scholarly journals 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 ◽  
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.

scholarly journals 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

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3845-3845
Author(s):  
Jeremy S. Abramson ◽  
Scott R. Solomon ◽  
Jon E. Arnason ◽  
Patrick B. Johnston ◽  
Bertram Glass ◽  
...  
Keyword(s):  
Cognitive Functioning ◽  
Research Funding ◽  
Publicly Traded ◽  
Meaningful Improvement ◽  
Car T ◽  
Evaluable Population ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
To Receive

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.

scholarly journals Updated Health-Related Quality of Life Results from the KarMMa Clinical Study in Patients with Relapsed and Refractory Multiple Myeloma Treated with the B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy Idecabtagene Vicleucel (ide-cel, bb2121)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2835-2835
Author(s):  
Michel Delforge ◽  
Nina Shah ◽  
Paula Rodríguez-Otero ◽  
Julia Braverman ◽  
Devender Dhanda ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Health Utility Index ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Meaningful Improvement

Abstract Introduction: Patients with heavily pretreated relapsed and refractory multiple myeloma (RRMM) have poor outcomes and poor health-related quality of life (HRQoL). The B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy ide-cel has shown frequent, deep, and durable responses in patients with RRMM who were triple-class exposed (TCE) to immunomodulatory drugs, proteasome inhibitors (PI), and anti-CD38 monoclonal antibodies in the pivotal, phase 2, single-arm KarMMa trial (Munshi NC, et al. N Engl J Med 2021;384:705-716). Ide-cel is approved in the US by the FDA for the treatment of adults with RRMM after ≥ 4 prior lines of therapy, including an immunomodulatory drug, PI, and anti-CD38 monoclonal antibody. We have shown previously that in the KarMMa trial, ide-cel provides clinically meaningful benefits in HRQoL at 9 months' follow-up (Delforge M, et al. HemaSphere 2020;4(suppl 1). Abstract EP1000; Shah N, et al. Blood 2020;136(suppl 1):28-29). The aim of this analysis was to extend previous reports by analyzing the effect of ide-cel on HRQoL at 24 months post-infusion data cut off (December 21, 2020) in patients with TCE RRMM in the KarMMa trial. Methods: In the KarMMa trial (NCT03361748), eligible patients had ≥ 3 prior antimyeloma treatment regimens, were TCE, and refractory to their last treatment regimen per International Myeloma Working Group criteria. To assess HRQoL, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 (QLQ-C30), EORTC QLQ Multiple Myeloma Module (QLQ-MY20) and EuroQoL 5 dimensions 5 levels (EQ-5D-5L) questionnaires were administered at screening, baseline, at ide-cel infusion, at months 1-6, and every 3-6 months up to month 24 or end of study. Thresholds for clinically meaningful changes from baseline were predefined. Statistical significance was calculated using the 2-sided Wilcoxon signed rank test (0.05 significance level). Results: Of 128 patients treated with ide-cel, 126 (98%) had a baseline and ≥ 1 post-baseline HRQoL assessment and were included in the HRQoL-evaluable population. The patient questionnaire completion rate was ≥ 75% up to month 6 and 50%-70% thereafter for most visits. For the predefined primary HRQoL domains, mean scores improved after ide-cel treatment and were comparable to the general population (Table). Mean changes from baseline exceeded the minimal important difference (MID) threshold for clinically meaningful improvement in fatigue, pain, physical functioning, cognitive functioning, and global health status/quality of life (QoL) scores of QLQ-C30 and disease symptom scores of QLQ-MY20 through month 24 (data cutoff, December 21, 2020). Side effects of treatment (QLQ-MY20) remained stable. Overall, 40%-70% of patients had clinically meaningful improvements in the QLQ-C30 fatigue, pain, physical functioning, and global health status/QoL scores at later timepoints. Moreover, 30%-40% of patients experienced clinically meaningful improvements in cognitive functioning, disease symptoms, and side effects, with 40%-60% of patients remaining stable in these domains, across most of the post-baseline assessment visits. Predefined secondary HRQoL domains included all other domains from QLQ-C30 and -MY20, EQ-5D-5L health utility index scores, and EQ-5D visual analogue scale (VAS) scores. Mean changes from baseline exceeded the MID thresholds for clinically meaningful improvement and reached statistical significance across most follow-up visits for role functioning, emotional functioning, social functioning, dyspnea, insomnia, constipation, diarrhea (QLQ-C30), future perspectives (QLQ-MY20), health utility index scores (EQ-5D-5L), and VAS scores (EQ-5D). Mean changes from baseline for nausea/vomiting, appetite loss, financial difficulties (QLQ-C30), and body image (QLQ-MY20) scores were not clinically meaningful. At the individual level, most patients remained stable or achieved clinically meaningful improvements in secondary domains of interest across almost all follow-up visits. Conclusion: In this study, patients with TCE RRMM who received a single infusion of ide-cel showed clinically meaningful improvements across multiple HRQoL domains during the 24-month follow-up period. Figure 1 Figure 1. Disclosures Delforge: Bristol Myers Squibb: 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. Shah: Sanofi: Consultancy; Sutro Biopharma: Research Funding; Janssen: Research Funding; Oncopeptides: Consultancy; Kite: Consultancy; Indapta Therapeutics: Consultancy; Poseida: Research Funding; Nektar: Research Funding; Precision Biosciences: Research Funding; Karyopharm: Consultancy; GSK: Consultancy; CareDx: Consultancy; BMS/Celgene: Research Funding; Bluebird Bio: Research Funding; CSL Behring: Consultancy; Amgen: Consultancy; Teneobio: Research Funding. Rodríguez-Otero: Sanofi: 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, Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy; Janssen, Celgene, Amgen, Oncopeptides, Sanofi, Abbvie, GlaxoSmithKline, Kite Pharma: Consultancy, Honoraria, Speakers Bureau; Regeneron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Braverman: BMS: Current Employment, Current equity holder in publicly-traded company. Dhanda: BMS: Current Employment, Current equity holder in publicly-traded company. Shi: Bristol Myers Squibb: Consultancy. Guo: Bristol Myers Squibb: Consultancy; Daiichi Sankyo: Consultancy; UCB: Consultancy; Janssen: Consultancy; Gilead: Consultancy; EMD Serono: Consultancy; Evidera: Current Employment. Yu: Evidera: Current Employment. Liao: Evidera: Current Employment. Campbell: Bristol Myers Squibb: Current Employment, Current holder of individual stocks in a privately-held company. Munshi: Legend: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy; Adaptive Biotechnology: Consultancy; Novartis: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Takeda: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy.

scholarly journals 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 ◽  
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.

scholarly journals Quality-of-Life Outcomes in Patients with Relapsed or Refractory Multiple Myeloma Treated with Elotuzumab Plus Lenalidomide/Dexamethasone or Lenalidomide/Dexamethasone: Final Analysis of the Phase 3 ELOQUENT-2 Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2190-2190 ◽  
Author(s):  
David Cella ◽  
Jan McKendrick ◽  
Harrison Davis ◽  
Ravi Vij ◽  
Clara Chen
Keyword(s):  
Quality Of Life ◽  
Global Health ◽  
Research Funding ◽  
Final Analysis ◽  
Pain Severity ◽  
Global Health Status ◽  
Treatment Groups ◽  
Eortc Qlq

Introduction: The development of numerous novel therapies for the treatment of relapsed or refractory multiple myeloma (MM) has resulted in improved response rates and durable responses that prolong survival. Assessment of health-related quality of life (HRQoL) has therefore become increasingly important as HRQoL decreases with increasing lines of therapy (LoTs) (Despiégel et al. Clin Lymphoma Myeloma Leuk 2019). In the phase 3 ELOQUENT-2 study (NCT01239797), elotuzumab (E) plus lenalidomide/dexamethasone (Ld) showed a 30% reduction in the risk of progression/death versus Ld in patients with relapsed or refractory MM and 1-3 prior LoTs (median follow-up: 24.5 months; Lonial et al. N Engl J Med 2015). The initial analysis of patient-reported outcomes (PROs) from ELOQUENT-2 at a 3-year extended follow-up showed that the improvement in efficacy observed with ELd was achieved without a detriment to HRQoL (Cella et al. Ann Hematol 2018). Here we present the final analysis of PRO data from ELOQUENT-2. Methods: In ELOQUENT-2, patients with relapsed or refractory MM and 1-3 prior LoTs were randomized 1:1 to receive ELd or Ld in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The Brief Pain Inventory-Short Form (BPI-SF; pain severity, pain interference, and worst pain), the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 questionnaire (QLQ-C30; prespecified key domains were physical function, fatigue, global health status/QoL, and pain), and the myeloma-specific module (QLQ-MY20; includes assessment of symptoms and treatment side effects) were administered at baseline (BL), on Day 1 of each treatment cycle, and at the end of treatment/study withdrawal. All randomized patients with ≥1 post-BL assessment were included in each PRO analysis. Overall mean change from BL was compared between treatment groups based on a mixed-effect model for repeated measures; statistical tests for the overall population only included treatment cycles with >30 patients in each treatment group. A paired t-test was used to compare scores at each cycle with BL; an unpaired t-test compared mean values between treatment groups. BPI-SF scores range from 0-10 with lower scores representing better pain outcomes. EORTC QLQ-C30 scores range from 0-100 with higher scores representing better physical functioning and global health status/QoL, and worse fatigue and pain; EORTC QLQ-MY20 scores range from 0-100 with higher scores representing worse symptoms and problems. Results: In total, 646 patients were treated with ELd (n=321) or Ld (n=325); 319 and 311 patients had ≥1 post-BL assessment and were included in the PRO analysis, respectively (minimum follow-up: 70.6 months). BL BPI-SF mean scores for ELd versus Ld were low across all domains: pain severity (2.6 vs 2.9), pain interference (2.5 vs 2.8), and worst pain (3.6 vs 3.8). Scores for all BPI-SF domains remained stable over the course of the study (eg, pain severity: Figure A). ELd-treated patients with BL moderate/severe pain severity (score of ≥5) had significantly lower mean pain severity scores versus Ld-treated patients in Cycles 1-5. A higher proportion of clinical responders (complete or partial response per European Group for Blood and Marrow Transplantation criteria) versus non-responders had a sustained reduction in pain score across all BPI-SF domains: pain severity (18% vs 6%), pain interference (15% vs 6%), and worst pain (30% vs 13%); the difference in time to sustained improvement was not statistically significant between the clinical responders and non-responders for any pain endpoint. For both treatment groups, there was no clinically meaningful change (≥10 points) from BL scores at any cycle (>30 patients) across all key domains for EORTC QLQ-C30 (eg, global health status/QoL: Figure B) and QLQ-MY20. Conclusions: This final analysis of PROs in ELOQUENT-2 confirms that the efficacy benefits observed with addition of elotuzumab to Ld in patients with relapsed or refractory MM treated with 1-3 prior LoTs were achieved without negatively affecting HRQoL compared with Ld. Study support: BMS. Medical writing: Kenny Tran, Caudex, funded by BMS. Disclosures Cella: FACIT.org: Equity Ownership. McKendrick:PRMA Consulting Ltd.: Employment, Other: I am employed by PRMA Consulting Ltd who provide consulting services to a number of pharmaceutical companies. Davis:PRMA Consulting Ltd.: Employment, Other: I am employed by PRMA Consulting Ltd who provide consulting services to a number of pharmaceutical companies.. Vij:Sanofi: Honoraria; Karyopharm: Honoraria; Janssen: Honoraria; Genentech: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Takeda: Honoraria, Research Funding. Chen:Bristol-Myers Squibb: Employment.

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

Blood ◽  
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.

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

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.

scholarly journals The Impact of the COVID-19 Pandemic on Quality of Life in Danish Patients with Multiple Myeloma; Results from an Ongoing Longitudinal National Survey

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1638-1638
Author(s):  
Louise Redder ◽  
Sören Möller ◽  
Anna Thit Johnsen ◽  
Mary Jarden ◽  
Christen lykkegaard Andersen ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Research Funding ◽  
Statistical Significance ◽  
P Value ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
The Impact ◽  
Second Wave

Abstract Background: The severe, acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), leading to coronavirus-19 (COVID-19), was detected for the first time in Wuhan, China in December 2019. In general, governments and health authorities have taken precautions during the COVID-19 pandemic to reduce viral spread and protect vulnerable citizens. Patients with multiple myeloma (MM) have an increased risk of being infected with COVID-19 and developing a fatal course due to the MM-related immunodeficiency (Glenthøj, A et al. PMID: 32939853). To some extent, the COVID-19 pandemic has changed standard of care towards extended use of oral regimens and limiting hospital visits (Terpos E et al.PMID: 32444866). We aimed to investigate the quality of life (QoL) of Danish patients with MM during the COVID-19 pandemic. We hypothesized that patients living alone and those under the age of 65 years, as a consequence of the pandemic, would experience impaired QoL due to social isolation and fear of infection with SARS-CoV-2. Methods: The Danish prospective, nation-wide, observational survey "Quality of life in Danish patients with multiple myeloma" (QoL-MM) (Nielsen LK et al. PMID: 30656677) framed our study. In QoL-MM, survey data are obtained at enrolment and subsequently at 12 follow-up time points over a two-year period. The following PRO questionnaires are used; the cancer-generic instrument of European Organisation for Research and Treatment of Cancer Quality of life (EORTC) QLQ-C30 (EORTC QLQ-C30), the Multiple Myeloma module QLQ-MY20 (EORTC QLQ-MY20), the Chemotherapy-Induced Peripheral Neuropathy module (EORTC QLQ-CIPN20) and the Short-form health survey version 2 (SF12v2). In the present study, a subpopulation of the QoL-MM cohort was constructed, based on the response time of the questionnaires. QoL was compared using patient-reported outcome (PRO) data obtained before and during the COVID-19 pandemic at group level. In a Danish context, first wave was defined as April to June 2020 and the second wave as November 2020 to January 2021. The QoL data were analyzed using mixed effects linear regression, with a year-period-interaction. Pre-COVID versus COVID mean domain score difference was considered evident, if the difference was both statistically significant (p-value <0.05) and clinically relevant, using minimal important difference (MID) defined as 0.3 standard deviation of the mean score. Results: The study included 616 patients (63% newly diagnosed and 37% relapsed) with a mean age of 68.2 years (standard deviation, 9.2); 40% were females; 76% were married/cohabiting, and 24% single. Questionnaire completion rates during the investigated periods were between 96% and 97%. In total, 1,685 completed sets of questionnaires were included in the analyses. The patients reported no statistically significant and clinically relevant difference in QoL during the first and second waves of the COVID-19 pandemic, compared to one year earlier, see table 1. When analyzing the subpopulations, we found that patients below 65 years reported improved physical health summaries (p-value 0.016), decreased fatigue (p-value < 0.001), less insomnia (p-value 0.002) and improved role functioning (p-value <0.001) during the first wave, reaching both statistical significance and the threshold of MID. The group of patients living alone reported improved role functioning during the first wave, reaching both statistical significance (p-value <0.001) and the threshold of MID. These findings were not evident during the second wave, see table 1. Conclusion: As a group, Danish patients with MM did not report impaired QoL during the COVID-19 pandemic. In contrary, we observed improvements in some domains in patients below 65 years. Our observations indicate that the patients with MM have felt cared for and in good hands during the first and second waves of the COVID-19 pandemic. However, part of the reason for our finding of no negative impact on QoL by the pandemic could be that the questionnaires used were not developed to capture the impact of the pandemic on QoL. Importantly, our results suggest that QoL data collected in clinical trials during the pandemic allow interpretation without adjusting for the impact of the pandemic. Figure 1 Figure 1. Disclosures Redder: Janssen-Ciliag: Research Funding. Frederiksen: Alexion: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding; Novartis: Research Funding.

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

Blood ◽  
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.

scholarly journals The course of peripheral neuropathy and its association with health-related quality of life among colorectal cancer patients

2020 ◽  
Author(s):  
Cynthia S. Bonhof ◽  
Lonneke V. van de Poll-Franse ◽  
Dareczka K. Wasowicz ◽  
Laurens V. Beerepoot ◽  
Gerard Vreugdenhil ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Peripheral Neuropathy ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related ◽  
Eortc Qlq ◽  
The Impact

Abstract Purpose To gain more insight into the course of chemotherapy-induced peripheral neuropathy (CIPN) and its impact on health-related quality of life (HRQoL) in a population-based sample of colorectal cancer (CRC) patients up to 2 years after diagnosis. Methods All newly diagnosed CRC patients from four hospitals in the Netherlands were eligible for participation in an ongoing prospective cohort study. Patients (n = 340) completed questions on CIPN (EORTC QLQ-CIPN20) and HRQoL (EORTC QLQ-C30) before initial treatment (baseline) and 1 and 2 years after diagnosis. Results Among chemotherapy-treated patients (n = 105), a high sensory peripheral neuropathy (SPN) level was reported by 57% of patients at 1 year, and 47% at 2-year follow-up, whereas a high motor peripheral neuropathy (MPN) level was reported by 47% and 28%, at years 1 and 2, respectively. Linear mixed model analyses showed that SPN and MPN symptoms significantly increased from baseline to 1-year follow-up and did not return to baseline level after 2 years. Patients with a high SPN or MPN level reported a worse global quality of life and a worse physical, role, emotional, cognitive, and social functioning compared with those with a low SPN or MPN level. Conclusions Future studies should focus on understanding the mechanisms underlying CIPN so targeted interventions can be developed to reduce the impact of CIPN on patient’s lives. Implications for cancer survivors Patients need to be informed of both CIPN and the impact on HRQoL.

FOENIX-CCA2 quality of life data for futibatinib-treated intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 fusions/rearrangements.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4097-4097
Author(s):  
Juan W. Valle ◽  
Antoine Hollebecque ◽  
Junji Furuse ◽  
Lipika Goyal ◽  
Funda Meric-Bernstam ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Health Status ◽  
Global Health ◽  
Global Health Status ◽  
Phase 2 ◽  
Life Data ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Eq Vas

4097 Background: In FOENIX-CCA2 (NCT02052778), a pivotal phase 2 study among iCCA patients (pts) with FGFR2 fusions/rearrangements, the highly selective, irreversible FGFR1–4 inhibitor futibatinib demonstrated a confirmed objective response rate of 41.7%, with a 9.7-month median duration of response. Adverse events were manageable with dosing modifications that did not adversely impact on response. We report outcomes for the preplanned analysis of Patient-Reported Outcomes (PROs) during futibatinib treatment as a secondary objective of FOENIX-CCA2. Methods: Pts enrolled in FOENIX-CCA2 had locally advanced/metastatic unresectable iCCA with FGFR2 fusions/rearrangements, ≥1 prior line of therapy (including gemcitabine/cisplatin) and ECOG PS 0-1. Pts received oral futibatinib 20 mg continuous QD dosing per 21-day cycle. PRO measures included EORTC-QLQ-C30 (1 global health, 5 functional, 9 symptom scales), EQ-5D-3L, and EQ visual analogue scale (VAS). PROs were collected at screening, cycles 2 and 4, every 3 cycles thereafter, and end of treatment. PRO data were evaluated up to cycle 13, the last visit before data were missing for >50% of the PRO population (PRO primary assessment time point). Results: 92/103 (89.3%) pts enrolled had PRO completion data at baseline and a minimum of 1 follow-up assessment (median age 58 y, 56.5% female), with 48 pts having PRO data at cycle 13. At baseline, mean (SD) EORTC QLQ-C30 global health status score was 70.1 (19.4) and EQ VAS score 71.7 (20.3). Mean EORTC QLQ-C30 global health status scores were maintained from baseline to cycle 13, corresponding to 9.0 months on treatment, with no clinically meaningful (≥10-point) changes in individual functional measures (Table). EORTC QLQ-C30 scores across individual symptom measures were also stable from baseline through cycle 13; only constipation showed an average of 10.0-point worsening at only cycle 4. Mean EQ VAS scores were sustained from baseline to cycle 13 (mean change ranging -1.8 to +4.8 across cycles), with values maintained within the population norm range from across 20 countries. Conclusions: Quality of life data from the phase 2 FOENIX-CCA2 trial show that physical, cognitive and emotional functioning, and overall health status were maintained among pts with advanced iCCA receiving futibatinib. Clinical trial information: NCT02052778. [Table: see text]

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