug always works better than the one it is being compared to (65% vs. 38%, p<0.001). Minority patients were less likely to agree to participating in clinical trials just based on their doctor's recommendation and judgement (83% vs. 93%, p=0.03). A higher number of minority patients felt that pharmaceutical companies have a big influence on the result of a clinical trial (83% vs. 65%, p=0.01). Fear of not benefiting from clinical trials was the reason for not participating among a higher number of whites (36% vs. 19%, p=0.02) while minorities more frequently reported fear of being a guinea pig (22% vs. 14%) and fear of financial burden (17% vs. 8%) although these were not statistically significant. Conclusions: Racial disparities exist at various aspects of cancer-related knowledge resources, gaps and needs. Minorities have more widespread knowledge gaps and depend on more resources for cancer-related knowledge, which may affect their clinical trial participation and preferences. There appears to be mistrust and misinformation guiding minority patient's understanding, leading to more widespread fears of clinical trials. Knowledge gaps and misinformation needs to be addressed in order to achieve higher participation in clinical trials in general, and among minority patients in particular. Disclosures Manochakian: AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Guardant health: Membership on an entity's Board of Directors or advisory committees; Novocure: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Ailawadhi:Phosplatin: Research Funding; Medimmune: Research Funding; BMS: Research Funding; Cellectar: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Takeda: Honoraria; Amgen: Research Funding; Celgene: Honoraria.

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Glasdegib in Addition to Intensive or Non-Intensive Chemotherapy in Patients with Acute Myeloid Leukemia: Safety Analysis of Glasdegib 'On Target' Adverse Events

Blood ◽

10.1182/blood-2018-99-110934 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2732-2732 ◽

Cited By ~ 3

Author(s):

Jorge E. Cortes ◽

Cristina Papayannidis ◽

Catriona Jamieson ◽

Gary J. Schiller ◽

Anna Candoni ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Term Treatment ◽

Employment Equity ◽

Advisory Committees ◽

Long Term Treatment ◽

Equity Ownership ◽

Muscle Spasms ◽

Intensive Group

Abstract Background: Novel agents are frequently added to standard acute myeloid leukemia (AML) treatment backbones yet it is unclear how much additional toxicity this introduces, with the potential for adverse events (AEs) to be caused by the backbone chemotherapy or the disease itself. Glasdegib (PF-04449913) is an investigational, oral small molecule inhibitor of the Hedgehog (Hh) pathway component Smoothened (SMO), currently in clinical development for AML treatment. In a Phase 2 randomized study, addition of glasdegib to low-dose cytarabine (LDAC) improved overall survival (OS) vs LDAC alone and combination therapy was generally well tolerated with minor differences in AE rates vs chemotherapy alone. Here, we analyzed specific 'on target' AEs consistent with inhibition of the SMO component of the Hh pathway to assess impact on overall toxicity. Methods: We pooled safety data from both portions of a Phase 1b + Phase 2 multicenter study (NCT01546038), including AML patients assigned to glasdegib 100 mg QD with LDAC (non-intensive treatment) or with cytarabine/daunorubicin on a 7+3 schedule (intensive treatment) (figure 1). We assessed 'on target' all-causality treatment-emergent AEs of muscle spasms, alopecia, and dysgeusia. We also compared AE onset in defined study time-periods (non-intensive: 0-6, 6-12, or >12 months; intensive: induction, consolidation, maintenance); defining long-term treatment as >12 months for non-intensive and maintenance for intensive. Results: Across studies, 93 patients were enrolled in the non-intensive group and 80 in the intensive group. Here, we focused on patients treated with glasdegib: 89 patients in the non-intensive group and 78 in the intensive group. Table 1 shows baseline characteristics; median treatment duration was 69 days (range 3-1280) and 51 days (10-539), respectively. Rates of treatment discontinuation due to all AEs (inclusive of 'on target' and others), deemed by the investigator to be related to study drug (glasdegib and/or backbone chemotherapy) were similar (non-intensive, 10 patients [11.2%]; intensive, 15 patients [19.2%]). Frequency of muscle spasms was similar for the 2 groups; observed in 19 of the non-intensive group (21.3%) and 18 (23.1%) of the intensive group (table 1), with few grade 3 events (non-intensive 4.5%; intensive 1.3%), and the number of patients who developed muscle spasms (nearly all grade 1) when exposed to long-term treatment was small (4 non-intensive patients; 7 intensive patients) with no cases of rhabdomyolysis. Alopecia was reported for 8 (9.0%) of the non-intensive group and 16 (20.5%) of the intensive group (table 1). Alopecia had earlier time to onset in the intensive arm than in the non-intensive arm (table 1), likely reflecting the concomitant chemotherapy. Alopecia was less frequent during glasdegib maintenance monotherapy (5.3%) in the intensive arm than when given with 7+3 (16.7%). Dysgeusia was similar for the 2 groups, observed in 22 of the non-intensive group (24.7%) and 24 (30.8%) of the intensive group (table 1). For both groups, dysgeusia had similar time to onset and was less common during long-term treatment. The number of patients having a dose modification as a consequence of class-related AEs was low (for non-intensive and intensive, respectively: dose reduction, 5.6% and 2.6%; temporary discontinuation, 4.5% and 2.6%; permanent discontinuation, 1.1% and 2.6%). Conclusions: Glasdegib 'on target' AEs of muscle spasms, alopecia, and dysgeusia were mainly of mild severity, had infrequent dose modifications or permanent discontinuations, and did not appear to impair tolerability of combination treatment. In comparison, muscle spasms and dysgeusia occurred in ≤5% for the LDAC alone arm, and no alopecia was reported. Although muscle spasms and dysgeusia occurred with similar frequency, dysgeusia occurred earlier, for a shorter duration, and was more persistent at the time of discontinuation compared with muscle spasms. Similar safety profiles were observed when combining glasdegib with LDAC or 7+3, suggesting that glasdegib in combination with standard chemotherapy has a manageable safety profile and thus can be an acceptable combination partner in the treatment of AML. Our results are consistent with previously reported safety outcomes for glasdegib as monotherapy in hematologic malignancies. Clinical trials of glasdegib in combination with other standard of care AML agents are ongoing. Disclosures Cortes: Novartis: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Arog: Research Funding. Schiller:Pharmacyclics: Research Funding; Celator/Jazz Pharmaceuticals: Research Funding. Candoni:Pfizer: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Merck SD: Honoraria, Speakers Bureau. Leber:Pfizer Inc: 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; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuko: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Ma:Pfizer Inc: Employment, Equity Ownership. Gallo Stampino:Pfizer Inc: Employment, Equity Ownership. O'Connell:Pfizer Inc: Employment, Equity Ownership. Zeremski:Pfizer Inc: Employment, Equity Ownership. Chan:Pfizer: Employment, Equity Ownership. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees.

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