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

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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Safety and Efficacy of Romiplostim in over 200 Children with Immune Thrombocytopenia (ITP): Results of an Integrated Database of 5 Clinical Trials

Blood ◽

10.1182/blood-2018-99-109763 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2428-2428 ◽

Cited By ~ 1

Author(s):

Michael D. Tarantino ◽

Jenny M. Despotovic ◽

John Roy ◽

John Grainger ◽

Nichola Cooper ◽

...

Keyword(s):

Bone Marrow ◽

Platelet Count ◽

Board Of Directors ◽

Research Funding ◽

Platelet Response ◽

Open Label ◽

Advisory Committees ◽

Baseline Platelet Count ◽

Platelet Counts

Abstract Background: Romiplostim is approved globally for use in adults with ITP and in the EU for children with ITP. More comprehensive data are needed on the use of romiplostim in children with ITP. Objective: To examine the safety and efficacy of romiplostim in trials in children with ITP. Methods: Data were combined from 5 romiplostim trials in children with ITP, both placebo-controlled (a phase 1/2 and a phase 3 trial) and open-label (a 3-year trial and 2 extension trials); trial data have been reported previously (Bussel Blood 2011, Bussel PBC 2014, Tarantino Lancet 2016, Tarantino ASH 2017, Grainger ASH 2017). Platelet counts in the 4 weeks after use of rescue medication were excluded from analyses. Descriptive statistics were used. Number (n), mean, standard deviation (SD), median, quartile range (Q1, Q3), minimum (min), and maximum (max) for continuous variables, and number and percentage for categorical variables were provided. Results: Patients (N=286, 24 initially placebo and 262 initially romiplostim) had median (Q1, Q3) age of 10 (6, 13) years, ITP duration of 1.9 (1, 4) years, and baseline platelet count of 14 (8, 23)×109/L. Previously, 88% had received corticosteroids, 87% IVIg, and 21% rituximab; 23% had received >3 prior treatments and 7% had prior splenectomy. Of the 282 patients exposed to romiplostim (20 initially received placebo), the median (min, max) duration of treatment was 65 (8, 471) weeks, with a median (min, max) average weekly dose of 6.6 (0.1, 9.7) μg/kg; total exposure was 468 patient-years. The most common reasons for discontinuing the parent study for romiplostim-treated patients were per protocol (19%; eg, sponsor decision, death, lost to follow-up), consent withdrawn (3%), noncompliance (1%), and administrative decision (1%). Of romiplostim-treated patients, 24% had serious adverse events (SAEs), most commonly epistaxis, low platelet counts, and headache (Table). There were 7 cases of postbaseline neutralizing antibody against romiplostim: 2 transient and 5 persistent. There were no neutralizing antibodies against endogenous TPO. For patients undergoing bone marrow biopsies in the 3-year open-label trial, there were no findings of collagen or bone marrow abnormalities (Year 1 n=27, Year 2 n=5, vs. baseline) (Grainger et al, ASH 2017). One patient had an increase in modified Bauermeister bone marrow grade from 0 to 2 (fine reticulin fiber network) with no associated AEs (the only AEs were a cold and injection site pain); per protocol, there was no follow-up biopsy. Once at a steady dose of 10 μg/kg, most (11/16) of this patient's platelet counts were ≥30×109/L. Investigators reported thrombocytosis AEs; 1 patient had a platelet count of 1462×109/L at Week 14 for 1 week and another had elevated platelet counts 10 times between Weeks 20-172 (max of 872×109/L); there were no associated thrombotic events. Median platelet counts rose quickly and were over 50×109/L from Week 12 on (Figure). Platelet response rates also rose quickly. Overall, 89% of romiplostim-treated patients (vs 8% of placebo) had a platelet response (platelet counts ≥50×109/L; Figure). For romiplostim-treated patients, the first platelet responses occurred after a median of 6 weeks. The median % (Q1, Q3) of months responding was 76% (25%, 93%) and # of months responding was 11 (3, 20); from time of first monthly response, the median (Q1, Q3) % of months responding was 92% (75%, 100%) and # of months responding was 14 (7, 23). Nineteen romiplostim-treated patients discontinued all ITP therapies including romiplostim for ≥6 months while maintaining platelet counts ≥50×109/L (here defined as remission). These treatment-free periods lasted a median (Q1, Q3) of 12 (8, 14) months; no placebo patients remained free of treatment. There were no clear differences between those who did and did not enter remission (ie, age, sex, race, past treatment, ITP duration, baseline platelet count). Bleeding was reported for most (68%) patients: mostly grade 1/2, with 10% having grade 3 bleeding (most commonly epistaxis in 13 patients) and 2 patients having grade 4 bleeding (both reported as "ITP"). Conclusions: In this comprehensive database of romiplostim ITP trials in 286 children with 468 patient-years of romiplostim exposure, romiplostim was well tolerated. With romiplostim, the vast majority (89%) of patients had a platelet response, with some children able to discontinue all ITP treatments for ≥6 months. Disclosures Tarantino: Health Resources and Services Administration: Research Funding; Centers for Disease Control and Prevention: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Other: Reviews grants; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Grifols: Research Funding, Speakers Bureau. Despotovic:AmGen: Research Funding; Sanofi: Consultancy; Novartis: Research Funding. Grainger:Biotest: Consultancy; Ono Pharmaceuticals: Consultancy; Amgen: Consultancy, Honoraria, Other: Educational grant; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cooper:Amgen, Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim:Amgen Inc.: Employment, Equity Ownership. Eisen:Amgen Inc.: Employment, Equity Ownership.

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Efficacy, Safety and Tolerability of E5501 (AKR501) In a 6-Month Extension Study In Subjects with Chronic Immune Thrombocytopenia (ITP).

Blood ◽

10.1182/blood.v116.21.3695.3695 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3695-3695 ◽

Cited By ~ 2

Author(s):

James B. Bussel ◽

Jenny Zhang ◽

Shande Tang ◽

Joe McIntosh ◽

David J. Kuter

Keyword(s):

Platelet Count ◽

Board Of Directors ◽

Research Funding ◽

Extension Study ◽

Dose Titration ◽

Platelet Response ◽

Open Label ◽

Advisory Committees ◽

Once Daily ◽

Grade 3

Abstract Abstract 3695 The thrombopoietin (TPO) receptor agonist E5501 (AKR501) is one of a new class of oral TPO agents which increase platelet production. In a recent multicenter, randomized, double-blind, placebo-controlled Phase II study (501-CL-003) in subjects with chronic ITP who were refractory to, or relapsed after, at least one prior ITP therapy, E5501 (once-daily for 28 days) was well tolerated and, at higher dose, was effective at increasing platelet counts. Here, 53 of 57 subjects who completed 28 days of study treatment (placebo, 2.5, 5, 10 or 20 mg E5501) in 501-CL-003 were treated with E5501 in a 6-month extension study, 501-CL-004. Subjects classified as responders in 501-CL-003 (i.e. those whose platelet count had risen by a minimum of 20 ×109/L above baseline to ≥50 ×109/L at Day 28) continued to receive their original E5501 blinded dose when they entered 501-CL-004. Subjects who were nonresponders in 501-CL-003 initially received open-label E5501 10 mg once-daily. E5501 dose was titrated upwards in an open-label fashion in 10 mg increments every 14 days depending on subject response (to a maximum of 40 mg once-daily for nonresponders and blinded dose plus 20 mg once-daily for responders). Additionally, concomitant medications were reduced according to subject response. Effectiveness analyses included only the 53 subjects in 501-CL-004. Safety analyses were performed on combined data from 501-CL-003 and 501-CL-004 (n=64). Subjects were regarded as responders in 501-CL-004 if their platelet count was ≥50 ×109/L and had risen by a minimum of 20 ×109/L above baseline (from 501-CL-003). Subjects had an overall platelet response if, in the absence of rescue medication, they were responders for 75% of the time over the last 14 weeks of the 24 week study (‘durable platelet response’) or were responders on any 4 consecutive weeks (‘transient platelet response’). E5501 showed effectiveness as measured by durable and overall platelet response. The durable platelet response rate was 52.8% for all subjects, 72% for subjects who were responders in 501-CL-003, and 35.7% for subjects who had been nonresponders. The overall platelet response rate was 75.5% for all subjects, 88% for responders, and almost two thirds (64.3%) for nonresponders. Following treatment with E5501, median platelet counts were maintained for the duration of treatment (Figure 1). E5501 also showed effectiveness as measured by a reduction or withdrawal of concomitant steroid medications. Among subjects using steroids, 54.2% decreased their use by >50%, including 33.3% who discontinued their use permanently. Twenty of 25 (80%) responders from 501-CL-003 maintained a platelet response throughout 501-CL-004 without requiring an upward dose titration. Twenty-one of 28 nonresponders required, but only 10 subjects received, an upward dose titration; of these, 7 (70%) achieved an overall response. E5501 was well tolerated, with a favorable safety profile. All 64 subjects (100%) experienced one or more treatment-emergent adverse events (TEAEs); most were mild, transient, and resolved completely. The most common TEAEs were fatigue (37.5%), headache (32.8%) and epistaxis (25%). TEAEs leading to study discontinuation were reported in 10/64 (15.6%) subjects. Serious TEAEs were reported in 12/64 (18.8%) subjects (Table 1). Of these, only 4 (6.3%) were considered by the investigators to be treatment-related. Forty-three of 64 subjects (67.2%) reported a bleeding event; 3 had a clinically significant grade 3 bleed (epistaxis, hemorrhagic diathesis or intracranial bleed) and 1 had a grade 4 GI bleed related to hemorrhagic gastritis. None were considered to be related to study drug. All other bleeding events were grades 1 or 2. Nine subjects met the criteria for recurrence of thrombocytopenia, defined as a platelet count that decreased to <10 ×109/L upon discontinuation of E5501. Four of these were deemed serious; all 4 recovered. Thromboembolic events were reported in 4 of 64 subjects (6.3%). One had a grade 3 deep vein thrombosis, 1 had a grade 3 stroke, and 1 had TIA and MI (Day 20) and a grade 4 retinal artery occlusion (14 days posttreatment). All 3 of these subjects had multiple risk factors for thrombosis. The fourth subject had grade 1 superficial thrombophlebitis. In conclusion, results from this 6-month extension study are supportive of the long-term efficacy and safety of E5501 in adults with difficult-to-manage, relapsed or refractory ITP. Disclosures: Bussel: Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; Immunomedics: Research Funding; Ligand: 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, Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sysmex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Portola: Consultancy. Zhang:Eisai: Employment. Tang:Eisai: Employment. McIntosh:Eisai: Employment. Kuter:Amgen: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; ONO: Consultancy; Shionogi: Consultancy, Research Funding; Pfizer: Consultancy; Protalix: Consultancy, Research Funding; Risk Managment Foundation: Consultancy.

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

Blood ◽

10.1182/blood.v118.21.2085.2085 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2085-2085

Author(s):

Chris L. Pashos ◽

Christopher R Flowers ◽

Mark Weiss ◽

Nicole Lamanna ◽

Charles M Farber ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Age Groups ◽

Lymphocytic Leukemia ◽

Age Group ◽

Employment Equity ◽

Advisory Committees ◽

Related Quality ◽

Health Related ◽

Equity Ownership

Abstract Abstract 2085 Introduction. Although advanced patient age is commonly used as a factor in selecting therapy for patients with chronic lymphocytic leukemia (CLL), based on presumed associations with functional status, limited data exist regarding the relationships between age and physical, emotional, social, and functional well being. We examined the relationships between age and these domains of health-related quality of life (HRQOL) for CLL patients treated in US community practices. Methods. Baseline data were collected as part of Connect CLL®, a prospective observational registry initiated in March 2010 involving centers in the US. Data on patient demographics and clinical characteristics were provided by clinicians. HRQOL was self-reported by patients in the clinic at enrollment. Patients completed 3 psychometrically validated instruments: the Brief Fatigue Inventory (BFI), EQ-5D, and Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu). Standard analyses were conducted of each instrument given clinical characteristics at that time. Reported mean BFI, EQ-5D and FACT-Leu scores were analyzed by age group (<65, 65–74, >74). Statistical significance of score differences among sub-cohorts was ascertained by ANOVA using SAS 9.1. Results. Baseline HRQOL data were reported by 604 patients, enrolled from 161 centers. Patients were predominantly male (62%) and white (90%) with mean age at 69.9 (standard deviation [SD] 11.2) yrs. HRQOL scores by age group are presented: There were no significant differences between the age groups in fatigue as measured by the BFI, or differences in overall HRQOL as measured by the EQ-5D Visual Analogue Scale (VAS) or the FACT-G. Anxiety/depression and self care are EQ-5D domains that also did not vary by age. Although mobility was most impaired in the oldest age group compared to the two younger groups, usual activities and pain/discomfort were worse in both the younger and older cohorts compared to those 65–74 years of age. FACT-Leu results indicated that the social/family domain scores did not vary by age, but that physical, emotional, and functional domains did vary statistically with the oldest typically doing better than the 65–74 year olds, but not necessarily better than those <65. Conclusions. Initial results from the Connect CLL® Registry indicate that HRQOL does not worsen monotonically with older age. In this cohort, both the youngest and oldest age groups had worse HRQOL in certain domains, presenting an inverted v-shaped relationship. Future analyses should be conducted on: (1) how HRQOL may be affected over time with changes in disease; and, (2) how HRQOL may be influenced by alternative therapies. Results reported here should serve as a useful baseline reference. Disclosures: Pashos: Celgene: Membership on an entity's Board of Directors or advisory committees. Flowers:Genentech/Roche (unpaid): Consultancy; Celgene: Consultancy; Millennium/Takeda: Research Funding; Wyeth: Research Funding; Novartis: Research Funding. Weiss:Celgene: Membership on an entity's Board of Directors or advisory committees. Lamanna:Celgene: Membership on an entity's Board of Directors or advisory committees. Farber:Celgene: Membership on an entity's Board of Directors or advisory committees. Kipps:Igenica: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Abbot Industries: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; GSK: Research Funding; Gilead Sciences: Consultancy, Research Funding; Amgen: Research Funding. Lerner:Celgene: Membership on an entity's Board of Directors or advisory committees. Kay:Celgene: Membership on an entity's Board of Directors or advisory committees. Sharman:Celgene: Membership on an entity's Board of Directors or advisory committees. Grinblatt:Celgene: Membership on an entity's Board of Directors or advisory committees. Flinn:Celgene: Membership on an entity's Board of Directors or advisory committees. Kozloff:Celgene: Membership on an entity's Board of Directors or advisory committees. Swern:Celgene Corporation: Employment, Equity Ownership. Kahn:Celgene Corporation: Employment, Equity Ownership. Street:Celgene: Employment, Equity Ownership. Sullivan:Celgene: Employment, Equity Ownership. Keating:Celgene: Membership on an entity's Board of Directors or advisory committees.

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Final Results from an International, Multi-Center, Single-Arm Study Evaluating the Safety and Efficacy of Romiplostim in Adults with Primary Immune Thrombocytopenia (ITP),

Blood ◽

10.1182/blood.v118.21.3279.3279 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3279-3279 ◽

Cited By ~ 6

Author(s):

Ann Janssens ◽

Michael D. Tarantino ◽

Robert Bird ◽

Maria Gabriella Mazzucconi ◽

Ralph Vincent V. Boccia ◽

...

Keyword(s):

Bone Marrow ◽

Platelet Count ◽

Board Of Directors ◽

Research Funding ◽

Platelet Response ◽

Employment Equity ◽

Advisory Committees ◽

Platelet Production ◽

Platelet Counts ◽

Equity Ownership

Abstract Abstract 3279 Background: ITP is an autoimmune disorder characterized by increased platelet destruction and suboptimal platelet production. Romiplostim stimulates platelet production via the TPO-receptor, and is recommended for second- and third-line treatment of chronic ITP in adults. We report final data from a large prospective study of romiplostim in adults with ITP of varying duration and severity. Methods: Eligibility criteria were broad: patients ≥18 years of age, who had received prior ITP therapies (final protocol amendment: ≥1, previous amendments: ≥3), with low platelet counts (final amendment: ≤ 30 × 109/L, previous amendments: ≤ 10, ≤ 20 × 109/L) or experiencing uncontrolled bleeding. The only excluded comorbidities were: hematological malignancy, myeloproliferative neoplasms, MDS and bone marrow stem cell disorder. Romiplostim was initiated at 1 (final amendment) or 3 (previous amendments) μg/kg/week, with dose adjustments allowed to maintain platelet counts ≥50 × 109/L. Patients could continue on study until they had access to commercially available romiplostim. Rescue medications were allowed at any time; concurrent ITP therapies could be reduced when platelet counts were > 50 × 109/L. Primary endpoint was incidence of adverse events (AEs) and antibody formation. Secondary endpoint was platelet response, defined as either (1) doubling of baseline count and ≥ 50 × 109/L or (2) ≥20 × 109/L increase from baseline. Results: A total of 407 patients received romiplostim, 60% of whom were female. Median (Q1, Q3) time since ITP diagnosis was 4.25 (1.20, 11.40) years (maximum 57.1 years), with 51% of patients splenectomised and 39% receiving baseline concurrent ITP therapies. Seventy-one percent of patients completed the study, with requirement for alternative therapy and withdrawn consent the most common reasons for discontinuation (5% each). Median (Q1, Q3) on-study treatment duration was 44.29 (20.43, 65.86) weeks (maximum 201 weeks), with a total of 20,201 subject-weeks on study. Incidence and type of AEs were consistent with previous studies. The most common serious treatment-related AEs were cerebrovascular accident, headache, bone marrow reticulin fibrosis (with no evidence of positive trichrome staining for collagen and no evidence suggesting primary idiopathic myelofibrosis), nausea, deep vein thrombosis, hemorrhage and pulmonary embolism, with each reported in 2 of 407 (0.5%) patients. All other serious treatment-related AEs were each reported in one patient. Eighteen patients died; 3 deaths (hemolysis, intestinal ischaema, aplastic anemia) were considered treatment-related. No neutralizing antibodies to romiplostim or TPO were reported. Approximately 90% of patients achieved each of the platelet response definitions, regardless of splenectomy status. Overall, median (Q1, Q3) time to response was 2 (1, 4) weeks for response definition 1, and 1 (1, 3) week for response definition 2. Median (Q1, Q3) baseline platelet count was 14 (8, 21) × 109/L. After 1 week of treatment median (Q1, Q3) platelet count had increased to 42 (18, 101) × 109/L. From week 8 onwards, and excluding counts within 8 weeks of rescue medication use, median platelet counts were consistently above 100 × 109/L (range 101.0–269.5 × 109/L). Median (Q1, Q3) average weekly romiplostim dose was 3.62 (1.99, 6.08) μg/kg. Summary/conclusions: This is the largest prospective study in adult ITP reported to date. The data reported here are similar to those reported for previous romiplostim studies, with romiplostim able to safely induce a rapid platelet response in adult ITP patients with low platelet counts or bleeding symptoms. Romiplostim is an important, well-tolerated, treatment option for adult ITP patients, which significantly increases and maintains platelet counts. Adverse Event Subject Incidence Platelet Response Disclosures: Janssens: Amgen: Consultancy; Roche: Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees. Tarantino:Cangene corporation: Research Funding; Baxter: Research Funding; Talecris: Honoraria, Speakers Bureau; Up-to-date: Patents & Royalties; The Bleeding and Clotting Disorders Institute: Board Member. Bird:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees. Boccia:Amgen: Equity Ownership, Honoraria, Speakers Bureau. Lopez-Fernandez:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kozak:Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Steurer:Amgen: Honoraria. Dillingham:Amgen Limited: Employment, Equity Ownership. Lizambri:Amgen: Employment, Equity Ownership.

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Health-Related Quality of Life in a Biologic Assignment Trial of Reduced Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome

Blood ◽

10.1182/blood-2021-147514 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 421-421

Author(s):

Rachel Cusatis ◽

Michael Martens ◽

Ryotaro Nakamura ◽

Corey Cutler ◽

Wael Saber ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Health Related Quality ◽

Advisory Committees ◽

No Donor ◽

Free Survival ◽

Related Quality ◽

Health Related

Abstract Introduction The Blood and Marrow Transplant Clinical Trials Network study (BMT CTN 1102, NCT02016781) was a multicenter, biologic assignment trial in older adults aged 50-75 with higher risk de novo MDS (IPSS Intermediate-2 or High) who were candidates for reduced-intensity conditioning (RIC) allogeneic HCT. The trial compared outcomes of those with a suitable HLA-identical sibling or unrelated donor (Donor arm) to those where no donor was identified (No Donor arm) within a search window of 90 days. The trial reported a survival benefit for patients in the Donor arm compared to the No Donor arm [Nakamura et al, JCO 2021, in press]. Here, we compare the health-related quality of life (QOL) for patients between the two arms through 36 months after enrollment. We also describe the predictors and trajectories of QOL. Methods English and Spanish-speaking subjects were invited to complete patient-reported outcome (PRO) measures, including the Functional Assessment of Cancer Therapy - General (FACT-G), the SF-36 yielding a Physical Component Score (PCS) and Mental Component Score (MCS), and the EQ-5D, at enrollment and every 6 months until 24 months, then 36 months after enrollment. Validation studies indicate a clinically meaningful difference of 5 points for FACT-G, PCS, and MCS and 2 points for associated subscales. To account for the missingness of assessments, including those missing due to death, we compared each score between arms using an inverse probability weighted - independent estimating equation (IPW-IEE) model, which models the scores in surviving patients while using IPW to account for baseline variables and follow-up outcomes that impact the likelihood of missingness. Since 4 scores were evaluated, a Bonferroni corrected significance level of 1.25% = 5% / 4 was used. Cox regression models were used to evaluate the impact of QOL measures on overall and leukemia free survival. The IPW-IEE models adjust for baseline score and follow-up assessment time as well as age, race/ethnicity, performance status, IPSS score, duration of disease, and response to prior hypomethylating therapy; the Cox models adjusted for the 6 latter variables and treatment arm. Trajectories of QOL are shown by plotting mean +/- standard error by group over time. Results Between January 2014 and November 2018, 384 subjects (median age 66.7 years, range: 50.1-75.3) were enrolled at 34 centers and biologically assigned to Donor (n=261) or No Donor arm (n=123) by 90 days from enrollment. For the Donor arm the median duration from registration to HCT was 3.9 months (range 0.3-20.7). Completion rates were generally high at 65-78% of eligible survivors at each timepoint. At enrollment, 204 subjects (78.2%) in the Donor arm and 85 subjects (69.1%) in the No Donor arm completed at least one QOL form, with 4 patients unable to complete due to language (non-English or Spanish speaking). While there were some small differences at 18 months favoring the Donor arm, no clinically significant differences in PRO scores or subscales were seen between the arms at any timepoint (Figure 1) or in the scores over time. In general, similar trajectories for the Donor arm were seen for each PRO, with most decreasing or stable from baseline to 6 months and improving thereafter. Compared to published averages of U.S cancer populations, FACT-G means in both arms were higher beginning at 18 months. Baseline and 6-month PRO scores were the strongest predictors of later PRO scores despite adjusting for patient demographic and clinical factors. Overall survival was predicted by baseline FACT-G <70 (HR=1.61, p<.01) and PCS scores <40 (HR=1.82, p<0.001), while leukemia-free survival was predicted by baseline FACT-G <70 (HR=1.61, p<0.01) and PCS <40 (HR=1.80, p<0.002). No associations of PROs with AML transformation, relapse, or acute or chronic GVHD were found. Non-compliance with biologic assignment was less likely in Donor arm compared to No Donor, but baseline QOL was not a confounding factor. Conclusion In older adults with MDS, the survival advantage associated with Donor availability and HCT does not come at the cost of worse QOL in comparison to the No Donor arm. Baseline PRO scores were the strongest independent predictors of subsequent QOL outcomes and survival, even after controlling for clinical and patient-level factors. These results should reassure older patients and clinicians who prefer curative approaches to MDS. Figure 1 Figure 1. Disclosures Cutler: Mallinckrodt: Consultancy; Editas: Consultancy; CareDx: Consultancy; Kadmon: Consultancy; Pfizer: Consultancy; Incyte: Consultancy; Cimeio: Consultancy; Deciphera: Consultancy; Omeros: Consultancy; Syndax: Consultancy; Mesoblast: Consultancy; Jazz: Consultancy. Saber: Govt. COI: Other. Lee: Takeda: Research Funding; Syndax: Research Funding; Pfizer: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kadmon: Research Funding; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Janssen: Other; Incyte: Research Funding; AstraZeneca: Research Funding; Amgen: Research Funding. Shaw: mallinkrodt: Other: payments; Orca bio: Consultancy. Horowitz: Magenta: Consultancy, Research Funding; Astellas: Research Funding; Jazz Pharmaceuticals: Research Funding; GlaxoSmithKline: Research Funding; Genentech: Research Funding; CSL Behring: Research Funding; Gamida Cell: Research Funding; Allovir: Consultancy; Daiicho Sankyo: Research Funding; Amgen: Research Funding; bluebird bio: Research Funding; Chimerix: Research Funding; Actinium: Research Funding; Medac: Research Funding; Kiadis: Research Funding; Xenikos: Research Funding; Vor Biopharma: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Pharmacyclics: Research Funding; Pfizer, Inc: Research Funding; Orca Biosystems: Research Funding; Omeros: Research Funding; Novartis: Research Funding; Miltenyi Biotech: Research Funding; Mesoblast: Research Funding; Kite/Gilead: Research Funding; Janssen: Research Funding; Sanofi: Research Funding; Seattle Genetics: Research Funding; Shire: Research Funding; Sobi: Research Funding; Stemcyte: Research Funding; Takeda: Research Funding; Tscan: Research Funding; Vertex: Research Funding.

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Safety and Efficacy of Combined Ruxolitinib and Thalidomide in Patients with Myelofibrosis: Initial Results of a Phase II Study

Blood ◽

10.1182/blood-2018-99-114125 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 354-354 ◽

Cited By ~ 7

Author(s):

Raajit K. Rampal ◽

Srdan Verstovsek ◽

Sean M Devlin ◽

Eytan M. Stein ◽

Tapan M. Kadia ◽

...

Keyword(s):

Platelet Count ◽

Combination Therapy ◽

Board Of Directors ◽

Phase Ii ◽

Research Funding ◽

Single Agent ◽

Response Assessment ◽

Platelet Response ◽

Advisory Committees ◽

Grade 3

Abstract Background: Among the most frequent and challenging hematologic manifestations of myelofibrosis (MF) are anemia and thrombocytopenia, the presence of which portends an adverse outcome. Few effective modalities to address these cytopenias exist, particularly thrombocytopenia. Further, although the FDA-approved JAK1/2 inhibitor Ruxolitinib (RUX) has demonstrated significant clinical efficacy in MF patients, RUX frequently results in anemia and thrombocytopenia. Thrombocytopenia in particular often results in dose attenuation of RUX. Thalidomide (THAL) is a first-in-class immunomodulatory agent. Studies of THAL in MF patients, alone and with prednisone, have demonstrated improvements in anemia and thrombocytopenia. We therefore sought to examine whether combination of RUX and THAL could result in improvement in both disease-related and therapy-related cytopenias, as well as improve overall disease response in patients with MF. Here we report initial analysis of this study (NCT03069326). Methods: We conducted a multicenter two stage phase II trial designed to assess the effect of RUX and THAL combination in subjects with primary, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis. Patients taking RUX at the time of enrollment must have had less than PR per IWG-MRT/ELN 2013 criteria, or be refractory, to RUX single-agent therapy. Patients must have been taking RUX for a minimum of 3 months, and must have been on a stable dose of RUX for a minimum of 4 weeks immediately prior to enrollment. Treatment-naïve patients received single-agent RUX for 3 months (run-in phase) per label, and went on to combination therapy if they achieved less then a PR per IWG-MRT/ELN criteria. Each cycle of therapy was 28 days. Response assessment was evaluated according to the IWG-MRT/ELN 2013 criteria. Platelet response criteria in patients with baseline thrombocytopenia (less than lower limit of normal) included: Major response (≥75% increase in platelet count), Intermediate Response (≥50% increase) and Minor Response (≥25% increase). Adverse events were assessed using the NCI CTCAE v. 4.0. The primary endpoint was the proportion of treated subjects that achieved a response by IWG-MRT criteria and by platelet response criteria. Results: A total of 25 patients are planned to be accrued. At the time of this writing, a total of 18 patients have been accrued. The median age was 70.5 years (47-85). 8 patients had received prior therapies other than RUX, including imetelstat, momelotinib, danazol, pomalidomide, darbepoetin alpha and sotatercept. 7 patients enrolled to the run-in phase. 14 patients received red blood cell transfusions prior to study enrollment. Evaluation of platelet count in patients with baseline thrombocytopenia demonstrated a significant increase in platelet count at cycle 3 of therapy compared to baseline (Figure 1A and B; P<0.05). An increase in Hgb was observed over successive cycles of combination therapy (Figure 1C and D). 5 of 18 accrued patients completed ≥6 cycles of combined therapy at the time of abstract submission and were thus evaluable for response assessment. The overall response rate in these patients was 80% (4/5 patients). Clinical Improvement (Anemia response and Symptom response) occurred in 3 patients (both responses observed in all 3 patients). Major platelet response was observed in 4 of 5 patients with baseline thrombocytopenia. 1 patient met criteria for spleen response (Table 1). Grade 3/4 non-hematologic adverse events regardless of attribution included; limb edema, diverticulitis, hypertension, syncope. 1 patient experienced a thromboembolic event. 1 patient experienced a grade 3 hematologic AE (neutropenia). Conclusions: The combination of THAL and RUX has demonstrated a promising efficacy signal in this initial analysis of an ongoing phase II study, and appears to be well tolerated. Platelet count increases were observed in all patients who entered study with baseline thrombocytopenia, a response which appears to be maintained in the majority of patients observed 6 months after starting combination therapy. As well, anemia responses were observed in 3 of 5 evaluable patients. Collectively, these data indicate a potential role for this regimen in patients with anemia and/or thrombocytopenia, who otherwise have limited treatment options. Updated data on duration of response and overall response of all accrued patients will be presented. Disclosures Rampal: Constellation: Research Funding; Celgene: Honoraria; Incyte: Honoraria, Research Funding; Jazz: Consultancy, Honoraria; Stemline: Research Funding. Verstovsek:Italfarmaco: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Stein:Celgene: Consultancy; Bayer: Consultancy; Agios: Consultancy; Daiichi Sankyo: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Kadia:Pfizer: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy; Amgen: Consultancy, Research Funding; Takeda: Consultancy; Takeda: Consultancy; Celgene: Research Funding; BMS: Research Funding; Novartis: Consultancy; Abbvie: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Research Funding; BMS: Research Funding; Jazz: Consultancy, Research Funding; Abbvie: Consultancy; Jazz: Consultancy, Research Funding. Mauro:Bristol-Myers Squibb: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Takeda: Consultancy. Pemmaraju:SagerStrong Foundation: Research Funding; daiichi sankyo: Research Funding; novartis: Research Funding; abbvie: Research Funding; cellectis: Research Funding; samus: Research Funding; Affymetrix: Research Funding; stemline: Consultancy, Honoraria, Research Funding; celgene: Consultancy, Honoraria; plexxikon: Research Funding. Bose:Blueprint Medicines Corporation: Research Funding; Astellas Pharmaceuticals: Research Funding; Incyte Corporation: Honoraria, Research Funding; Constellation Pharmaceuticals: Research Funding; Celgene Corporation: Honoraria, Research Funding; Pfizer, Inc.: Research Funding; CTI BioPharma: Research Funding.

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Longitudinal Changes of Impairments in Health-Related Quality of Life in Lower-Risk MDS Patients: A European Leukemianet Study

Blood ◽

10.1182/blood-2018-99-112508 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3097-3097

Author(s):

Reinhard Stauder ◽

Ge Yu ◽

Karin A Koinig ◽

Dominic Culligan ◽

Pierre Fenaux ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Self Care ◽

Initial Diagnosis ◽

Health Related Quality ◽

Advisory Committees ◽

Related Quality ◽

Health Related ◽

Anxiety Depression

Abstract Introduction Patient perception and perspective have become relevant in individualised therapy planning in MDS. Thus, integration of patient-reported outcomes (PRO), including health-related quality of life (HRQoL), in studies and in clinical practice is essential. We demonstrated recently pronounced impairments in HRQoL in patients with MDS (Stauder et al., Leukemia 2018). However, longitudinal data on aspects of HRQoL in MDS are rare. Objectives 1. To describe longitudinal changes of HRQoL in MDS and 2. To compare the time course in different patient subgroups to define patients at high risk of deterioration of HRQoL. Methods The EUMDS Registry is a prospective, non-interventional longitudinal study, enrolling newly diagnosed patients with IPSS low or intermediate-1 MDS from 143 haematology centres in 17 European countries and Israel. HRQOL was assessed by EQ-5D questionnaire. Patients were selected, if they fully completed the EQ-5D score (five dimensions and VAS) at baseline and at 6 and 12 months, resulting in a total of 743 subjects at 86 centres in 15 countries. Differences in response for the five EQ-5D dimensions between patients subgroups were evaluated using chi-squareMcNemar tests. For EQ-VAS, the mean score with standard deviation was calculated. Wilcoxon's signed ranks tests were conducted to identify changes over time between HRQOL values at baseline and at 6, 12 months. Results Moderate/severe impairments at initial diagnosis were observed in the dimensions mobility (39.4%), self-care (10.2%), usual activities (32.6%), pain discomfort (46.6%) and anxiety/depression (36.7%). As compared with baseline a pronounced increase in moderate/severe problems was observed at 12 months in the dimensions self-care (10.2% (baseline) vs 15.5% (12 mo); p=0.003) and in usual activities (32.6% vs 40.6%; p=0.001). In contrast, self-reported mobility, pain and anxiety/depression did not change significantly. Decrease in VAS over time revealed a trend toward significance (75 vs. 70; p=0.056). More pronounced impairment of HRQOL was most significantly observed in patients of advanced age: 60-75 yrs in self-care 8.3% vs 14.3% (p=0.016) and in usual activities 28% vs 35.7% (p=0.032); in persons 75+ years in self-care 14.2% vs 19.8% (p=0.058) and in usual activities 48.7% vs 50.3% (p=0.003). Similarly, VAS significantly decreased in the latter group from 70 to 66 (p=0.038). Increases in impairments were most prominent in male patients in self-care (9.7 vs 16.7%; p=0.002) and in usual activities (29.4 vs 38.7%; p=0.003), whereas in women HRQoL at the different time points was not significantly different. Pronounced decreases in HRQoL aspects was observed in anemic patients (Hb-levels <10g/dl) at initial diagnosis: mobility 47.4 vs 55.2% (p=0.06), self-care 13.5 vs 21.1% (p=0.015), usual activities 41.3 vs 52.7% (p=0.006), pain/discomfort 43.3 vs 55.6% (p=0.058) and VAS (70 vs 68; p=0.051). A reduction in HRQoL was observed even in patients with a Hb-level ≥10 g/dl in the dimension self-care (7.9 vs 12.1%; p=0.042). Pronounced decreases in problems in HRQoL were observed in anemic patients (Hb<10 g/dL) who received transfusions in self-care (18.1% vs 25.6%; p=0.029), in usual activities (43.6% vs 61.5%; p=0.038), and in VAS (67.3 vs 61.9; p=0.003). Transfusion dependent patients were at high risk to develop impairments in VAS (70 vs 64; p=0.006) and in most dimensions of EQ-5D (mobility 50.2 vs 62%, p=0.017), self-care (8.8 vs 11.5%, p=0.017), usual activities (41.6 vs 62.9%, p=0.01) and pain/discomfort (48.3 vs 58.5%, p=0.038). Conclusions Low-risk MDS patients report relevant restrictions in distinct dimensions at initial diagnosis. A relevant drop in HRQoL is observed at 12 months particularly in self-care and in usual activities. Patients of advanced age, males and those with initial low Hb-levels most frequently reported declines in HRQoL. Transfusion-need represents a relevant predictor of deterioration of HRQoL. These analyses form the basis to identify vulnerable patients and to tailor individualized interventions and treatment approaches. Analyses are planned to unravel the role of intervention therapies on observed changes in HRQoL. Disclosures Stauder: Teva: Research Funding; 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. Fenaux:Celgene: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Roche: Honoraria; Otsuka: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Garelius:novartis: Honoraria. Efficace:Incyte: Consultancy; Amgen: Consultancy; TEVA: Consultancy; Bristol Meyers Squibb: Consultancy; Orsenix: Consultancy; Seattle Genetics: Consultancy; Lundbeck: Research Funding; TEVA: Research Funding; AMGEN: Research Funding. de Witte:Amgen: Consultancy, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Research Funding.

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An Interim Analysis Of a Phase 2, Single-Arm Study Of Platelet Responses and Remission Rates In Patients With Immune Thrombocytopenia (ITP) Receiving Romiplostim

Blood ◽

10.1182/blood.v122.21.1074.1074 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1074-1074 ◽

Cited By ~ 1

Author(s):

Roberto Stasi ◽

Adrian Newland ◽

Bertrand Godeau ◽

Victor Priego ◽

Jean-Francois Viallard ◽

...

Keyword(s):

Platelet Count ◽

Adverse Events ◽

Board Of Directors ◽

Treatment Period ◽

Research Funding ◽

Alternative Therapy ◽

Platelet Response ◽

Advisory Committees ◽

Serious Adverse Events ◽

Platelet Counts

Abstract Background We describe here platelet response and remission observed with romiplostim treatment in patients with ITP. Methods Patients with an ITP diagnosis for less than 6 months who received first-line therapies only (ie, corticosteroids, IVIG, anti-D) received QW romiplostim for up to 12 months in the treatment period (Fig 1). The primary objective was to describe the number of months with a platelet response during the 12-month treatment period; secondary objectives included incidence of ITP remission and splenectomy. The romiplostim dose was increased QW by 1 μg/kg from 1 μg/kg up to 10 μg/kg to reach a platelet count of ≥50x109/L, adjusting to maintain a platelet count of 50-200x109/L. Patients who maintained platelet counts ≥50x109/L on romiplostim only entered a dose-tapering period in which the romiplostim dose was decreased by 1 μg/kg Q2W as long as platelet counts remained ≥50x109/L. Starting when the dose tapered to 0 during either the 12-month treatment period or at the end of the dose-tapering period, patients were followed to determine whether they had ITP remission (24 weeks platelet counts ≥50x109/L without any treatment for ITP, including romiplostim). At the end of 12 months, patients who 1) had platelet counts ≤20x109/L for <4 consecutive weeks, 2) had platelet counts of 20-50x109/L, and/or 3) were receiving treatment for ITP besides romiplostim had the option to enter a stabilization period (≤8 weeks) while the investigator determined suitable post-study therapy. Patients with platelet counts ≤20x109/L for ≥4 consecutive weeks on the highest romiplostim dose were discontinued from the study for non-response. Interim data up to March 2013 are reported here. Results Of the patient population (N = 71), 59.2% were women, median (Q1, Q3) age was 37 (28, 56) years, median (Q1, Q3) time since ITP diagnosis was 2.2 (0.9, 4.4) months, and median (Q1, Q3) platelet count at screening was 20 (12, 25) x109/L. Past treatments included steroids (96%), IVIG (42%), and anti-D (1%). Prior to the study, platelet transfusions were received by 9% of patients. 30 patients (42%) completed treatment, 31 (44%) are continuing treatment, and 10 (14%) discontinued romiplostim (due to consent withdrawn n = 2, adverse event n = 3, requirement for alternative therapy n = 3, lost to follow-up n = 1, death n = 1). Patients had a median (Q1, Q3) of 51 (34, 52) weeks of treatment with a median (Q1, Q3) average QW dose of 2.1 (1, 3.8) μg/kg. 66 (93%) patients had a peak platelet count ≥50x109/L. The median (Q1, Q3) time with a platelet response was 9 (6, 12) months; the median (95% CI) time to platelet response was 2.1 (1.1, 3.1) weeks; platelet counts are in Fig 2. Of 38 evaluable patients (ie, known remission status), 11 (29%, 95% CI 15% to 46%) had ITP remission. One patient had a splenectomy and 6 had treatment failure (defined as platelet count ≤20x109/L for 4 consecutive weeks at 10 μg/kg QW, requirement of alternative therapy, or death). Of the 71 patients receiving romiplostim, 9 patients had serious adverse events (2 treatment-related: 1 case each of gastritis and increased transaminases). There were also 3 adverse events leading to discontinuation of romiplostim (non-Hodgkin's lymphoma, leukocytosis, and the aforementioned increased transaminases, these last 2 treatment-related). Other serious adverse events, also occurring in 1 patient each, included atrial fibrillation, dapsone syndrome, fecaloma, the aforementioned non-Hodgkin's lymphoma, pleuritic pain, and tendon rupture. There were no fatalities reported as adverse events; the death leading to discontinuation was due to cerebral hemorrhage which began before the patient received romiplostim. The most common adverse events were headache (17%), arthralgia (13%), and nasopharyngitis (10%). The most common hemorrhage adverse events were hematoma (7%), petechiae (7%), and epistaxis (7%). No bone marrow findings were reported. Conclusions In this trial, patients with an ITP diagnosis for less than 6 months treated with romiplostim had a high response rate (over 90%), with platelet responses occurring quickly (median time to response of 2 weeks) and median number of months with a platelet response of 9 months. To date, 29% of evaluable patients have shown remission (24 weeks of platelet counts ≥50x109/L without any ITP treatment). There were no new safety signals. Updated data from this ongoing study will be presented in the future. Disclosures: Stasi: Amgen: Honoraria, Speakers Bureau; GSK: Honoraria, Speakers Bureau; Genzyme: Honoraria, Speakers Bureau; Suppremol: Consultancy. Newland:Geron: Consultancy; Amgen: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Octapharma: Research Funding. Godeau:Amgen: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Roche: Consultancy, Research Funding; GSK: Consultancy; LFB: Consultancy. Jia:Amgen: Employment, Equity Ownership. Lopez:Amgen: Employment, Equity Ownership.

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

Blood ◽

10.1182/blood.v128.22.3309.3309 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3309-3309 ◽

Cited By ~ 7

Author(s):

Heinz Ludwig ◽

Philippe Moreau ◽

Meletios A Dimopoulos ◽

Maria-Victoria Mateos ◽

Martin F Kaiser ◽

...

Keyword(s):

Quality Of Life ◽

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Sensitivity Analyses ◽

Life Questionnaire ◽

Advisory Committees ◽

Related Quality ◽

Health Related

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

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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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