Digital Life Coaching for Myeloma Patients Undergoing Transplantation

BACKGROUND: Patients undergoing autologous stem cell transplantation (ASCT) for multiple myeloma (MM) face sudden exacerbations of anxiety, insomnia, and other symptoms within the initial weeks following ASCT. Even as these symptoms abate in subsequent months, long-term consequences include post-traumatic stress disorder (Griffith 2020), quality of life (QOL) impairments (El-Jawahri 2016), and chronic reliance on higher-risk medications such as benzodiazepines (Banerjee 2020). These findings are particularly relevant to MM patients given their older age at diagnosis, longer expected post-ASCT survival, and poorer QOL at baseline compared with other cancer patients (Kent 2015). Compared to other integrative interventions in the peri-ASCT setting, life coaching transcends a symptomatic focus while directly addressing the root determinants of impaired QOL. Life coaches work with patients using structured frameworks (Figure 1A) to provide longitudinal support, education, and accountability to meet patient-identified wellness goals. Digital life coaching (DLC) combines the strengths of life coaching with the capabilities of digital health by channeling patient-coach communication through patients' personal phones. Compared to in-person coaching, DLC is location-agnostic and allows patients to work their coaches more conveniently and frequently. DLC is feasible among ASCT survivors (Chen 2016) but has not yet been studied in the active peri-ASCT setting. We are conducting a pilot study of a 16-week DLC subscription to assess its feasibility and effects on QOL during an intensive period spanning from pre-ASCT hospitalization through Day +100 after ASCT. If successful, we plan to then pursue a randomized Phase II study comparing DLC versus usual care in the peri-ASCT setting. METHODS: Our study is registered at clinicaltrials.gov as NCT04432818. We plan to enroll 27 adult patients with MM undergoing first ASCT at our institution. Inclusion criteria include English language proficiency and ownership of a personal cellphone. Notably, neither ownership of a smartphone nor installation of a specific mobile app is required for patient enrollment. Enrolled patients will receive unlimited access to a certified life coach beginning at Day -5 before ASCT; bidirectional communication is encouraged via phone, text, or email. The life coaches will reach out at least once per week to help patients accomplish self-identified goals such as symptom management, stress reduction, and physical activity. Our study's primary endpoint is ongoing patient engagement, defined as least one patient-initiated outreach to their coach during each of four 4-week study subperiods. Our study's secondary endpoints include patient-reported outcome (PRO) assessments of QOL, distress, and sleep disturbances (to be collected using electronic surveys every 1-2 weeks as shown in Figure 1B). Exploratory endpoints include benzodiazepine usage and rates of electronic/phone communication with patients' treatment teams. We will analyze endpoints using descriptive methods, including stratification of secondary & exploratory endpoints by DLC usage and specific 4-week study subperiod. PROGRESS TO DATE: Of 18 approached patients as of the data cutoff (8/1/20), 15 (83%) have expressed interest. Reasons for non-enrollment include skepticism about the value of interactions with coaches who do not themselves have MM. Of the 15 patients who have expressed interest in the study, the median age is 65 (range: 50-81) and all but one patient report owning a personal smartphone. All 6 patients with finalized ASCT hospitalization dates have been enrolled and paired with life coaches. Adherence to weekly electronic PRO assessments has been 100% (n = 9 timepoints) to date, consistent with previous studies (Wood 2013). CONCLUSIONS: Our pilot study is ongoing. Our findings to date suggest that certain MM patients are phone-savvy and would be interested in digital health tools, which will continue to gain prominence in light of the ongoing COVID-19 pandemic. Strengths of DLC include its scalability across institutional lines and its ability to reach patients at home in an integrative manner. Results of this study will inform innovative approaches to support the wellbeing of patients with hematologic malignancies, both in the peri-transplantation setting and beyond. Disclosures Brassil: Pack Health: Current Employment. Patel:Pack Health: Current Employment. Jackson:Pack Health: Current Employment. Wong:Janssen: Research Funding; Roche: Research Funding; Amgen: Consultancy; Sanofi: Membership on an entity's Board of Directors or advisory committees; GSK: Research Funding; Bristol Myers Squibb: Research Funding; Fortis: Research Funding. Wolf:Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Martin:Seattle Genetics: Research Funding; AMGEN: Research Funding; GSK: Consultancy; Sanofi: Research Funding; Janssen: Research Funding. Shah:BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy.

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Clinical Utility and Physician Perceptions of a Digital Platform for Electronic Patient-Reported Outcomes Monitoring in Patients with Hematologic Malignancies in Real-World Practice

Blood ◽

10.1182/blood-2021-146508 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4017-4017

Author(s):

Fabio Efficace ◽

Massimo Breccia ◽

Giovanni Caocci ◽

Leonardo Potenza ◽

Ida Carmosino ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Clinical Utility ◽

Digital Health ◽

Hematologic Malignancies ◽

Advisory Board ◽

Advisory Committees ◽

Patient Reported ◽

Physician Patient Communication ◽

Physician Patient

Abstract Background There is now great interest in using digital health tools to monitor patients' health status in real-world practice. Such tools often include electronic-patient-reported outcome (ePRO) systems in which symptoms questions are included into online interfaces for patient self-reporting, with real-time alerts triggered to the treating physician if severe symptoms or problems are reported. However, there is little information about the clinical utility and user perceptions of these systems, and this is particularly true in the area of hematology. Objectives This study investigates physicians' perceptions of usability and clinical utility of using remote ePROs in routine practice of patients with hematologic malignancies and explored implications in the delivery of patient care. Patients and Methods Remote ePROs are being gathered since December 2020 by the ALLIANCE Digital Health Platform, whose details of the development process have been previously described (Efficace F. et al., JMIR Res Protoc. 2021 Jun 1;10:e25271). Adult patients diagnosed with any hematologic malignancy are eligible to enter the platform, after having provided written informed consent. Aspects related to health-related quality of life (HRQoL), symptoms and medication adherence are assessed via validated PRO measures. The platform allows for real-time graphical presentation to physicians of individual patient symptoms and HRQoL outcomes. Based on a pre-defined algorithm, which includes the presence of clinically important problems and symptoms, the platform triggers automated alerts to the treating haematologists and medical staff. The definition of clinically important problems and symptoms is based on previously defined evidence-based thresholds (Giesinger J. et al., J Clin Epidemiol. 2020 Feb;118:1-8). We asked treating haematologists a feedback about their experience in using the platform, by an ad hoc web-survey consisting of 27 items covering several domains, including: usability and benefits, current use, evaluation of patient health-status, symptoms and adverse events, as well as physician-patient communication. We summarized characteristics of enrolled patients and treating haematologists by proportions, mean, median and range. We also used logistic regression analysis to check the possible association of characteristics of haematologists with survey results. Results Of the 201 patients invited to participate between December 2020 and June 2021 (cut-off date for current analysis), 180 (90%) accepted to enter the ALLIANCE platform, currently activated in 19 centers. The median age of patients was 57 years (range 21-91) and 58% were males. The majority were diagnosed with chronic myeloid leukemia (n=32, 18%) and multiple myeloma (n=31, 17%) and were in stable disease (n=89, 49%). Twenty-three hematologists (44% males) with a median age of 42 years (range 31-63) and an average 17 years (range 5-34) of experience in clinical practice, completed the survey. The majority of physicians (78%) accessed the platform at least once per month (of whom 39% at least once per week), regardless the alerts sent by the system about patients' clinically relevant problems. The frequency of access on a regular basis was also independent of physician sex (p=0.393) and years of experience in clinical practice (p=0.404). Overall, 57% of hematologists discussed often or very often ePROs with their patients, while 83% and 61% deemed this information helpful to better identify symptomatic adverse events (AEs) of grade 1-2 or of grade 3-4, respectively (see figure). Also, 87% and 91% of hematologists found ePROs useful to improve physician-patient communication and the accuracy of documentation of symptomatic AEs (regardless of severity), respectively. Physicians' responses to selected items of the survey are reported in the figure. Conclusions: Current findings support the clinical utility, from the perspective of the treating physician, of integrating ePROs into routine cancer care of patients with hematologic malignancies. Figure 1 Figure 1. Disclosures Efficace: Takeda: Consultancy; Janssen: Consultancy; Abbvie: Consultancy, Other: Grants (to Institution); Amgen: Consultancy, Other: Grants (to Institution). Breccia: Bristol Myers Squibb/Celgene: Honoraria; Pfizer: Honoraria; Abbvie: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Fazio: Janseen: Honoraria. Petrucci: Karyopharm: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board. Rigacci: Merck: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tafuri: Roche: Research Funding; Celgene: Research Funding; Novartis: Research Funding. Siragusa: Novartis, CSL, Behring, Amgen, Novonoridsk, SOBI, Bayer: Consultancy, Honoraria, Speakers Bureau. Patriarca: Incyte: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Argenix: Honoraria. Luppi: Abbvie: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; MSD: Honoraria; Gilead Science: Honoraria, Other: Travel grant; Daiichi-Sankyo: Honoraria; Jazz Pharma: Honoraria. Vignetti: Novartis: Honoraria; Incyte: Honoraria; Amgen: Consultancy, Honoraria.

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Rituximab Plus Three Cycles of Dexamethasone In the Treatment of Immune Thrombocytopenia (ITP): a Pilot Study.

Blood ◽

10.1182/blood.v116.21.3697.3697 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3697-3697

Author(s):

Rebecca Elstrom ◽

Soo Y. Lee ◽

James B. Bussel

Keyword(s):

Platelet Count ◽

Pilot Study ◽

Board Of Directors ◽

Initial Treatment ◽

Research Funding ◽

Advisory Committees ◽

Equity Ownership ◽

Almost All

Abstract Abstract 3697 Introduction: Rituximab has been a useful treatment for patients with ITP; many hundreds of patients have been treated. 30–40% of patients will achieve a complete remission (CR: platelet count >150 × 109/l) with initial treatment and, of this group, the CR will last at least a year in almost all patients. However, emerging data suggests that at least 40% of these patients in CR will relapse between 1 and 3 years from initial treatment suggesting that long-term “cures” only occur in 20% of the initial patients. Therefore it would be desirable if CR's could be achieved in more patients and especially if these would be durable in more than 20%. One approach would be to use rituximab maintenance, however it results in suppression of B-cells for more than 2 years. Dexamethasone has also been used to achieve “cure” in ITP especially in adults at or near diagnosis. Cheng's study suggested that approximately 50% of patients would achieve a long-term response with only one 4-day cycle of high dose (40 mg/day) dexamethasone (N Engl J Med, 2003). A follow up study from GIMEMA suggested that 3–4 cycles of dexamethasone would be better than 1 cycle (Blood, 2007). Finally, Zaja's study suggested that rituximab plus one cycle of dexamethasone was superior to dexamethasone alone with a > 50% CR rate at 6 months (Blood, 2010). Therefore, we elected to perform a pilot study to explore the combination of rituximab with three cycles of dexamethasone at 14 day intervals. Methods: Patients with ITP with platelet counts < 30,000 off therapy and in need of treatment were enrolled. The standard dose (4 infusions of 375mg/m2) rituximab was given on days 1, 8, 15 and 22 and dexamethasone 40 mg (adjusted for size) on days 1–4, 15–18, and 29–32. Results: Fourteen patients between the ages of 4 and 53 years with ITP were treated with rituximab and dexamethasone (R&D) (Table 1). All had received previous steroid therapy as well as other treatments. The median platelet count was 40,000 at initiation of rituximab (range 7,000-230,000); several patients with low counts started with dexamethasone prior to initiating Rituximab to sustain their counts during initial treatment. Patients received rituximab weekly for between 2 and 4 doses and dexamethasone for either 2 or 3 courses at intervals between 1 and 8 weeks (median 2 week intervals). A summary of the results is shown in table 2 demonstrating short-lived platelet increases in response to dexamethasone in almost all patients. With short follow up, there were 7 CR's, 3 PR's and 4 NR's. If this was divided by duration of ITP prior to R&D, there were 4 CR's and 1 NR for ≤ 12 months and 3 CR, 3 PR, and 3 NR for > 12 months. More of the children who were treated had chronic disease than did adults explaining their apparently poorer response. Observed toxicities included hyperglycemia, grade 1 and 2 liver function abnormalities, weight gain, and 1 episode of colitis requiring hospitalization. Three patients opted to skip the third cycle of dexamethasone. Conclusion: A regimen of rituximab + 2–3 courses of dexamethasone is active in patients with pretreated ITP with appreciable but usually manageable toxicity. It appears to yield superior results if administered to patients within one year of diagnosis. This combination merits further exploration in a prospective clinical trial. Disclosures: Bussel: Portola: Consultancy; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Equity Ownership, 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; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc.: Membership on an entity's Board of Directors or advisory committees; Cangene: Research Funding; Genzyme: Research Funding.

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

Blood ◽

10.1182/blood-2019-129269 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5764-5764 ◽

Cited By ~ 1

Author(s):

Rodney H Falk ◽

Morie A Gertz ◽

Merrill D Benson ◽

Gustavo Buchele ◽

Michela Brambatti ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Parent Compound ◽

Controlled Study ◽

Efficacy And Safety ◽

Phase 3 ◽

Advisory Committees ◽

Study Visit ◽

Clinical Events ◽

Patient Reported

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

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

Blood ◽

10.1182/blood.v130.suppl_1.973.973 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 973-973

Author(s):

Michael U. Callaghan ◽

Patrick C. Hines ◽

Debra D Pittman ◽

David Beidler ◽

Denis Rybin ◽

...

Keyword(s):

Clinical Trials ◽

Board Of Directors ◽

Research Funding ◽

Patient Reported Outcomes ◽

Clinical Laboratory ◽

Advisory Committees ◽

Pain Scores ◽

Patient Reported ◽

Platelet Aggregates ◽

At Home

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

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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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Sleep Disturbance Among Individuals with Multiple Myeloma: The Interplay between Physical and Psychosocial Symptoms

Blood ◽

10.1182/blood-2018-99-113397 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4830-4830

Author(s):

Julie Olson ◽

Shauna McManus ◽

Melissa F. Miller ◽

Thomas W. LeBlanc ◽

Eva Yuen ◽

...

Keyword(s):

Sleep Disturbance ◽

Board Of Directors ◽

Research Funding ◽

Symptom Burden ◽

Physical Symptom ◽

Physical Symptoms ◽

Psychosocial Distress ◽

Advisory Committees ◽

Depression Subscale ◽

Patient Reported

Abstract Background: As long-term survival rates for multiple myeloma (MM) improve, and patients receive more prolonged courses of treatment, individuals living with MM experience cumulative physical symptom burden and psychosocial distress. However, the relationship between physical and psychosocial symptoms in MM remains poorly understood. Sleep disturbance is a common symptom in MM, and has been linked to both physical symptoms and psychological issues, including fatigue, mood disturbance, and decreased physical function. We test our hypothesis that the interaction between physical and psychosocial health is associated with sleep disturbance in a national sample of MM patients. Methods: Using data from the Cancer Support Community's Cancer Experience Registry®, our analytic sample includes 288 participants who reported MM as their primary diagnosis and completed the Patient-Reported Outcomes Measurement Information System (PROMIS-29v1.0), a self-reported measure of functioning in 7 domains (depression, anxiety, satisfaction with social roles, physical function, pain interference, fatigue, and sleep disturbance). The dependent variable in all analyses was the continuous T-score on the PROMIS sleep disturbance subscale. Our independent variables include psychosocial distress, operationalized using a continuous T-score on the PROMIS depression subscale, and physical symptom burden, which we calculate using patient-reported data on daily interference from peripheral neuropathy, bone pain, GI toxicity, and infection. Using multivariate regression, we predicted sleep disturbance from psychosocial distress and physical symptom burden, controlling for gender, age, race/ethnicity, time since diagnosis, and a dichotomous indicator of ever having received a stem cell transplant. Next, we calculated an interaction term (physical symptom burden X distress) to evaluate whether sleep disturbance is associated with the concurrent presentation of physical and psychosocial symptoms. Results: Overall, 17% of our sample reported levels of psychosocial distress that were more than one standard deviation above the national average on the PROMIS depression subscale. Approximately 6% fell above the national average for sleep disturbance. Our sample was 54% female, 86% White, and averaged 63 years of age (SD = 9), with a mean time since diagnosis of 4 years. Results of the multivariate analyses revealed that physical symptom burden and psychosocial distress were independently and positively associated with sleep disturbance (p < .05). In other words, greater physical symptom burden and higher levels of distress were linked to elevated sleep disturbance, after controlling for sociodemographic and clinical variables. Additionally, the interaction between physical symptom burden and psychosocial distress on sleep disturbance was statistically significant (p = .05). That is, the degree to which MM symptom burden is linked to sleep disturbance depends on psychological distress. Specifically, sleep disturbance is intensified for individuals living with MM when physical symptom burden is accompanied by distress. Overall, our results point to the important interplay of physical and psychological health for sleep. Conclusion: In the presence of physical symptom burden, sleep disturbance is exacerbated for individuals with psychosocial distress. Clinicians should consider screening for and addressing psychosocial distress when addressing sleep disturbance, particularly among those patients who also report physical symptoms. Indeed, assessing both physical and psychosocial symptoms will inform more comprehensive symptom management. We recommend referrals to inter-disciplinary teams with specialists that address both physical and psychosocial concerns. Disclosures Birhiray: Genomic Health: Patents & Royalties; Norvatis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eli-Lilly: Speakers Bureau; Alexion: Consultancy; Takeda: Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Tessaro: Speakers Bureau; Pharmacyclics: Speakers Bureau; AstraZeneca: Speakers Bureau; Pfizer: Speakers Bureau; Excelis: Speakers Bureau; Puma: Research Funding, Speakers Bureau; Clovis Oncology: Speakers Bureau; Sanofi Oncology: Speakers Bureau; Incyte: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Helsinn: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

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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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Predictors for Improvement in Patient-Reported Outcomes: Post-Hoc Analysis of a Phase 3 Randomized, Open-Label Study of Eculizumab and Ravulizumab in Complement Inhibitor-Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Blood ◽

10.1182/blood-2021-144554 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2196-2196

Author(s):

Hubert Schrezenmeier ◽

Austin G. Kulasekararaj ◽

Lindsay Mitchell ◽

Regis Peffault De Latour ◽

Timothy Devos ◽

...

Keyword(s):

Rare Disease ◽

Board Of Directors ◽

Clinical Outcomes ◽

Research Funding ◽

Advisory Committees ◽

Clinical Variables ◽

Patient Reported ◽

Eortc Qlq C30 ◽

Eortc Qlq ◽

Support Research

Abstract Background : Patients with PNH have uncontrolled terminal complement activation that can lead to thrombosis, organ damage, intravascular hemolysis (IVH), and clinical sequelae. It is also associated with debilitating patient-reported outcomes (PROs), such as fatigue, dyspnea, and pain that contribute to a poor quality of life (QoL). Whilst it is known that improvements in clinical outcomes are associated with C5 inhibitor (C5i) therapy in patients with PNH, evidence characterizing the relationship between clinical outcomes and fatigue or QoL are limited. Understanding key clinical drivers of improvements in QoL and fatigue during complement C5i therapy is vital for developing appropriate management strategies. Aims : To assess the relationship between clinical outcomes with fatigue and QoL, as measured by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Global Health (EORTC QLQ-C30 GH), in patients with PNH receiving C5i therapy. Methods : Post-hoc analyses were performed using data from a 26-week data cut of a randomized phase 3 study (NCT02946463) that assessed ravulizumab and eculizumab in complement inhibitor-naïve patients with PNH and high disease activity (defined as a lactate dehydrogenase [LDH] level ≥ 1.5 × upper limit of normal [ULN; 246 U/L] and ≥ 1 sign or symptom of PNH at screening). The PRO measures (PROMs) used were FACIT-F and EORTC QLQ-C30 GH. Clinical variables included LDH, hemoglobin (Hb), bone marrow disorders, transfusions, and hematological parameters such as reticulocyte, platelet, and neutrophil counts. Multivariable regressions were performed separately for each PROM to assess the effect of clinical variables on PROM score changes from baseline to day 183, controlling for demographic characteristics and baseline PROM scores. Multicollinearity between covariates was tested in each regression model and removed when present. Results : Data for 121 and 125 patients with PNH treated with eculizumab or ravulizumab were included, respectively. Trial data showed that reduced LDH levels at day 183 were associated with improvements in FACIT-F in both treatment groups; however, no equivalent association was observed with Hb levels (Figure 1). In the regression analyses, significant predictors of FACIT-F improvement included reductions in LDH levels from baseline to day 183 (p = 0.0024) and the interaction of both achieving a LDH level ≤ 1.5 × ULN by day 183 and improvements in Hb from baseline (p = 0.0285). Similarly, significant predictors of EORTC QLQ-C30 GH improvement also included reductions in LDH levels from baseline to day 183 (p < 0.0001) and an increase in Hb from baseline to day 183 after receiving a transfusion during the study period (p = 0.02). However, Hb as a main effect, whether as an improvement in Hb levels from baseline to day 183, or Hb values at baseline, were not statistically significant predictors of improvement in either PROM at day 183. Conclusions : In this analysis, key clinical drivers of improvement in PROMs were determined among patients with PNH receiving C5i therapy. When multiple clinical variables were considered, reductions in LDH were one of the strongest predictors of improvements in fatigue and QoL. Increases in Hb levels from baseline were only a significant predictor of improvement in FACIT-F for patients who had attained LDH level ≤ 1.5 × ULN at day 183, highlighting the importance of controlling IVH in patients with PNH. Finally, these results suggest that Hb alone is not a strong predictor of improvements of fatigue and QoL in this disease setting. Figure 1 Figure 1. Disclosures Schrezenmeier: Alexion, AstraZeneca Rare Disease: Honoraria, Other: Travel support, Research Funding; Apellis: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Novartis: Honoraria. Kulasekararaj: F. Hoffmann-La Roche Ltd.: Consultancy, Honoraria, Speakers Bureau; Apellis: Consultancy; Akari: Consultancy, Honoraria, Speakers Bureau; Biocryst: Consultancy, Honoraria, Speakers Bureau; Achilleon: Consultancy, Honoraria, Speakers Bureau; Alexion: Consultancy, Honoraria, Speakers Bureau; Ra Pharma: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Alexion, AstraZeneca Rare Disease Inc.: Consultancy, Honoraria, Other: Travel support. Mitchell: Alexion, AstraZeneca Rare Disease Inc.: Honoraria. Peffault De Latour: Jazz Pharmaceuticals: Honoraria; Amgen: Consultancy, Other, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Devos: AbbVie: Consultancy; Alexion, AstraZeneca Rare Disease Inc.: Consultancy; Incyte: Consultancy; Novartis: Consultancy; Bristol Myers Squibb - Celegene: Consultancy. Okamoto: Alexion, AstraZeneca Rare Disease Inc.: Honoraria, Research Funding. Wells: Alexion, AstraZeneca Rare Disease Inc.: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Johnston: Broadstreet HEOR: Current Employment. Popoff: Broadstreet HEOR: Current Employment. Cheung: Broadstreet HEOR: Current Employment. Wang: Alexion, AstraZeneca Rare Disease Inc.: Current Employment. Gustovic: Alexion, AstraZeneca Rare Disease: Current Employment. Wang: Alexion, AstraZeneca Rare Disease: Current Employment. Tomazos: Alexion, AstraZeneca Rare Disease: Current Employment. Patel: Alexion, AstraZeneca Rare Disease Inc.: Current Employment. Lee: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Idelalisib Rapidly Improves Platelets Function in Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽

10.1182/blood.v128.22.5566.5566 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5566-5566

Author(s):

Gianluigi Reda ◽

Ramona Cassin ◽

Andrea Artoni ◽

Anna Lecchi ◽

Bruno Fattizzo ◽

...

Keyword(s):

Platelet Count ◽

Platelet Aggregation ◽

Pilot Study ◽

Board Of Directors ◽

Research Funding ◽

Bleeding Risk ◽

Bleeding Tendency ◽

Advisory Committees ◽

Coagulation Tests ◽

Haematological Remission

Abstract INTRODUCTION Platelet function has never been studied systematically in patients with CLL. Novel drugs are now available for CLL treatment that may impact on platelet functions. Fifty per cent of patients treated with Ibrutinib suffered from minor bleedings and only 5% from major bleedings, partly caused by the drug driven inhibition of platelet glycoprotein VI signaling. No data on bleeding tendency has yet emerged on patient treated with Idelalisib, the first specific inhibitor of PI3K δ p110 approved for the treatment of relapsed/refractory CLL or for patients with del17p or TP53 as first line therapy. In animal models a reduction of p110δ on platelets (PLT) does not increase bleeding, causing only a slight reduction of platelet aggregation and activation. Knowledge about potential bleeding complications associated with the use of small molecules may be relevant in older patients and those at increased bleeding risk due to concomitant therapies. PATIENTS AND METHODS Ten patients with CLL (M/F: 6/4; median age: 71 years, range 47-82) who started therapy with Idelalisib were enrolled in a prospective observational pilot study. The Bleeding Severity Score (BSS), a validated questionnaire, was administrated to patients to estimate bleeding before and during idelalisib therapy. All patients underwent coagulation tests and platelet aggregation/secretion studies with different aggregating agents before starting therapy with Idelalisib, after 28 + 7 days and after 3 months. Patients with a platelet count less than 80.000/mm3, in antiplatelet or anticoagulant therapy, with recent use (within 7 days) of NSAIDs and a diagnosis of hereditary thrombocytopenia/pathy were excluded. We defined complete haematological remission (CHR) as Hb more than 11g/dl, PLT more than 100.000/mm3, lymphocyte less than 5.000/mm3 and partial haematological remission (PHR) as a response not fulfilling criteria for CHR. RESULTS No cases of hemorrhagic complications or increased bleeding tendency were observed in patients with CLL and no patients had a pathologic BSS (>5) at enrolment. All patients had coagulation tests within normal limits at baseline and after 28 days. Platelet count was below 100.000/mm3 in 5 patients. In 9 out of 10 patients platelet aggregation was pathological with at least 2 of the 4 aggregating agents tested. Platelet secretion before initiation of treatment with Idelalisib was particularly impaired with ADP (8/10 patients), while was pathological with collagen, a strong agonist, in only 2 patients. In 8 patients intraplatelet ATP/ADP ratio was pathological, as observed in delta storage pool disease. After 28 days of treatment 4 of 10 patients were in CHR and 3 in PHR. Platelets count was still below 100.000/mm3 in 2 subjects. At 28 days in 5 out of the 9 patients with pathological baseline test, platelet aggregation improved, while 3 remained unchanged and in one worsened. Even ADP secretion normalized in 4 patients. ATP/ADP ratio did not significantly change. At three months 7 patients reached CR and 2 reached PR. At three months platelets count was still below 100000/mm3 in 2 patients. In 3 patients platelet aggregation further ameliorated. CONCLUSIONS In this pilot study, treatment with idelalisib improved platelet aggregation tests in most of the CLL patients who presented a pathological test before starting therapy. It's unlikely that the drug has a direct effect on platelets, given their low expression of PI3Kδ; therefore our results are probably due to the rapid idealisib effect on CLL clone. Based on these preliminary data, Idelalisib seems to be safe in patients with an increased bleeding risk. Disclosures Reda: Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Research Funding. Peyvandi:Alexion: Other: research funding paid to Luigi Villa Foundation, Research Funding; Ablynx: Membership on an entity's Board of Directors or advisory committees, Other: research funding paid to Luigi Villa Foundation, Research Funding; CSL Behring: Speakers Bureau; Biotest: Other: research funding paid to Luigi Villa Foundation, Research Funding, Speakers Bureau; Octapharma: Consultancy; Kedrion Biopharma: Consultancy, Other: research funding paid to Luigi Villa Foundation, Research Funding; LFB: Consultancy; Grifols: Speakers Bureau; Novo Nordisk: Other: research funding paid to Luigi Villa Foundation, Research Funding, Speakers Bureau; SOBI: Speakers Bureau; Bayer: Speakers Bureau.

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Patient-Reported Quality of Life before and after Stopping Treatment in the ENESTfreedom Trial of Treatment-Free Remission for Patients with Chronic Myeloid Leukemia in Chronic Phase

Blood ◽

10.1182/blood.v128.22.3066.3066 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3066-3066 ◽

Cited By ~ 4

Author(s):

Andreas Hochhaus ◽

Maria Teresa Gómez Casares ◽

Jesper Stentoft ◽

Eibhlin Conneally ◽

Valentin García-Gutiérrez ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Chronic Phase ◽

Molecular Response ◽

Advisory Committees ◽

Patient Reported ◽

Consolidation Phase ◽

Stopping Treatment ◽

Anxiety Depression ◽

Eq Vas

Abstract Background: Many patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) achieve a sustained deep molecular response (DMR) with frontline nilotinib (NIL) therapy. ENESTfreedom (NCT01784068) is an ongoing phase 2 study evaluating the potential for such pts to stop treatment and remain in treatment-free remission (TFR). Initial results from ENESTfreedom showed that 51.6% of pts who attempted TFR remained off treatment without loss of major molecular response (MMR [BCR-ABL1 ≤ 0.1% on the International Scale, BCR-ABL1IS]) at 48 weeks. Despite the enrollment of pts with established tolerance of NIL, the frequency of adverse events (AEs) decreased during the first 48 weeks of TFR compared with the year prior to stopping treatment (65.8% vs 83.2%, respectively), while AEs related to musculoskeletal pain were more common during TFR (24.7% vs 16.3%, respectively). The quality of life (QOL) of tyrosine kinase inhibitor-treated pts has gained increasing interest in recent years. To evaluate the impact of TFR on QOL, we analyzed patient-reported outcomes prior to and during TFR. Methods: Pts with CML-CP and ≥ 2 years of frontline NIL therapy (400 to 600 mg/day for the previous ≥ 1 year) who achieved MR4.5 (BCR-ABL1IS ≤ 0.0032%) on NIL were enrolled and entered a 1-year consolidation phase, during which they continued NIL with RQ-PCR assessments every 12 weeks. Pts with sustained DMR during the consolidation phase (no assessment worse than MR4 [BCR-ABL1IS ≤ 0.01%], ≤ 2 assessments between MR4 and MR4.5, and MR4.5 in the last assessment) entered the TFR phase and stopped treatment. Pts with loss of MMR during the TFR phase reinitiated NIL treatment (reinitiation phase). At specified time points, pts completed the MD Anderson Symptom Inventory for CML (MDASI-CML, in which pts rate the levels of severity and interference with daily life for a defined set of symptoms on a scale from 0 to 10, with 0 indicating the lowest severity/interference). At each time point, pts also completed the EQ-5D-5L questionnaire, in which they report the presence/absence and severity (slight, moderate, severe, or extreme) of problems related to mobility, self-care, usual activities, anxiety/depression, and pain/discomfort and rank their overall level of health from 0 to 100 using the EQ VAS scale, with 0 indicating the poorest level of health. Results: Among 215 pts enrolled, 190 remained in sustained DMR during the consolidation phase and entered the TFR phase. Mean MDASI-CML severity and interference scores and EQ VAS scores, respectively, among pts who completed each questionnaire were 1.4, 1.7, and 80.5 at week 48 of the consolidation phase; 1.1, 1.3, and 81.1 at week 12 of the TFR phase; and 1.2, 1.4, and 81.4 at week 48 of the TFR phase (Table). Among pts who sustained TFR and who had scores at both week 48 of the consolidation phase and week 12 or 48 of the TFR phase, no impact of stopping treatment on MDASI-CML or EQ VAS scores was detected. Among evaluable pts who lost MMR during the TFR phase and reinitiated NIL, mean scores at 24 weeks after treatment reinitiation were 1.3 (MDASI-CML severity), 1.5 (MDASI-CML interference), and 77.8 (EQ VAS). Among pts evaluable at both week 48 of the consolidation phase and week 24 of the reinitiation phase, mean scores were similar at both time points. Among pts who completed the EQ-5D-5L questionnaire, the proportions reporting problems (of any severity) at week 48 of the consolidation phase, weeks 12 and 48 of the TFR phase, and week 24 of the reinitiation phase tended to be similar. The proportion of pts reporting problems with anxiety/depression was lowest during the reinitiation phase (Table). Conclusion: Minimal changes in patient-reported outcomes were observed after stopping treatment. This may be related to pts having a relatively high QOL prior to stopping treatment, given that they had tolerated ≥ 2 years of NIL prior to enrollment. These data suggest that the higher frequency of musculoskeletal pain-related AEs in the TFR phase did not substantially impact pts' QOL; however, only a subset of pts were evaluable for changes in reported outcomes over time. Although many pts have fears about TFR, reported levels of anxiety/depression were similar before and after stopping treatment but decreased among pts who reinitiated treatment. Disclosures Hochhaus: BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding. Casares:Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Ariad: Consultancy, Speakers Bureau. Stentoft:Pfizer: Research Funding; Ariad: Research Funding; Bristol-Myers-Squibb: Research Funding; Novartis: Research Funding. Conneally:Novartis: 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; Pfizer: 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. García-Gutiérrez:Ariad: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Gattermann:Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Other: travel, accomodation expenses, Research Funding. Wiktor-Jedrzejczak:Sandoz: Consultancy; BMS: Research Funding; Novartis: Consultancy, Research Funding; Janssen-Cilag: Consultancy; Angelini: Consultancy; Novartis: Consultancy, Research Funding; Celgene: Consultancy; Amgen Inc.: Research Funding. Le Coutre:Ariad: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Other: travel, accomodations, expenses; Novartis: Consultancy, Honoraria, Other: travel, accomocations, expenses, Research Funding. Saussele:ARIAD: Honoraria; Novartis: Honoraria, Other: Travel grants, Research Funding; Pfizer: Honoraria, Other: Travel grants; BMS: Honoraria, Other: Travel grants, Research Funding. Giles:Novartis: Consultancy, Research Funding. Radich:Ariad: Consultancy; BMS: Consultancy; Novartis: Consultancy, Research Funding. Ross:BMS: Honoraria; Novartis Pharmaceuticals: Honoraria, Research Funding. Menssen:Novartis Pharma AG: Employment. Deng:Novartis Phamaceuticals Corp.: Employment. Brandt:Novartis: Employment. Gnanasakthy:Novartis: Consultancy, Equity Ownership, Research Funding. Bedoucha:Novartis: Employment. Saglio:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Ariad: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria.

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