Improved Quality of Life (QOL) with Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Compared with Standard of Care (SOC) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma  (LBCL): Results from the Phase 3 Transform Study

Abstract Background: Pts with previously treated R/R aggressive LBCL have compromised health-related QOL (HRQOL). Liso-cel is an autologous, CD19-directed, defined composition, 4-1BB CAR T cell product administered at equal target doses of CD8 + and CD4 + CAR + T cells. In a prespecified interim analysis of TRANSFORM (NCT03575351), a randomized, open-label, pivotal trial, liso-cel demonstrated statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival and key secondary endpoints (complete response rate and progression-free survival) in adults with R/R LBCL after failure of first-line (1L) immunochemotherapy compared with SOC, with no new safety signals. Here we present results of the pt-reported outcomes (PRO) analysis from TRANSFORM. Methods: Adults (age ≤ 75 yrs) with R/R LBCL (≤ 12 mo after 1L therapy), who were eligible for autologous stem cell transplantation (ASCT), were randomized to receive either SOC (3 cycles of salvage chemotherapy [CT] and BEAM + ASCT for responding pts) or liso-cel after lymphodepletion. Crossover to receive liso-cel was allowed in the SOC arm for pts who failed treatment. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - 30 items (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS) were administered at randomization (baseline) and on Days 29 (infusion of liso-cel or 2 cycles of salvage CT), 64 (1 mo post liso-cel or completion of CT), 126 (3 mos post liso-cel or 2 mos post ASCT), and Mo 6 and other prespecified timepoints up to Mo 36 or end of study. No PRO data were collected after crossover. The analysis was based on the PRO-evaluable population (pts with a baseline and ≥ 1 post-baseline assessment). Predefined thresholds determined clinically meaningful changes. Global health/QOL (GH/QOL), physical functioning, cognitive functioning, fatigue, pain, and FACT-LymS were the primary domains of interest based on their relevance to the study population and treatment. A linear mixed model for repeated measures (MMRM) analysis was performed to assess the between-treatment difference in overall least squares (LS) mean change from baseline for each primary domain, using data collected up to Day 126 for visits with a sample size per arm ≥ 10. Proportions of pts with meaningful change from baseline were assessed for each primary domain up to Mo 6. All analyses were descriptive only. Results: Of 184 randomized pts, 90 (49%) and 85 (46%), respectively, were included in the PRO-evaluable population for the EORTC QLQ-C30 (SOC vs liso-cel n=43 vs 47) and FACT-LymS (n=40 vs 45, respectively). The PRO assessment completion rate from baseline up to Mo 6 was ≥ 45%, which was lower than expected primarily due to operational challenges during the COVID-19 pandemic but was comparable for both arms. In the MMRM analysis, the liso-cel arm had more favorable overall LS mean changes from baseline to Day 126 than the SOC arm in most of the EORTC QLQ-C30 domains and FACT-LymS. In particular, the between-treatment differences for cognitive functioning (−2.09 vs 2.21) and fatigue (3.75 vs −1.95) for SOC versus liso-cel, respectively, exceeded the prespecified minimal important difference threshold (Table); in those domains, the SOC arm deteriorated while the liso-cel arm improved. In individual-level analyses, the proportion of pts with meaningful improvement for fatigue and GH/QOL was higher, while deterioration was lower, in the liso-cel arm versus SOC arm from baseline up to Mo 6 (Figure). At Mo 6, a higher proportion of pts experienced worsened fatigue (71% vs 18%) and a lower proportion experienced improved fatigue (29% vs 47%) in the SOC arm compared with the liso-cel arm; for GH/QOL, a higher proportion of pts worsened (57% vs 18%) and lower proportion improved (14% vs 53%), respectively. For the other primary domains, the proportions of pts with improvement or deterioration favored liso-cel or were similar between arms. Conclusions: Compared with SOC, liso-cel showed favorable improvement in most primary PRO domains, particularly EORTC QLQ-C30 cognitive functioning and fatigue and more pts showed PRO improvements and fewer showed deterioration by Mo 6 with liso-cel. The results were achieved despite only responders remaining in the SOC arm after salvage CT. HRQOL was either improved or maintained after liso-cel treatment in pts with R/R LBCL after failure of 1L therapy. Figure 1 Figure 1. Disclosures Abramson: Bristol-Myers Squibb Company: Consultancy, Research Funding; Morphosys: Consultancy; C4 Therapeutics: Consultancy; Kite Pharma: Consultancy; Kymera: Consultancy; Incyte Corporation: Consultancy; Bluebird Bio: Consultancy; Astra-Zeneca: Consultancy; Allogene Therapeutics: Consultancy; Novartis: Consultancy; EMD Serono: Consultancy; Genmab: Consultancy; Seagen Inc.: Research Funding; AbbVie: Consultancy; Karyopharm: Consultancy; Genentech: Consultancy; BeiGene: Consultancy. Arnason: Juno/BMS: Honoraria. Glass: BMS: Consultancy; Roche: Consultancy, Research Funding, Speakers Bureau; Riemser: Research Funding; Kite: Consultancy; Novartis: Consultancy; Helios Klinik Berlin-Buch: Current Employment. Crotta: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Montheard: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Previtali: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Liu: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Braverman: BMS: Current Employment, Current equity holder in publicly-traded company. Guo: Daiichi Sankyo: Consultancy; UCB: Consultancy; Janssen: Consultancy; Gilead: Consultancy; Bristol Myers Squibb: Consultancy; EMD Serono: Consultancy; Evidera: Current Employment. Shi: Bristol Myers Squibb: Consultancy. Kamdar: ADC Therapeutics: Consultancy; Adaptive Biotechnologies: Consultancy; TG Therapeutics: Research Funding; Genentech: Research Funding; AbbVie: Consultancy; KaryoPharm: Consultancy; Kite: Consultancy; AstraZeneca: Consultancy; SeaGen: Speakers Bureau; Celgene: Other; Genetech: Other; Celgene (BMS): Consultancy.

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Secondary Quality-of-Life Domains in Patients with Relapsed and Refractory Multiple Myeloma Treated with the Bcma-Directed CAR T Cell Therapy Idecabtagene Vicleucel (ide-cel; bb2121): Results from the Karmma Clinical Trial

Blood ◽

10.1182/blood-2020-136665 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 28-29

Author(s):

Nina Shah ◽

Michel Delforge ◽

Jesús F. San-Miguel ◽

Kaitlyn B. Bertin ◽

Muna J Tahir ◽

...

Keyword(s):

Quality Of Life ◽

Research Funding ◽

Statistical Significance ◽

Publicly Traded ◽

Meaningful Improvement ◽

Car T ◽

Eortc Qlq ◽

Eq Vas

Introduction: Patients with relapsed and refractory multiple myeloma (RRMM) have limited treatment options and experience poor health-related quality of life (HRQoL). Ide-cel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy, has shown a favorable clinical benefit-risk profile in patients with RRMM in the phase 2, single-arm KarMMa trial (Munshi NC, et al. J Clin Oncol 2020;38:8503). The impact of ide-cel treatment on primary HRQoL domains of interest preselected as most relevant for the treatment and target population (Fatigue, Pain, Cognitive Functioning, Physical Functioning, and Global Health) has been recently described (Delforge M, et al. HemaSphere 2020;4:EP1000). The aim of this analysis was to report the impact of ide-cel treatment on secondary HRQoL domains of interest and health utility scores in patients with RRMM in the KarMMa trial. Methods: Patients enrolled in the KarMMa trial (NCT03361748) had ≥ 3 prior antimyeloma treatment regimens (including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody) and were refractory to their last regimen per International Myeloma Working Group criteria. After lymphodepletion, patients received ide-cel at target dose levels of 150, 300 and 450 × 106 CAR+ T cells. HRQoL was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 (QLQ-C30) and Myeloma Module (MY20) questionnaires and the EuroQol 5 dimensions 5 levels (EQ-5D-5L) instrument at screening, baseline, on the day of ide-cel infusion, and throughout the follow-up period at Months 1-6, 9, 12, and 15 post-infusion. For each domain, clinically meaningful changes from baseline were predefined as recommended in the literature. Analyses were performed after the cutoff date, October 16, 2019, and included patients with ≥ 9+1 months of follow-up. Statistical significance was calculated using the 2-sided Wilcoxon signed-rank test (0.05 significance level). EQ-5D-5L utility indices were calculated using the UK value set as the reference country and compared with UK general population data. Results: Of 128/140 patients enrolled in the KarMMa trial who received ide-cel, 95% (EORTC QLQ-C30) and 94% (EORTC QLQ-MY20, EQ-5D-5L) had a baseline and ≥ 1 post-baseline HRQoL assessment and were evaluable for HRQoL. The compliance rate was ≥ 80% for most visits. For EORTC QLQ-C30, patients demonstrated a clinically meaningful improvement in most functioning and symptom subscale scores from baseline to Month 3 through 15, with statistical significance (p < 0.05) reached at various time points for different subscales throughout the follow-up period. For the Role Functioning, Emotional Functioning and Social Functioning subscales, > 40% of patients reported a clinically meaningful improvement from baseline, ~25% had deterioration and ~35% had no change from baseline from Month 2 onward (Figure shows Month 9 results). Stable status was most frequently observed (~60%) on the Nausea/Vomiting, Constipation, Diarrhea, Insomnia, Dyspnea and Appetite Loss, and Financial Difficulties subscales. For EORTC QLQ-MY20, the mean change from baseline on the Future Perspectives subscale demonstrated a clinically meaningful improvement from baseline at Month 2 through 15, with statistical significance (p < 0.05) reached at Month 5. Body Image subscale scores remained stable from baseline through Month 15. The greatest proportion of patients (> 48%) experienced a clinically meaningful improvement from baseline on the Future Perspective subscale. Stable status was most frequently observed (> 59%) for the Body Image subscale. Both EQ-5D-5L index (0.68 vs 0.86) and EQ visual analogue scale (EQ VAS) scores (68 vs 83) were lower for patients treated with ide-cel when compared with UK general population scores. The index and EQ-VAS mean scores became more comparable to the UK data over time, showing a clinically meaningful (although not statistically significant) improvement from baseline beginning at Month 2 (EQ-5D-5L) or 3 (EQ-VAS) through Month 15. In most patients, a clinically meaningful improvement from baseline was observed, increasing from ~43% to ~47% (EQ-5D-5L index score) and ~57% to ~68% (EQ-VAS). Conclusion: These results show that ide-cel treatment brings clinically meaningful quality-of-life benefits to triple-class-exposed patients with RRMM without compromising any HRQoL domains. Disclosures Shah: BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy. Delforge:Amgen: Honoraria; BMS: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria. San-Miguel:Amgen, BMS, Celgene, Janssen, MSD, Novartis, Takeda, Sanofi, Roche, Abbvie, GlaxoSmithKline and Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bertin:ICON plc: Current Employment. Tahir:ICON plc: Current Employment. Lewis:ICON plc: Current Employment. Wang:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Braverman:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Campbell:BMS: Current Employment, Current equity holder in publicly-traded company. Dhanda:BMS: Current Employment, Current equity holder in publicly-traded company. Munshi:Takeda: Consultancy; C4: Current equity holder in private company; Janssen: Consultancy; Adaptive: Consultancy; Legend: Consultancy; Amgen: Consultancy; AbbVie: Consultancy; Karyopharm: Consultancy; OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Consultancy.

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Effect of lisocabtagene maraleucel on HRQoL and symptom severity in relapsed/refractory large B-cell lymphoma

Blood Advances ◽

10.1182/bloodadvances.2020003503 ◽

2021 ◽

Vol 5 (8) ◽

pp. 2245-2255

Author(s):

Donald L. Patrick ◽

Annette Powers ◽

Monika Parisi Jun ◽

Yeonhee Kim ◽

Jacob Garcia ◽

...

Keyword(s):

Quality Of Life ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Meaningful Improvement ◽

Large B Cell Lymphoma ◽

Car T ◽

Eortc Qlq C30 ◽

Eortc Qlq ◽

Large B Cell

Abstract CD19-directed chimeric antigen receptor (CAR) T-cell therapy has shown efficacy as a third-line or later treatment in patients with relapsed/refractory large B-cell lymphoma (LBCL). Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire, we evaluated the impact of CAR T-cell treatment with lisocabtagene maraleucel (liso-cel) on health-related quality of life (HRQoL) and symptoms in patients with relapsed/refractory LBCL in the ongoing, open-label, nonrandomized TRANSCEND NHL 001 trial. Clinically meaningful improvement was observed in EORTC QLQ-C30 scores for global health status/QoL, based on a minimally important difference of 10 points at 2 to 18 months after liso-cel infusion. There were no clinically meaningful changes in physical functioning and pain, whereas clinically meaningful improvements were observed in fatigue at 2, 12, and 18 months. The proportion of patients with clinically meaningful improvement in global health status/QoL was generally higher for treatment responders than for nonresponders. A trend toward decreased mean EQ-5D-5L index scores was observed at 1 month after liso-cel infusion, followed by subsequent increases through 18 months. Mean EQ-5D-5L visual analog scale scores increased from 2 through 18 months. In summary, patients with relapsed/refractory LBCL treated with liso-cel had early, sustained, and clinically meaningful improvements in HRQoL and symptoms that correlated with antitumor activity. This study was registered at www.clinicaltrials.gov as #NCT02631044.

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Health-Related Quality of Life Outcomes in Patients with Myelodysplastic Syndromes with Ring Sideroblasts Treated with Luspatercept in the Medalist Study

Blood ◽

10.1182/blood-2020-136276 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 10-12

Author(s):

Esther Natalie Oliva ◽

Uwe Platzbecker ◽

Guillermo Garcia-Manero ◽

Ghulam J. Mufti ◽

Valeria Santini ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

Daily Life ◽

Publicly Traded ◽

Advisory Committees ◽

Patient Reported ◽

Eortc Qlq C30 ◽

Eortc Qlq

Introduction: Patients with myelodysplastic syndromes (MDS) experience severe anemia, which is commonly managed with frequent red blood cell transfusions (RBCT) in patients refractory to erythropoiesis-stimulating agents. At diagnosis, 85% of patients have anemia and 30-50% depend on RBCT. The administration of RBCT itself provides transient relief in anemia-related symptoms. Per protocol, MEDALIST investigators were advised to transfuse for symptoms related to anemia at the investigators' discretion. Hence, cessation or reduction of RBCT may increase anemia-related symptoms and negatively impact health-related quality of life (HRQoL). Luspatercept is a first-in-class erythroid maturation agent providing clinically meaningful reduction in transfusion burden in patients with transfusion-dependent anemia due to Revised International Prognostic Scoring System (IPSS-R)-defined Very low-, Low-, or Intermediate-risk MDS with ring sideroblasts in the phase 3 MEDALIST trial (NCT02631070). However, the impact of luspatercept on patients' HRQoL has not been evaluated. This analysis aimed to evaluate the effect of luspatercept versus placebo on HRQoL of patients treated for MDS from baseline through Week 25 of the MEDALIST study. Methods: Patients received luspatercept or placebo every 3 weeks for 24 weeks, plus best supportive care (BSC), including tailored amounts of RBCT. Effects of luspatercept versus placebo on HRQoL were evaluated as secondary and exploratory endpoints in the MEDALIST study. In the primary analysis, mean change from baseline to Week 25 (clinical assessment visit) in the European Organisation for Research and Treatment of Cancer's core quality of life questionnaire, version 3.0 (EORTC QLQ-C30) and in the QoL assessment in MDS questionnaire (QOL-E) was determined using mixed-effects repeated measures analysis. Clinically meaningful change within each treatment arm was defined as a ≥ 10-point change in patient-reported outcome (PRO) score from baseline for all EORTC QLQ-C30 domains, and ≥ 0.5 standard deviation of the baseline domain score for all QOL-E domains. Differences between luspatercept and placebo were considered clinically meaningful if the change from baseline between treatment arms exceeded the threshold for a clinically meaningful difference. In an exploratory analysis, patient-reported impact of transfusion dependence and overall side effects on their daily life was estimated using the QOL-E instrument. Results: A total of 229 patients were randomized; 153 patients to luspatercept and 76 to placebo. The HRQoL-evaluable population, consisting of patients with ≥ 1 post-baseline HRQoL score, was 149 patients in the luspatercept arm and 76 patients in the placebo arm. Questionnaire compliance rates among patients remaining on treatment were similar between luspatercept and placebo treatment groups at Week 25 (EORTC QLQ-C30, 88.2% vs 79.4% and QOL-E, 72.5% vs 69.7%). At baseline, MEDALIST patients had a clinically meaningfully worse HRQoL compared with the general population in 5 of 15 EORTC QLQ-C30 domains: physical functioning, role functioning, social functioning, fatigue, and dyspnea. Through Week 25, there was no clinically meaningful difference in change from baseline between and within the luspatercept and placebo arms across all EORTC QLQ-C30 (Global health status shown in Figure A) and QOL-E domains. A greater proportion of patients in the luspatercept arm relative to placebo reported improvements in daily life from the impact of transfusion burden (Figure B). Relative to baseline, the proportion of patients reporting a lower impact of transfusion dependence on their daily life was 39% versus 22% in luspatercept versus placebo at Week 25; in contrast, the proportion of patients reporting a higher impact of transfusion dependence on their daily life was 12% versus 22% in luspatercept versus placebo. Impact of treatment side effects on patients was comparable between luspatercept and placebo. Conclusions: Luspatercept with BSC reduced RBCT burden and patient-reported transfusion impact on their daily life, while maintaining other aspects of HRQoL from baseline through Week 25 in the MEDALIST study. Disclosures Oliva: Alexion: Consultancy; BMS: Consultancy, Honoraria, Patents & Royalties, Speakers Bureau; Novartis: Consultancy; Amgen: Consultancy; Abbvie: Consultancy; Apellis: Consultancy. Platzbecker:Takeda: Consultancy, Honoraria; Geron: Consultancy, Honoraria; Amgen: Honoraria, Research Funding; BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria. Garcia-Manero:Bristol-Myers Squibb: Consultancy, Research Funding; AbbVie: Honoraria, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; Onconova: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Acceleron Pharmaceuticals: Consultancy, Honoraria; Amphivena Therapeutics: Research Funding; Novartis: Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy; H3 Biomedicine: Research Funding. Mufti:BMS, Novartis: Research Funding; Abbvie, Novartis: Consultancy. Santini:Takeda, Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Acceleron, BMS, Menarini, Novartis: Consultancy; BMS, J&J, Novartis: Honoraria. Sekeres:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda/Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Komrokji:BMS: Honoraria, Speakers Bureau; Acceleron: Honoraria; Geron: Honoraria; Agios: Honoraria, Speakers Bureau; AbbVie: Honoraria; JAZZ: Honoraria, Speakers Bureau; Incyte: Honoraria; Novartis: Honoraria. Shetty:BMS: Current Employment, Current equity holder in publicly-traded company. Tang:BMS: Current Employment, Current equity holder in publicly-traded company. Guo:BMS: Consultancy. Zhang:BMS: Current Employment. Ha:Bristol Myers Squibb: Current Employment. Ito:BMS: Current Employment, Current equity holder in publicly-traded company. Lord-Bessen:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Backstrom:BMS: Current equity holder in publicly-traded company; Acceleron Pharma: Current Employment, Current equity holder in publicly-traded company. Fenaux:Novartis: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding.

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Health State Utility Valuation in Patients with Triple-Class-Exposed Relapsed and Refractory Multiple Myeloma Treated with the Bcma-Directed CAR T Cell Therapy, Idecabtagene Vicleucel (ide-cel, bb2121): Results from the Karmma Trial

Blood ◽

10.1182/blood-2020-136677 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 14-15

Author(s):

Michel Delforge ◽

Nina Shah ◽

Paula Rodriguez-Otero ◽

Parameswaran Hari ◽

Julia Braverman ◽

...

Keyword(s):

Quality Of Life ◽

General Population ◽

Research Funding ◽

Health State ◽

Publicly Traded ◽

Health States ◽

T Cell Therapy ◽

Car T Cell Therapy ◽

Car T

Introduction: Idecabtagene vicleucel (ide-cel, bb2121) is a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cell therapy under investigation in the KarMMa trial as a treatment for patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies. In the phase 2 KarMMa trial, ide-cel demonstrated a favorable benefit-risk profile in this patient population (Munshi NC, et al. J Clin Oncol 2020;38:8503). Ide-cel also demonstrated clinically meaningful improvements in the key health-related quality of life (HRQoL) symptoms associated with MM (Delforge M, et al. HemaSphere 2020;4:EP1000). Translating HRQoL data to health state utility values (HSUVs)/HRQoL weights is key to understanding the HRQoL impact of a treatment in relation to that of a healthy general population and is an important consideration in clinical decision making and health technology assessments. HSUVs are scored between 0 and 1, where 0 is death and 1 is perfect health. In the general population, individuals of a similar age range to patients with MM have HSUV scores of 0.83 in the USA, 0.80 in the UK, and 0.84 in Canada (Guertin JR, et al. CMAJ 2018;190:E155-161; Janssen MF, et al. Eur J Health Econ 2019;20:205-216). This analysis aimed to determine HSUVs for patients treated in the KarMMa study according to their progression status. Methods: HRQoL assessment in the KarMMa study (NCT03361748) included the European Quality of Life-5 dimensions 5 levels (EQ-5D-5L) health state classifier performed at specified time points: prior to receiving lymphodepleting chemotherapy (baseline), day of infusion (Day 1), Months 1, 2, 3, 6, 9, 12, and 15, inclusive of disease progression/relapse or complete remission. Using US, UK, and Canadian weights, HSUVs were estimated for the KarMMa trial at an aggregate level. A longitudinal mixed-effects model was used with health state as a fixed effect, and a random intercept term. Three models were run using different health states. Model 1 considered 3 health states: baseline, pre-progression, and post-progression. In Model 2, the pre-progression health state was split into 2 time periods: Day 1 to the end of Month 1, and Month 2 onward. In Model 3, 2 pre-progression health states were defined based on the quality of response to treatment, thus capturing the difference in HRQoL for patients achieving at least a very good partial response (≥ VGPR) or patients who did not achieve a VGPR (< VGPR). Results: The HSUVs derived from the 3 different models using US, UK, and Canadian tariffs are summarized (Table). In all 3 models, patients in the pre-progression state experienced an increase in HRQoL from baseline. In Model 1, the increment ranged from +0.05 to +0.08. On progression, patients experienced a decrement (−0.01 to −0.03), but their HSUV remained above the baseline value by +0.04 to +0.05, indicating that ide-cel treatment was associated with an improvement in HRQoL, with some of the benefit remaining even upon disease progression. When HSUV in the pre-progression state was analyzed in Model 2 at Month 1 and then Month 2 onward, patients also experienced an increase in their HRQoL from baseline. While this increase was small in Month 1 (+0.02 to +0.04), the subsequent increase from baseline (i.e. from Month 2 onward) was more pronounced (+0.07 to +0.10) reflecting the benefits of a one-off administration of ide-cel and the associated treatment-free interval. A further analysis of the pre-progression HSUV by the quality of response in Model 3 showed that patients who achieved ≥ VGPR had a greater improvement in HRQoL (+0.08 to +0.11) than patients who achieved < VGPR. Both response levels were associated with an improvement in HRQoL compared with baseline, with HRQoL for patients achieving ≥ VGPR approaching that of the general population (Figure). Conclusions: Results of this analysis indicate that ide-cel provides clinically meaningful improvements in HRQoL for patients with triple-class-exposed RRMM. The benefit is particularly marked in patients who achieve ≥ VGPR, in whom HRQoL approaches that of the general population. Disclosures Delforge: Janssen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Takeda: Honoraria; Amgen: Honoraria. Shah:BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy. Rodriguez-Otero:Celgene-BMS: Consultancy, Honoraria; Mundipharma: Research Funding; Janssen, BMS: Other: Travel, accommodations, expenses; BMS, Janssen, Amgen: Honoraria; Janssen, BMS, AbbVie, Sanofi, GSK, Oncopeptides, Kite, Amgen: Consultancy, Honoraria. Hari:Amgen: Consultancy; GSK: Consultancy; Janssen: Consultancy; BMS: Consultancy; Incyte Corporation: Consultancy; Takeda: Consultancy. Braverman:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Trigg:Adelphi Values: Current Employment. Patel:BMS: Current Employment. Huang:BMS: Current Employment, Current equity holder in publicly-traded company. Hege:Arcus Biosciences: Divested equity in a private or publicly-traded company in the past 24 months; Mersana Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; BMS: Current Employment, Current equity holder in publicly-traded company, Other: Travel, accommodations, expenses, Patents & Royalties: Numerous, Research Funding. Dhanasiri:BMS: Current Employment, Current equity holder in publicly-traded company.

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Age and Gender-Related Pretreatment Quality of Life Profiles in Patients with Higher-Risk Myelodysplastic Syndromes. Establishing Benchmark Data from an International Study

Blood ◽

10.1182/blood.v126.23.2099.2099 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2099-2099

Author(s):

Fabio Efficace ◽

Gianluca Gaidano ◽

Massimo Breccia ◽

Pasquale Niscola ◽

Francesco Cottone ◽

...

Keyword(s):

Quality Of Life ◽

Research Funding ◽

Control Groups ◽

Age And Gender ◽

Respective Control ◽

Eortc Qlq C30 ◽

And Gender ◽

Mean Differences ◽

Eortc Qlq

Abstract Background: Patients myelodysplastic syndromes (MDS) diagnosed with higher-risk disease have poor prognosis thus making improvements in health-related quality of life (HRQOL) a major goal of therapy. Understanding HRQOL profile of untreated patients is important to help clinicians to better target subpopulations in need of special attention from the very beginning of therapy. Aims: The primary objective of this study is to investigate whether HRQOL differences exist by age and gender in untreated patients with higher-risk MDS. A secondary objective is to provide age and gender pretreatment HRQOL profiles to be used as reference baseline data for comparing HRQOL of MDS patients under treatments. Methods: This analysis is based on 280 adult patients diagnosed with IPSS risk score of intermediate-2 (74%) and high-risk (26%), enrolled in an international prospective observational study. Median age of patients was 71 years (range 32-89), 176 were men (63%) and 104 (37%) women. HRQOL was assessed at study entry and before treatment for higher-risk disease (except for transfusions), with the EORTC QLQ-C30, the most widely used HRQOL outcome measure in MDS research. Thus, our data are likely to further ease interpretation of outcomes in many studies using this questionnaire. One hundred seventy-five patients had received at least one red blood cell transfusion at the time of baseline HRQOL assessment. HRQoL data of MDS patients were age-gender matched with those general population norms. Wilcoxon-Mann-Whitney and Wilcoxon signed ranks tests were used for unmatched and matched comparisons, respectively (α=0.05). Effect sizes were also computed. Results: No statistically significant differences existed in any of the HRQOL domain by IPSS category (intermediate-2 versus high-risk). However, HRQOL profiles differed by age and gender and results are reported in Table 1. Women generally reported lower HRQOL scores than men, with statistically significant impairments in the global quality of life (P=0.008), role (P=0.014), emotional (P=0.024) and social functioning (P=0.028). When compared to their peers in the general population, HRQOL was found to be impaired in all age group categories (Figure 1, A and B). However, the magnitude of impairments across HRQOL domains was markedly larger in younger patients (aged 30-59 years) compared to older age groups (≥60 years). The top three largest impairments in this younger group were found for: fatigue (ES=2.47, P<0.001), dyspnea (ES=2.14, P<0.001) and role functioning RP (ES=1.96, P<0.001). This latter aspect indicates the ability to perform daily activities. Conclusion: Pretreatment HROQL of higher-risk MDS patients vary by age and gender and current reference data will help making more accurate comparisons with HRQOL of patients under treatment. Clinicians should also pay special attention to younger patients, as these are those most in need of HRQOL improvements. Figure 1. Adjusted mean differences between MDS patients and their respective control groups by age categories (30-59 years, 60-69 years, 70-79 years and over 80) in functional aspects and global quality of life. A score below 0 line means worse outcomes for MDS patients. *= Statistically significant (P<0.05) **= Statistically significant (P<0.001) Figure 1. Adjusted mean differences between MDS patients and their respective control groups by age categories (30-59 years, 60-69 years, 70-79 years and over 80) in functional aspects and global quality of life. A score below 0 line means worse outcomes for MDS patients. / *= Statistically significant (P<0.05) **= Statistically significant (P<0.001) Figure 2. Adjusted mean differences between MDS patients and their respective control groups by age categories (30-59 years, 60-69 years, 70-79 years and over 80) in symptom scales. A score above 0 line means worse outcomes for MDS patients. *=Statistically significant (P<0.05) **=Statistically significant (P<0.001) Figure 2. Adjusted mean differences between MDS patients and their respective control groups by age categories (30-59 years, 60-69 years, 70-79 years and over 80) in symptom scales. A score above 0 line means worse outcomes for MDS patients. / *=Statistically significant (P<0.05) **=Statistically significant (P<0.001) Figure 3. Quality of life profile by the EORTC QLQ-C30 in higher risk-MDS patients by gender and age groups. Means scores of the EORTC QLQ-C30 are reported. Figure 3. Quality of life profile by the EORTC QLQ-C30 in higher risk-MDS patients by gender and age groups. Means scores of the EORTC QLQ-C30 are reported. Disclosures Gaidano: MorphoSys; Roche; Novartis; GlaxoSmithKline; Amgen; Janssen; Karyopharm: Honoraria, Other: Advisory boards; Celgene: Research Funding. Santini:celgene, Janssen, Novartis, Onconova: Honoraria, Research Funding. Platzbecker:Celgene: Honoraria; GlaxoSmithKline: Honoraria, Research Funding; Novartis: Honoraria; Amgen, Inc.: Honoraria. Di Renzo:Celgene: Research Funding.

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

Blood ◽

10.1182/blood-2020-136312 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 8-9

Author(s):

Maria Domenica Cappellini ◽

Ali T. Taher ◽

Antonio Piga ◽

Farrukh Shah ◽

Ersi Voskaridou ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

Publicly Traded ◽

Advisory Committees ◽

Meaningful Improvement ◽

Sf 36 ◽

La Jolla ◽

Domain Scores

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

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Health-Related Quality of Life and Symptoms in Myelofibrosis Patients Treated with Ruxolitinib Versus Best Available Therapy

Blood ◽

10.1182/blood.v118.21.795.795 ◽

2011 ◽

Vol 118 (21) ◽

pp. 795-795

Author(s):

Claire N. Harrison ◽

Jean-Jacques Kiladjian ◽

Haifa Kathrin Al-Ali ◽

Heinz Gisslinger ◽

Laurent Knoops ◽

...

Keyword(s):

Research Funding ◽

Treatment Phase ◽

Well Being ◽

Employment Equity ◽

Advisory Committees ◽

Eortc Qlq C30 ◽

Health Related ◽

Equity Ownership ◽

Eortc Qlq

Abstract Abstract 795FN2 Background: Ruxolitinib (INC424), a potent and selective oral JAK1 and JAK2 inhibitor, demonstrated rapid and durable reductions in splenomegaly and improved disease-related symptoms, role functioning, and quality of life (QoL) in 2 phase 3 studies in patients with myelofibrosis (MF) (the COMFORT studies). Per-protocol, patient-reported, health-related QoL (HRQoL) and symptoms analyses in the COMFORT-II study are limited. Here we report on additional post hoc analyses of these outcomes. The COMFORT-II study includes 219 patients (ruxolitinib, n=146; best available therapy [BAT], n=73). At entry, all patients were classified into intermediate 2-risk or high-risk prognostic groups (Cervantes F, et al. Blood, 2009;113(13):2895-2901) and had palpable splenomegaly ≥5 cm below the costal margin. Patients could have received prior therapy for MF. On BAT, doses and schedules or no therapy were selected by the investigator; therapy adjustments were permitted during the randomized treatment phase at the investigator's discretion. Patients in both arms continued in the randomized treatment phase as long as there was no protocol-defined disease progression. Methods: The European Organisation for the Research and Treatment of Cancer (EORTC) QoL Questionnaire–Core 30 (QLQ-C30) and Functional Assessment of Cancer Therapy–Lymphoma (FACT-Lym) questionnaires were assessed at baseline and weeks 8, 16, 24, and 48. EORTC QLQ-C30 consists of 30 items combined into 15 subscales (Global Health Status/QoL, 5 functioning subscales, and 9 symptom subscales; scores range from 0 to 100, and higher scores indicate better HRQoL and functioning but a worsening of symptoms). FACT-Lym consists of 42 items combined into 8 subscales (4 well-being subscales; 1 symptom subscale [LymS]; and 3 total scale scores: FACT-General [G], FACT-Lym trial outcome index [TOI], and FACT-Lym total; scores for the different subscales vary from 0–28 to 0–168, and higher scores indicate better outcomes). This analysis includes evaluable patients in the randomized treatment phase and assesses changes from baseline in HRQoL and MF symptom scores, including the EORTC subscales, LymS, and FACT total scores, which incorporate well-being and/or symptom subscales. Mixed-model analyses, adjusted for age, sex, baseline score, and prognostic risk category, are used to evaluate treatment differences at each time point and overall across time. Results: HRQoL and MF symptoms, on average, improved compared with baseline for patients receiving ruxolitinib, but remained the same or worsened for patients receiving BAT. Based on the EORTC QLQ-C30, the treatment differences in physical functioning, role functioning, fatigue, and appetite loss significantly favored ruxolitinib starting at week 8 (P <.05) and remained significant at week 48 (P <.05). The overall between-treatment differences (on average across time) in adjusted mean change from baseline for MF symptom scores (95% confidence interval) were: Fatigue, –10.2 (–15.9, –4.5; P <.001); Dyspnea, –11.6 (–17.6, –5.6; P <.001); Appetite loss, –16.3 (–21.5, –11.1; P <.0001); Insomnia, –9.8 (–16.7, –3.0; P <.01); and Pain, –9.0 (–14.9, –3.0), P <.01); negative values favor ruxolitinib. Global Health Status/QoL (Figure) was significantly improved in the ruxolitinib arm compared with the BAT arm at weeks 8, 16, and 48. Scores on the LymS, which includes symptoms of pain, swelling, fever, night sweats, itching, trouble sleeping, fatigue, weight loss, loss of appetite, trouble concentrating, and other patient concerns, also improved significantly during treatment (Figure). Additionally, FACT-G, FACT-Lym TOI, and FACT-Lym total scores were all significantly (P <.05) improved for patients receiving ruxolitinib treatment compared with BAT. Most EORTC QLQ-C30 and FACT-Lym scores improved significantly on ruxolitinib compared with BAT. The treatment effect between the high-risk and intermediate 2-risk prognostic groups was not significantly different based on an analysis of the risk group–by–treatment interaction. Conclusions: These additional analyses from the COMFORT-II study further support that ruxolitinib significantly improves overall HRQoL and MF symptoms compared with BAT. Disclosures: Harrison: Novartis: Honoraria; Incyte: Honoraria; S*Bio: Honoraria; Celgene: Honoraria; Sanofi Aventis: Honoraria. Kiladjian:Novartis: Honoraria; Celgene: Honoraria. Gisslinger:Novartis: Speakers Bureau; Celgene Austria: Research Funding, Speakers Bureau; Aop-Orphan: Speakers Bureau. Knoops:Novartis: Consultancy. Waltzman:Novartis: Employment. Mendelson:Novartis: Employment, Equity Ownership. Zhou:RTI-HS: Employment; Novartis: Research Funding. Copley-Merriman:RTI-HS: Employment; Novartis: Research Funding. Hunter:Incyte Corporation: Employment, Equity Ownership. Levy:Incyte Corporation: Employment, Equity Ownership. Cervantes:Bristol-Myers-Squibb: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Passamonti:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vannucchi:Novartis: Honoraria. Barosi:Novartis: Consultancy.

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Health-related quality of life (HRQoL) in advanced endometrial cancer (aEC) patients (pts) treated with lenvatinib plus pembrolizumab or treatment of physician’s choice (TPC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.5570 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 5570-5570

Author(s):

Domenica Lorusso ◽

Nicoletta Colombo ◽

Antonio Casado Herraez ◽

Alessandro Santin ◽

Emeline Colomba ◽

...

Keyword(s):

Compliance Rate ◽

Primary Analysis ◽

Meaningful Improvement ◽

Treatment Groups ◽

Related Quality ◽

Eortc Qlq C30 ◽

Health Related ◽

Eortc Qlq

5570 Background: In Study 309/KEYNOTE-775, lenvatinib + pembrolizumab (L+P) demonstrated significant and clinically meaningful improvement in OS, PFS, and ORR compared with TPC in aEC pts following prior platinum-based systemic therapy. Given the medical complexity/age of EC pts, QoL analyses are critical, but often under-reported. We present results of pt-reported HRQoL for Study 309/KEYNOTE-775. Methods: Pts were randomized 1:1 to receive lenvatinib 20 mg QD PO + pembrolizumab 200 mg IV Q3W (n=411) or TPC (n=416; doxorubicin 60 mg/m2 IV Q3W or paclitaxel 80 mg/m2 IV QW, 3 wks on/1 wk off). Pt-reported HRQoL was assessed at cycle 1 day 1, day 1 of each subsequent cycle and at time of discontinuation using EORTC QLQ-C30, its EC module QLQ-EN24, and EQ-5D-5L in treated pts who had ≥1 HRQoL assessment available. Higher scores indicate better functioning/QoL (EORTC QLQ-C30, EQ-5D-5L) or worse symptom severity (QLQ-EN24). Changes in EORTC QLQ-C30 global health status (GHS)/QoL was a secondary endpoint. This was analyzed from baseline to the latest timepoint at which overall completion was ≥60% and overall compliance was ≥80%, using constrained longitudinal data analysis; other HRQoL analyses were exploratory. Results: Completion and compliance rates of EORTC QLQ-C30 were >95% in both groups at baseline. Primary analysis was conducted at wk 12 as completion rate was 80% for L+P and 62% for TPC; compliance rate was 93% for L+P and 87% for TPC. Baseline GHS/QoL scores were similar between the L+P group and TPC group: mean (SD) of 65.74 (21.87) vs 65.69 (22.71), respectively. Over 12 wks of follow-up, pts in both groups had slight decreases in GHS/QoL. Similar decreases were observed for pts receiving L+P vs TPC: -5.97 (95% CI: -8.36, -3.58) vs -6.98 (95% CI: -9.63, -4.33). The between-group difference in least-squares (LS) mean score change from baseline to wk 12 for L+P vs TPC was 1.01 points (95% CI: -2.28, 4.31). Over time, QoL scores were generally similar across treatments. Results were similar for other HRQoL endpoints (Table). Conclusions: No significant differences were observed in HRQoL scores between treatment groups. With no standard treatment approach following failure of platinum-based therapy, these data along with previously reported efficacy and safety findings from Study 309/KEYNOTE-775 further support that L+P has an overall favorable benefit/risk profile compared to chemotherapy. Clinical trial information: NCT03517449. [Table: see text]

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Associations Between Improvements in Myelofibrosis (MF) Symptoms and Quality of Life Measures with Splenomegaly Reduction in COMFORT-I: A Randomized, Double-Blind, Phase III Trial of the JAK1 and JAK2 Inhibitor Ruxolitinib Versus Placebo in Patients with MF,

Blood ◽

10.1182/blood.v118.21.3842.3842 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3842-3842 ◽

Cited By ~ 1

Author(s):

Ruben A. Mesa ◽

Jason Gotlib ◽

Vikas Gupta ◽

John F. DiPersio ◽

John Catalano ◽

...

Keyword(s):

Quality Of Life ◽

Placebo Group ◽

Board Of Directors ◽

Research Funding ◽

Phase Iii ◽

Advisory Committees ◽

Jak2 Inhibitor ◽

Eortc Qlq C30 ◽

Eortc Qlq

Abstract Abstract 3842 Background: Dysregulated JAK-STAT signaling is a key feature in MF, which is characterized by splenomegaly, debilitating symptoms, poor quality of life (QoL), cytopenias, and shortened survival. Ruxolitinib is a selective JAK1 and JAK2 inhibitor with clinical activity in MF. COMFORT-I is a Phase III, double-blinded, placebo-controlled study of ruxolitinib in patients with MF. At wk 24, 41.9% of patients receiving ruxolitinib reached the protocol-defined threshold of a ≥35% reduction in spleen volume (SV) compared to 0.7% in the placebo group (p<0.0001). The objective of this analysis was to evaluate the relationship between SV reduction achieved with ruxolitinib treatment and changes in symptoms and QoL. Methods: 309 patients were randomized to receive ruxolitinib (n=155) or placebo (n=154). Initial dosing was based on baseline platelet counts: 15 mg BID for counts of 100–200 x109/L and 20 mg BID for >200 x109/L. SV was measured by blinded imaging (MRI or CT scan) every 12 wks. Via electronic diary, patients reported MF symptoms daily using the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0. The Total Symptom Score (TSS) from the MFSAF represents a combined score for the individual symptoms of abdominal discomfort, pain under ribs on left side, early satiety, itching, night sweats, and bone/muscle pain. The European Organization for Research and Treatment of Cancer Quality-of-Life 30 (EORTC QLQ-C30) and Patient-Reported Outcomes Measurement System (PROMISE) Fatigue questionnaires were administered at each visit; Patient Global Impression of Change (PGIC) was administered at every visit beginning at wk 4. The PGIC rates a patient's overall sense of whether a treatment has been beneficial or not on a 7-point scale, ranging from 1 = very much improved to 7 = very much worse, with 4 = no change. Results: Baseline QoL scores reflected debilitating disease, and were similar to scores for similar-aged patients with other cancers (Scott NW, Fayers PM, Aaronson NK, et al. EORTC QLQ-C30 Reference Values Manual, July 2008). The impact on patients was particularly evident on the PROMIS Fatigue scale and QLC-C30 Global Health, Physical Functioning, Role Functioning, and Social Functioning subscales. Baseline Symptom and QoL Measures* Associations between changes in symptoms and QoL with the objectively measured changes in SV were evaluated. Patients receiving ruxolitinib were grouped according to SV reduction at 24 wks of treatment: ≥35% reduction in SV (n=65), 10-<35% (n=51), and <10% (n=23). Symptom and QoL responses were evaluated among the various subgroups (of the SV reduction percentage strata) and comparisons were made across these and the total placebo group (n=106). Shown in the Figure are mean changes at wk 24 relative to baseline for TSS, QoL indicators, and PGIC scores. Conclusions: Changes in SV as low as 10% in ruxolitinib-treated patients were associated with improvements on EORTC QLQ-C30 Global Health subscale, PROMISE Fatigue scale, and the MFSAF v2.0 diary TSS. Moreover, commensurate improvements in these outcomes were observed as the SV reduction increased. Importantly, the simple PGIC questionnaire allowed patients to characterize a meaningful change in their condition that was consistent with more comprehensive measures of MF symptoms and quality of life, reflecting a doctor-patient assessment easily applied to clinical practice. Disclosures: Mesa: Incyte: Research Funding; Lilly: Research Funding; SBio: Research Funding; Astra Zeneca: Research Funding; NS Pharma: Research Funding; Celgene: Research Funding. Gotlib:Incyte: Consultancy, Research Funding. Gupta:Incyte: 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. Catalano:Incyte: Honoraria; Novartis: Honoraria. Deininger:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Genzyme: Research Funding. Shields:Incyte: Consultancy. Miller:Incyte: Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau. Winton:Incyte: Consultancy. Hare:Incyte: Employment. Erickson-Viitanen:Incyte: Employment. Sun:Incyte: Employment. Sandor:Incyte: Employment. Levy:Incyte: Employment, Equity Ownership. Kantarjian:Incyte: Research Funding; Novartis: Consultancy, Research Funding. Verstovsek:Incyte: Research Funding.

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Effects of a Home-Based Exercise Intervention Program on Physical Capacity and Fatigue in Patients with Myelodysplastic Syndrome (MDS) - a Feasibility Study

Blood ◽

10.1182/blood.v126.23.5609.5609 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5609-5609

Author(s):

Markus K Schuler ◽

Julia Goebel ◽

Beate Hornemann ◽

Julia Hoffmann ◽

Michael Kramer ◽

...

Keyword(s):

Research Funding ◽

Exercise Intervention ◽

Exercise Program ◽

Physical Capacity ◽

Walking Distance ◽

Strength Measurement ◽

Home Based ◽

Eortc Qlq C30 ◽

Eortc Qlq

Abstract Introduction: Cancer-related fatigue (CrF) is a frequent and disabling symptom in hematological malignancies and associated with significant impairment in quality of life (QoL). Patients suffer from tiredness, weakness and limited capability. CrF involves physical, psychological, mental and social aspects, and often leads to inactivity or depressive mood. There is evidence for the benefit of exercise and physical activity on CrF, but clinical trials targeting patients with MDS are missing. Methods: We conducted a prospective, non-randomized trial to assess the feasibility, safety and efficacy of a home-based exercise intervention in patients with IPSS low to intermediate risk MDS. Subjects underwent an introduction and first exercise session at baseline (T0) under supervision of a physiotherapist. Workout sessions were then performed unsupervised in an outpatient setting. Patients were asked to record results in a sports diary. Exercise schedule contained six sessions per week - endurance or strength training in daily turns - over 12 weeks (T1). Follow-up assessment was performed at week 24 (T2). Endurance training included walking, running, cycling or swimming at patient´s preference. Strength training consisted of six exercises with an elastic strap for both upper and lower limb and the spine. Subjects were examined three times (T0, T1, T2). All examinations included 6-minutes walking distance (6-MWD), an ergometer check, isometric strength measurement of lower limb and isokinetic strength measurement of the abdomen and back. Quality of life and fatigue were assessed by the EORTC QLQ-C30 and Multidimensional Fatigue Inventory (MFI). Results: Twenty-one patients (13 male, 8 female) with low to intermediate risk MDS were included. Median age was 66 years (range 29-87). Fifteen patients completed the program at week 12 (T1). Twelve patients voluntarily continued the exercise program until week 24 (T2). The primary endpoint was met, since 11 patients (52%) performed more than 75% of all planned session. Median number of individual workout session was 54 (range 1-72). There were no adverse events reported due to the intervention. Main reasons for missed training sessions were doctor´s appointments or hospitalization, other private appointments, followed by acute infection and general weakness. Six-minute walking distance (6-MWD) improved from 570 meters (m) (T0) to 645 m (T1, +13%) and 660 m (T2, +16%). Among other parameters of physical capacity, strength of lower limbs increased from 2230 Newton (N) (T0) to 2570 (T1, +15%) and 2730 (T2, +22%). Between T0, T1 and T2 most functional measures like global health status (53 vs. 50 vs. 52), role functioning (62 vs. 49 vs. 61) and social functioning (63 vs. 58 vs. 53) were equal or slightly decreased. General fatigue did not significantly change over time (49 vs. 52 vs. 47 using the EORTC QLQ-C30 score [scale 0-100] and 12.2 vs. 12.4 vs. 11.9 on MFI [scale 0-21]. Results of all endurance and resistance parameters and QoL measures including fatigue subscales are displayed in Table 1. Conclusion: These data provide evidence that an unsupervised outpatient exercise program is feasible in MDS patients. The results of this pilot study also demonstrate that patients' acceptance of the program is high and physical capacity can be improved. Fatigue as a predominant symptom did not worsen during observational period. Further studies are therefore warranted. Figure 1. Results of all endurance and resistance parameters and QoL measures including fatigue subscales Figure 1. Results of all endurance and resistance parameters and QoL measures including fatigue subscales Disclosures Schuler: PharmaMar: Research Funding. Ehninger:Cellex GmbH: Equity Ownership. Platzbecker:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Boehringer: Research Funding.

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