scholarly journals Quality of Life and Karnofsky Performance Status in Patients with Relapse or Refractory Primary Central Nervous System Lymphoma during Phase I/II Study of Tirabrutinib

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4561-4561
Author(s):  
Yasuhito Terui ◽  
Yoshitaka Narita ◽  
Motoo Nagane ◽  
Kazuhiko Mishima ◽  
Yoshiki Arakawa ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Central Nervous System Lymphoma ◽  
Advisory Committees ◽  
Chugai Pharmaceutical ◽  
Eortc Qlq C30 ◽  
Eortc Qlq

Abstract Background: Based on the results of a phase I/II study in Japan (Trial registration: JapicCTI-173646), tirabrutinib (TIR), a second-generation inhibitor of Bruton's tyrosine kinase, was approved in March 2020 for the treatment of relapsed or refractory primary central nervous system lymphoma (r/r PCNSL). We have previously reported overall response rate of 63.6% and manageable safety profile results of this study (Narita et al. Neuro Oncol. 2021;23(1):122-133). Further, one-year follow-up data after the last patient had enrolled showed that the effects of TIR persisted in r/r PCNSL patients (Mishima et al. Poster presented at the Society for Neuro-Oncology virtual conference; November 19-21, 2020). Here, based on this one-year follow-up data, we describe the Quality of Life (QoL) and Karnofsky Performance Status (KPS) in r/r PCNSL patients treated with TIR. Methods: Patients with r/r PCNSL, age ≥20 years, and KPS ≥70 were treated with TIR once daily (QD) at a dose of 320 mg, 480 mg, or 480 mg upon fasting (480 mg fasted QD). TIR was administered in 28-day cycles, and treatment was continued until disease progression or clinically unacceptable toxicity was observed. QoL was assessed using questionnaires issued by the European Organization for Research and Treatment of Cancer (EORTC), namely QLQ-C30 (EORTC QLQ-C30), EORTC QLQ-BN20, and EuroQol 5 dimensions 3-level (EQ-5D-3L). The QoL survey was conducted during the screening period, on Day 28 of Cycle 1, after every 2 cycles (i.e., after Day 1 of Cycle 3), after every 4 cycles (i.e., after Day 1 of Cycle 25), and at the end of treatment. KPS was measured during the screening period, on days 1, 8, 15, and 28 of Cycle 1, on day 1 of every cycle after Cycle 3, and at the end of treatment. Results: Forty-four patients were prospectively enrolled, and 20, 7, and 17 patients were treated with TIR at 320 mg QD, 480 mg QD, and 480 mg fasted QD, respectively. Median patient age was 60 years (range 29-86). Median follow-up period was 14.9 months (range, 1.4-27.7) for the entire cohort but was 19.1 months, 23.5 months, and 12.0 months for the 320 mg QD, 480 mg QD, and 480 mg fasted QD groups, respectively. At the time of data cutoff (February 25, 2020), 11 patients (25%) remained on treatment. Mean (SD) score for the global health status/QoL section of the EORTC QLQ-C30 was 50.9 (23.7) at baseline and remained relatively constant during treatment (Figure 1). This trend was also observed for emotional function, cognitive function, and fatigue sections of the EORTC QLQ-C30, for motor dysfunction, communication deficit, weakness of legs, and bladder control sections of the EORTC QLQ-BN20, and in items pertaining to self-care, usual activities, and anxiety/depression in the EQ-5D-3L. Median KPS was 80.0 (range, 70-100) at baseline, which remained unchanged during TIR treatment (Figure 2). Conclusion: QoL and KPS scores in r/r PCNSL patients were maintained during TIR administration, a new treatment option for r/r PCNSL, which does not lead to the deterioration of QoL and KPS. Figure 1 Figure 1. Disclosures Terui: Ono Pharmaceutical: Speakers Bureau; MSD: Speakers Bureau; Janssen: Speakers Bureau; Esai: Speakers Bureau; Chugai Pharmaceutical: Speakers Bureau; Celgene: Speakers Bureau; AbbVie: Speakers Bureau; Takeda Pharmaceutical: Speakers Bureau. Narita: Ono Pharmaceutical co.: Honoraria, Research Funding; Dainippon-Sumitomo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Honoraria, Research Funding; Stella-pharma: Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Bayer: Research Funding; Ohara: Research Funding; Chugai Pharmaceutical co.: Honoraria; Novocure: Honoraria. Nagane: AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Honoraria, Research Funding; Pfizer: Research Funding; MSD: Research Funding; Astellas: Research Funding; Nippon-Kayaku: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; Shionogi: Research Funding; Otsuka: Research Funding; Ono Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novocure: Honoraria; Sumitomo Dainippon Pharma: Honoraria; RIEMSER: Membership on an entity's Board of Directors or advisory committees. Mishima: Ono Pharmaceutical Co: Research Funding; Astellas: Research Funding; HOYA Technosurgical Co.: Research Funding; Daiichi-Sankyo: Research Funding; AbbVie: Research Funding; Medical U and A: Research Funding; Teijin Pharma: Research Funding; Eisai: Research Funding; MSD: Research Funding; Chugai: Research Funding. Arakawa: Sanofi: Research Funding; Carl Zeiss: Honoraria, Research Funding; Brainlab: Honoraria, Research Funding; Nihon Medi-Physics: Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Philips: Research Funding; Siemens: Research Funding; Tanabe Mitsubishi: Research Funding; Chugai: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Meiji Seika: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Stryker: Research Funding; Astellas Pharma: Research Funding; Taiho Pharma: Research Funding; Nippon Kayaku: Honoraria; Novocure: Honoraria; UCB Japan: Honoraria; Integra Japan: Honoraria; Otsuka: Honoraria; Abbvie: Honoraria. Yonezawa: Eisai: Speakers Bureau; Ono Pharmaceutical co.: Speakers Bureau; Chugai Pharmaceutical co.: Speakers Bureau. Fukuhara: Celgene: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Eisai: Honoraria; HUYA Bioscience International: Honoraria; Incyte: Research Funding; Janssen: Honoraria; Kyowa Kirin: Honoraria; Nippon Shinyaku: Honoraria; Novartis: Honoraria; Ono Pharmaceutical: Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria; Zenyaku Kogyo: Honoraria; Bayer: Research Funding; AbbVie: Honoraria. Sugiyama: Daichi Sankyo Inc.: Consultancy; Ono Pharmaceutical Inc: Honoraria. Aoi: Ono Pharma USA, Inc.: Current Employment. Nishikawa: Novocure: Consultancy; Chugai: Honoraria, Research Funding; MSD: Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Ono: Honoraria; Nihon-Kayaku: Honoraria. OffLabel Disclosure: Tirabrutinib. Clinical trial for PCNSL.

scholarly journals Azacitidine for Post-Remission Therapy in Elderly Patients with Acute Myeloid Leukemia : Final Results of the Qoless AZA-Amle Randomized Trial

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 117-117
Author(s):  
Esther Natalie Oliva ◽  
Anna Candoni ◽  
Prassede Salutari ◽  
Francesco Di Raimondo ◽  
Gianluigi Reda ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Effect Modification ◽  
Intensive Chemotherapy ◽  
Consolidation Chemotherapy ◽  
Advisory Committees ◽  
Eortc Qlq C30 ◽  
The Difference ◽  
Eortc Qlq

Background: Elderly patients with acute myeloid leukemia (AML) experience a low complete remission (CR) rate following intensive chemotherapy, a short duration of CR and high treatment-related mortality. Median survival is 7-12 months. Several reports suggest that maintenance therapy may improve survival. In particular, a recent report (Huls G, et al. Blood 2019) has shown that azacitidine (Aza) maintenance treatment improves 1-year disease-free survival (DFS) when adjusted for cytogenetics at diagnosis and platelet (PLT) count at randomization. Aims: This phase III, randomized, multicenter trial assesses the efficacy of post-remission Aza treatment versus best supportive care (BSC) in 54 AML subjects >60 years of age in CR after homogeneous induction and consolidation chemotherapy. Primary endpoint is the difference in DFS at 2 and 5 years between arms; main secondary endpoints are the difference in overall survival (OS), the number and length of hospitalizations and quality of life (QoL). Methods: AML subjects with >30% blasts, "de novo" or evolving from myelodysplastic syndrome and fit for intensive chemotherapy, received 2 courses of "3+7" therapy (daunorubicin 40 mg/m2 daily days 1-3 and cytarabine 100 mg/m2 daily IV infusion days 1-7). Subjects obtaining a CR received cytarabine 800 mg/m2 3 hour infusion bid days 1-3 and were randomized 1:1 to receive BSC or Aza at 50 mg/m2 s.c./i.v. for 7 days every 28 days and dose increase after 1st cycle to 75 mg/ m2 for further 5 cycles, followed by cycles every 56 days for 4.5 years or until relapse. QoL was assessed by QOL-E and EORTC QLQ-C30. Results: 149 subjects were included of median age 69, interquartile range (IQR) 65-74 years, and male/female 78/71. Amongst subjects not reaching randomization, 59 were relapsed/refractory, 22 died, 10 refused to continue, 3 were excluded for protocol violation, and 1 was lost to follow-up. Randomized patients (27 Aza, 27 BSC) were in study until relapse. Median follow-up was 9.9 months (IQR: 3.2-22.5). At 2 years post-randomization, no deaths occurred and 21 subjects in the BSC arm (median DFS 9 months, 95% CI 0-20) relapsed versus 18 subjects in the Aza arm (median DFS 11 months, 95% CI 1-21; P=0.33; Fig.1a). There was an effect modification by age on the effect of Aza versus BSC on relapse (P for effect modification=0.02) so that the effect of AZA was not significant for subjects <65 years and 65-73 years (P=0.65 and P=0.66, respectively) but was significant in subjects >73 years (P=0.008, Fig.1b). Cytogenetic risk (P=0.84), minimal residual disease (P=0.97), and platelet (PLT) count (below/above 100 Gi/L, P=0.47) did not modify the effect of Aza on DFS. However, cytogenetic risk and PLT count were confounders: after data adjustment, the effect of Aza on DFS just failed to reach statistical significance [HR (Aza vs BSC): 0.53, 95% CI: 0.26-1.05, P=0.068] . At 5 years post-randomization, no subjects died; 2 subjects on Aza and 1 subject on BSC withdrew consent and 1 subject on Aza in CR withdrew for relapse of bladder cancer. In the BSC arm, 23 subjects relapsed (median DFS 9 months, 95% CI: 0-20) versus 20 Aza subjects (median 11 months, 95% CI: 1-21; P=0.31, Fig.1a).Similar to 2 years post-randomization, at 5 years post-randomization an effect modification by age on the effect of Aza versus BSC was confirmed (P for effect modification=0.01) and the effect of Aza was significant only in subjects >73 years of age (P=0.007, Fig.1b). Again, data adjustment for cytogenetic risk and PLT count strengthened the link between Aza and DFS [HR: 0.56, 95% CI: 0.29-1.07, P=0.08]. Grade 3-4 adverse events (mainly neutropenia) were more frequent in the Aza (41%) than in the BSC arm (4%, P=0.002). Two Aza subjects were hospitalized twice for adverse events for a total of 22 and 26 days, respectively, versus no hospitalization for BSC subjects. QOL-E scores were poor at diagnosis and improved significantly at randomization, with further improvement for physical well-being. EORTC QLQ-C30 symptoms improved progressively over time. In linear mixed model analyses, no significant effect of Aza versus BSC was found for any QoL domain, confirming safety of Aza versus BSC. Summary/Conclusion: With the limitation of a small trial, we conclude that post-remission Aza in elderly AML patients receiving standard induction-consolidation chemotherapy is safe and is well-tolerated. Noteworthy, in patients over 73 years of age, Aza significantly prolongs DFS up to 5 years. Figure Disclosures Oliva: Celgene Corporation: Consultancy, Honoraria, Speakers Bureau; Apellis: Consultancy; Novartis: Consultancy, Speakers Bureau. Candoni:Merck SD: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Celgene: Honoraria; Pfizer: Honoraria; Janssen: Honoraria. Di Raimondo:Takeda: Consultancy; Amgen: Consultancy, Honoraria, Research Funding. Musto:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mannina:Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Martino:Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Bristol myers squibb: Membership on an entity's Board of Directors or advisory committees. Alati:Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

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

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2196-2196
Author(s):  
Hubert Schrezenmeier ◽  
Austin G. Kulasekararaj ◽  
Lindsay Mitchell ◽  
Regis Peffault De Latour ◽  
Timothy Devos ◽  
...  
Keyword(s):  
Rare Disease ◽  
Board Of Directors ◽  
Clinical Outcomes ◽  
Research Funding ◽  
Advisory Committees ◽  
Clinical Variables ◽  
Patient Reported ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Support Research

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

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 ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3842-3842 ◽  
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.

Relationship Between Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) and Efficacy in Patients with Myelofibrosis in the Phase III Persist-1 Trial of Pacritinib Vs. Best Available Therapy (BAT)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1609-1609
Author(s):  
Ruben A. Mesa ◽  
Claire N. Harrison ◽  
Francisco Cervantes ◽  
James P. Dean ◽  
Lixia Wang ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Off Label Use ◽  
Employment Equity ◽  
Advisory Committees ◽  
Off Label ◽  
Eortc Qlq C30 ◽  
Night Sweats ◽  
Equity Ownership ◽  
Eortc Qlq

Abstract Introduction: Myelofibrosis (MF) is a life-threatening hematologic malignancy characterized by splenomegaly and debilitating symptoms including fatigue, abdominal pain, night sweats, bone pain, pruritus, and unintentional weight loss. The myeloproliferative neoplasm symptom assessment form (MPN-SAF) is a PRO tool designed to measure MF-related symptom burden and was developed and validated at Mayo Clinic. It was modified (MPN-SAF total symptom score [TSS] and TSS 2.0) for use in the PERSIST-1 and PERSIST-2 phase 3 trials. For PERSIST-1, when examining the 6 common symptoms in both TSS versions (tiredness, night sweats, early satiety, itchiness, bone pain, and abdominal pain), pacritinib-treated patients (pts) had significant improvements in TSS overall and in individual symptoms vs BAT; Pt Global Impression of Change (PGIC) was also significantly improved for pts receiving pacritinib. Improvements in EORTC-QLQ-C30 scales were noted in the pacritinib arm (Mesa, EHA 2015). The proportion of pts achieving spleen volume reduction (SVR) ≥35% at Week 24 was significantly greater with pacritinib vs BAT (ITT: 19.1% vs 4.7%, p=0.0003; evaluable at baseline and Week 24: 25.0% vs 5.9%; p=0.0001). This analysis examines relationships between TSS improvement and changes in splenomegaly and HRQoL outcomes. Methods: Pts who received no prior JAK inhibitor therapy were randomized 2:1 to oral pacritinib 400 mg once daily or BAT. Pts were stratified by DIPSS risk (Int-1/Int-2 vs High) and platelet count (<50,000/μL vs 50,000/μL to <100,000/μL vs ≥100,000/μL). Pts must have had a baseline total TSS ≥13 using MPN-SAF TSS 2.0. Each symptom is rated on a scale from 0 (absent) to 10 (worst imaginable) using MPN-SAF TSS and TSS 2.0. Results for the 6 symptoms common to both TSS versions are reported. Additional PROs used for assessment of HRQoL included EORTC QLQ-C30 and EQ-5D-5L. In multivariate logistic regressions, odds of TSS reduction ≥50% at Week 24 were modeled as a function of Week 24 SVR ≥35%, spleen length reduction (SLR) ≥ 50%, PGIC, improvement in each EORTC scale, and improvement in EQ-5D-5L Overall Health State (OHS) and in each dimension individually while adjusting for treatment (pacritinib vs BAT). Correlations were examined in all pts and by baseline platelet counts (<50,000/μL, <100,000/μL, and ≥100,000/μL). Results: A total of 327 pts were enrolled (PAC: 220, BAT: 107). 62% of pts had primary MF, 32% had baseline platelets <100,000/μL, and 16% had baseline platelets <50,000/μL. TSS reduction ≥50% was found to be associated with SVR ≥35% and improvement in splenomegaly (SLR ≥50%). In the total pt population, there was a significant association between TSS reduction and SVR (odds ratio [OR]=2.60, p=0.016). In all pts, there was a significant association between TSS reduction and improvements in OHS as measured by EQ-5D-5L (OR=2.30, p=0.013). TSS reductions were also marginally associated with improvements in the QLQ-C30 Global Health Scale (GHS)/QoL Scale (OR=1.92, p=0.050) and, though not statistically significant, there was a trend of improvement in perceived overall health as measured by PGIC (OR=2.16, p=0.118). TSS reductions were further examined in pts grouped by baseline platelet count. Improvement in EQ-5D-5L OHS was marginally associated with TSS reductions in pts with platelets <50,000/μL (OR=6.03, p=0.057). For pts with platelets <100,000/μL, reductions in TSS were significantly associated with reductions in splenomegaly (SLR ≥50%; OR=9.53, p=0.004), and improvements in the QLQ-C30 GHS/QoL domain (OR=4.03, p=0.022) as well as the EQ-5D-5L OHS (OR=5.49, p=0.008). A significant association between TSS reductions and SVR ≥35% was observed in pts with platelets ≥100,000/μL (OR=3.99, p=0.005). In all pts, improvements in Fatigue as measured by QLQ-C30 were significantly associated with TSS reductions (OR=2.20, p=0.019) as well as in pts with baseline platelets <50,000/μL (OR=17.88, p=0.008) and <100,000/μL (OR=10.18, p<0.001). Conclusions: In the total pt population, TSS reduction was associated with improvements in spleen response and perceived overall health. This trend was also observed in pts with low baseline platelet counts. Additionally, TSS reduction was significantly associated with improvements in fatigue, a major contributor to poor HRQoL in pts with MF. This reinforces the clinical relevance of measuring TSS using a validated instrument as an endpoint in MF trials. Disclosures Mesa: NS Pharma: Research Funding; Pfizer: Research Funding; Gilead: Research Funding; Incyte Corporation: Research Funding; CTI Biopharma: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Genentech: Research Funding; Promedior: Research Funding. Off Label Use: This abstract discusses off-label use of pacritinib. Harrison:Shire: Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Gilead: Honoraria; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau. Cervantes:Novartis: Consultancy, Speakers Bureau; Sanofi-Aventis: Consultancy; CTI-Baxter: Consultancy, Speakers Bureau. Dean:CTI Biopharma: Employment, Equity Ownership. Wang:CTI Biopharma: Employment, Equity Ownership. Yang:Baxalta: Employment, Other: Stock. Vannucchi:Shire: Speakers Bureau; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Compliance with patient-reported outcome assessment in glioma patients: predictors for drop out

2017 ◽  
Vol 5 (2) ◽  
pp. 129-138 ◽  
Author(s):  
Mirjam Renovanz ◽  
Marlene Hechtner ◽  
Karoline Kohlmann ◽  
Mareile Janko ◽  
Minou Nadji-Ohl ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Patient Reported Outcome Measures ◽  
Patient Reported Outcome ◽  
Motor Dysfunction ◽  
Drop Out ◽  
Patient Reported ◽  
Eortc Qlq C30 ◽  
Eortc Qlq

Abstract Background Patient-reported outcomes are of high importance in clinical neuro-oncology. However, assessment is still suboptimal. We aimed at exploring factors associated with the probability for a) drop out of study and b) death during follow-up. Methods Patients were assessed twice during follow-up visits scheduled within 3 to 5 months of each other by using 3 validated patient-reported outcome measures (t1: first assessment, t2: second assessment). As “death” was seen as a competing risk for drop out, univariate competing risk Cox regression models were applied to explore factors associated with dropping out (age, gender, WHO grade, living situation, recurrent surgery, Karnofsky Performance Status, time since diagnosis, and patient-reported outcomes assessed by Distress Thermometer, EORTC-QLQ-C30, EORTC-QLQ-BN20, and SCNS-SF-34G). Results Two hundred forty-six patients were eligible, 173 (70%) participated. Patients declining participation were diagnosed with glioblastomas more often than with other gliomas (56% vs 39%). At t2, 32 (18%) patients dropped out, n = 14 death-related, n = 18 for other reasons. Motor dysfunction (EORTC-QLQ-BN20) was associated with higher risk for non-death-related drop out (HR: 1.02; 95% CI, 1.00–1.03; P = .03). Death-related drop out was associated with age (HR: 1.09; 95% CI, 1.03–1.14; P = .002), Karnofsky Performance Status (HR: 0.92; 95% CI, 0.88–0.96; P < .001), lower physical functioning (EORTC-QLQ-C30; HR: 0.98; 95% CI, 0.96–1.00; P = .04) and lower motor functioning (EORTC-QLQ-BN20; HR: 1.020; 95% CI, 1.00–1.04; P = .02). Conclusion Patients with motor dysfunction and poorer clinical condition seem to be more likely to drop out of studies applying patient-reported outcome measures. This should be taken into account when planning studies assessing glioma patients and for interpretation of results of patient-reported outcome assessments in clinical routine.

Changes in Quality of Life and Disease-Related Symptoms in Patients with Polycythemia Vera Receiving Ruxolitinib or Best Available Therapy: RESPONSE Trial Results

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 709-709
Author(s):  
Ruben Mesa ◽  
Srdan Verstovsek ◽  
Jean-Jacques Kiladjian ◽  
Martin Griesshammer ◽  
Tamas Masszi ◽  
...  
Keyword(s):  
Global Health ◽  
Board Of Directors ◽  
Research Funding ◽  
Symptom Burden ◽  
Global Health Status ◽  
Employment Equity ◽  
Advisory Committees ◽  
Eortc Qlq C30 ◽  
Equity Ownership ◽  
Eortc Qlq

Abstract Background : Polycythemia vera (PV) is a myeloproliferative neoplasm driven by JAK/STAT activation and is associated with erythrocytosis and a broad symptom burden that may negatively impact patient quality of life (QoL). Hydroxyurea (HU) is often used as first-line therapy for high-risk patients but may not effectively control or reduce symptom burden. RESPONSE is a phase III trial comparing ruxolitinib (RUX) with best available therapy (BAT) in patients with PV who were intolerant of or resistant to HU according to modified European LeukemiaNet (ELN) criteria. The primary study endpoint (a composite of hematocrit control and ≥35% spleen volume reduction at Week 32) was achieved by 21% of patients in the RUX arm vs 1% in the BAT arm (P<0.0001); 77% of patients in the RUX arm achieved at least one component of the primary endpoint. The current analysis was conducted to evaluate the effect of RUX on PV-related symptoms and QoL measures in the RESPONSE trial. Methods : Patients with PV aged ≥18 years, resistant to or intolerant of HU (modified ELN criteria) with splenomegaly, and who required phlebotomy for hematocrit control were randomized 1:1 to receive open-label RUX 10 mg twice daily (BID) or BAT (administered based on investigator judgment). Dose adjustments were permitted (RUX, 5-mg BID increments [25 mg BID max]; BAT was adjusted per investigator judgment). Objectives of this analysis included assessment of improvement in symptom burden as assessed by patient-reported outcomes using the 14-item modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and the Patient Global Impression of Change. The 14-item MPN-SAF (graded from 0 [absent] to 10 [worst imaginable]) comprised symptoms related to cytokines (tiredness, itching, muscle ache, night sweats, and sweats while awake), hyperviscosity (vision problems, dizziness, concentration problems, headache, numbness/tingling, ringing in ears, and skin redness), and splenomegaly (abdominal discomfort and early satiety). Changes in total symptom score (TSS; maximum score = 140) and individual symptom scores from baseline to Week 32 were summarized by treatment group. For the EORTC QLQ-C30 Global Health Status/QOL score, the percentage of patients with a minimally important difference (MID) from baseline (10-point change) at Week 32 was summarized. Results : Overall, 222 patients were randomized (RUX, 110; BAT, 112). Median age (range) was similar between arms (RUX, 62.0 [34.0–90.0]; BAT, 60.0 [33.0–84.0]); the RUX and BAT arms were 60% and 71% male, respectively. At Week 32, a higher proportion of patients in the RUX vs the BAT arms had a ≥50% improvement in MPN-SAF TSS (49% vs 5%, respectively) and MPN-SAF symptom cluster scores (cytokine, 64% vs 11%; hyperviscosity, 37% vs 13%; splenomegaly, 62% vs 17%). Median percentage changes in individual symptom scores are presented in the Table. Mean changes from baseline at Week 32 on the 5 items of the PSIS indicated that the severity of pruritus and its interference on daily life improved with RUX (range, −1.5 to −2.2) and was unchanged/worsened with BAT (range, −0.1 to 0.3). Treatment with RUX vs BAT was associated with improved mean changes from baseline at Week 32 on EORTC QLQ-C30 symptom subscales, functional subscales, and Global Health Status/QOL (Table); 46% of RUX patients versus 10% of BAT patients achieved an MID in Global Health Status/QOL (Figure). At Week 32, RUX patients were more likely to rate their global impression of symptom changes as “very much improved” or “much improved” (67%) vs BAT patients (13%). Conclusion : In patients with PV who were resistant to or intolerant of HU, treatment with RUX was associated with greater and clinically meaningful improvements in PV-related symptom burden and QoL measures compared with BAT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Mesa: Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Off Label Use: Ruxolitinib is a JAK1/JAK2 inhibitor approved for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Verstovsek:Incyte Corporation: Research Funding. Kiladjian:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Masszi:Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Durrant:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. He:Incyte Corporation: Employment, Equity Ownership. Jones:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Li:Novartis Pharmaceuticals: Employment, Equity Ownership. Côté:Novartis Pharmaceuticals: Employment, Equity Ownership. Habr:Novartis Pharmaceuticals: Employment, Equity Ownership. Vannucchi:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals First Results from a Nationwide Prospective Non-Interventional Study of Venetoclax-Based 1st Line Therapies in Patients with Acute Myeloid Leukemia (AML) - Revive Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Ofir Wolach ◽  
Itai Levi ◽  
Jonathan Canaani ◽  
Tamar Tadmor ◽  
Sigal Tavor ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Performance Status ◽  
Hypomethylating Agents ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Related Factors ◽  
Real World Setting

Background: The outcome of elderly patients with Acute Myeloid Leukemia (AML) is poor and treatment options in these high-risk groups are limited. Recently, venetoclax combinations with hypomethylating agents or low dose cytarabine were approved to treat patients with AML ineligible for intensive chemotherapy. However limited prospective data is available on the safety and efficacy of venetoclax treatment in routine clinical practice. Israel is among the first countries to have approved venetoclax-based combinations as first line therapy for AML and this treatment is fully reimbursed via the national health system. Here we present the initial results of a prospective, multicenter, nationwide trial that sought to assess the use of venetoclax-based therapy in a real-world setting. Methods: A prospective observational nationwide multicenter trial. Newly diagnosed patients with AML were enrolled at the time of venetoclax-based therapy initiation. Demographic, clinical and patient-related baseline characteristics were documented. Treatment patterns, safety and efficacy outcomes are reported. Patient related outcomes were assessed at baseline and after cycle 3 using the EQ-5D-5L and EORTC QLQ-C30 questionnaires. Results: A total of 70 patients were enrolled between August 2019 and June 2020 (data cut off) with a median age of 75 years (range 45-88) and a median follow-up of 74 days (8-232). Two-thirds of patients were males (62.9%). Over one-quarter (28.6%) of patients had an ECOG performance status of 2 or higher; the median modified Charlson Comorbidity Index (CCI) was 0 (range 1-4) with 27.1% with a CCI ≥2. De-novo AML was documented in 44.3%, secondary AML was diagnosed in 52.8% (secondary to MDS (27.1%), MPNs (11.4%) and therapy related AML (14.3%)). European LeukemiaNet (ELN) risk category was favorable, intermediate and adverse in 8.6%, 30% and 42.9%, respectively (Table 1). Time from diagnosis to initiation of therapy was 8 days (median, range 1-38). The main reasons for choosing venetoclax-based low intensity therapy as reported by treating physicians were patient related factors (mainly age&gt;75 years, performance status) in the majority of cases and adverse disease biology predicting poor response to intensive chemotherapy in 17.1%. Of the 57 patients with available data, 38 (67%) initiated therapy in an inpatient setting with a median hospitalization duration of 12 days (range 1-62 days) and 19 (33%) patients started therapy as outpatients. By data cutoff, of 63 patients that initiated therapy 45, 23 and 7 patients completed cycle 1, cycle 3 and cycle 6 assessments, respectively. Complete remission (CR) or CR with incomplete count recovery (CRi) was achieved in 23/44 (52.3%) patients that were assessed for best response. Of responding patients, 6 (23%, 5 CRi and 1 Partial Remission (PR)) went on to receive an allogeneic transplantation (median age 70.5 years). Ninety percent of patients received venetoclax in combination with hypomethylating agents (azacytidine n=56, decitabine n=1). The full dose of 400mg was administered in 87% of cases with a median ramp-up duration of 3 days. Dose interruptions, dose modifications and dose discontinuations during follow-up were frequent and occurred in 41%, 35% and 27%, respectively. During therapy 63.5% of patients experienced adverse events (AE) of any grade; severe AE's were recorded in 41.3% of patients. Febrile neutropenia was documented in 22.2% and Tumor Lysis Syndrome (TLS) was documented in 2 patients (grade 2; 3.2%). Early death rates at 30 and 60 days were 6.3% and 11.1%, respectively. Conclusion: In the real-world setting venetoclax-based therapies are effective and associated with manageable toxicity including in the outpatient setting. In routine practice patient-related factors and disease-related factors (disease-risk) both seem to play a role in choice of therapy. Venetoclax treatment in real-life practice in Israel appears to follow general recommendations, is tolerable with approximately 90% of patients achieving target dose. These observational data are expected to provide information on patient selection patterns, efficacy and safety and patient related outcomes in patients not in clinical trial. Table Disclosures Wolach: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures and Consultancy, Research Funding; Astellas: Consultancy, Honoraria, Other: Fees for lectures and Consultancy; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Fees for lectures and Consultancy; Amgen: Other: Fees for lectures and Consultancy; Janssen: Other: Fees for lectures and Consultancy. Levi:Abbvie Inc: Consultancy, Research Funding. Canaani:Abbvie: Consultancy, Honoraria, Research Funding. Tadmor:AbbVie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Medison: Consultancy, Speakers Bureau; Neopharm: Consultancy, Speakers Bureau; 6. Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Consultancy, Speakers Bureau. Tavor:Abbvie: Consultancy, Honoraria, Research Funding. Hellmann:Abbvie: Research Funding. Stemer:Abbvie: Research Funding. Cohen:Abbvie Inc: Current Employment, Current equity holder in publicly-traded company. Afik:Abbvie Inc: Current equity holder in publicly-traded company. Ofek:Abbvie Inc: Current Employment. Banayan:Abbvie Inc: Current Employment, Current equity holder in publicly-traded company. Kan:Abbvie Inc: Current Employment, Current equity holder in publicly-traded company. Grunspan:Abbvie Inc: Current Employment, Current equity holder in publicly-traded company. Ofran:AbbVie: Membership on an entity's Board of Directors or advisory committees. Moshe:Astellas: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding.

scholarly journals Survival after Hematopoietic Stem Cell Transplantation in an Older, Fit Cohort of Patients with Advanced Myelodysplastic Syndromes: The MDS-TAO Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 972-972
Author(s):  
Gregory A. Abel ◽  
Haesook T. Kim ◽  
David P. Steensma ◽  
Richard M. Stone ◽  
Angel M. Cronin ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Performance Status ◽  
Time Dependent ◽  
Ecog Performance Status ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Kaplan Meier ◽  
Baseline Characteristics

Abstract Background: The utility of reduced-intensity conditioning hematopoietic stem cell transplantation (RIC HSCT) for fit elderly patients with advanced myelodysplastic syndromes (MDS) is unclear. Methods: The MDS Transplant-Associated Outcomes Study, or "MDS-TAO," was a prospective longitudinal observational study at the Dana-Farber/Harvard Cancer Center designed to examine survival, quality of life, and other outcomes for RIC HSCT versus non-HSCT approaches for HSCT-eligible patients with advanced MDS ages 60 to 75. All patients who met eligibility criteria were approached in the leukemia or HSCT clinics; 96% agreed to enroll. Inclusion criteria included histologically-confirmed diagnosis of MDS or CMML, and (1) therapy-related disease or (2) Int-2/high IPSS (Greenberg, Blood, 1997), or (3) non-IPSS poor-risk cytogenetics (Haase, Blood, 2007), or (4) severe cytopenia/platelet or red cell transfusion-dependence. Exclusions were (1) comorbidities that in the judgment of the treating physician precluded HSCT eligibility (2) prior donor search and (3) patient unwillingness to consider HSCT. Considering time to transplant as a time-dependent variable, hazard ratio for ultimate HSCT was estimated using Cox regression analysis controlling for age, gender, ECOG performance status, IPSS, IPSS cytogenetic risk group, and year of consent. Landmark analyses at 5 months were conducted to present estimates of overall survival for patients who were alive for at least 5 months and received HSCT versus patients who did not (landmark cohort). Subgroup analyses (e.g., molecular characteristics) are also ongoing. Results: 290 patients were enrolled between May 2011 and May 2018; 24 had less than 1.5 months of follow up after consent and were excluded from this analysis. Of the remaining 266 patients, 143 were deceased at last follow up. Baseline characteristics are presented in the table. The median follow-up time among survivors was 31 months (range 1.9, 84). 102 patients received HSCT, of whom 45 subsequently died; of the 164 patients who have not undergone HSCT, 98 have died. The median time to HSCT among those transplanted (n=102) was 4.6 months. The median follow-up for patients alive and not yet transplanted (n=66) was 24 months (range 1.9, 82). Considering time to HSCT as a time-dependent variable (n=266), the hazard ratio for death in multivariable analysis was 0.63 (95% CI 0.42-0.96, p=0.03). Poor risk IPSS cytogenetic group was the only other factor associated with mortality, HR=1.86 (95% CI 1.15-3.00, p=0.006); age, gender, ECOG performance status, IPSS, and consent year were not. Five months was chosen for the landmark analysis given it was closest to the median time to HSCT. In the landmark cohort (N=229), HSCT patients were more likely to have Int-2/high IPSS at baseline (65% vs 35% for none, p=0.0003). No other baseline characteristics were different. Figure A shows Kaplan-Meier plots for the landmark cohort, comparing 54 who received HSCT ≤ 5 months versus 175 patients who did not receive a transplant within 5 months (log rank p=0.04). Figure B shows Kaplan-Meier plots for HSCT comparing 99 patients who received HSCT at any time during follow-up versus 130 patients who did not (log rank p=0.005). Conclusion: In this large cohort of fit elderly patients with advanced MDS, a treatment strategy that included HSCT was associated with better overall survival. Table Table. Disclosures Ho: Jazz Pharmaceuticals: Consultancy. DeAngelo:Incyte: Consultancy, Honoraria; Glycomimetics: Research Funding; Amgen: Consultancy; ARIAD: Consultancy, Research Funding; Blueprint Medicines: Honoraria, Research Funding; Amgen: Consultancy; Shire: Honoraria; Takeda: Honoraria; BMS: Consultancy; Blueprint Medicines: Honoraria, Research Funding; Incyte: Consultancy, Honoraria; Glycomimetics: Research Funding; ARIAD: Consultancy, Research Funding; Pfizer Inc: Consultancy, Honoraria; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria; BMS: Consultancy. Antin:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Soiffer:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Pretreatment Health-Related Quality of Life Profile According to the EORTC QLQ-C30 in Patients with Myelodysplastic Syndromes (MDS): Analysis on 443 Lower-Risk MDS Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2293-2293 ◽  
Author(s):  
Fabio Efficace ◽  
Pasquale Niscola ◽  
Andrea Patriarca ◽  
Francesco Cottone ◽  
Giuseppe A. Palumbo ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Risk Score ◽  
Lower Risk ◽  
Research Funding ◽  
Advisory Board ◽  
Advisory Committees ◽  
Related Quality ◽  
Eortc Qlq C30 ◽  
Health Related ◽  
Eortc Qlq

Abstract Background: Understanding health-related quality of life (HRQOL) profile, including functional aspects and symptom burden, of yet untreated patients with myelodysplastic syndromes (MDS) is important to help clinicians to better identify subgroup of patients in need of special attention from the very beginning of therapy. Aims: The primary objective of this study was to investigate baseline (i.e., pretreatment) HRQOL profile of untreated patients with lower-risk MDS, examining differences by age, gender, risk score category and comorbidity. A secondary objective was to provide age and sex baseline reference HRQOL values, according to the EORTC QLQ-C30 questionnaire, to be used as benchmark comparisons in future MDS studies. Methods: This analysis is based on 443 newly diagnosed adult MDS patients with International Prognostic Scoring System (IPSS) risk score of low (46 %) or intermediate-1 (54%), enrolled in an international prospective cohort observational study. Median age was 75 years (range 32-94), with 261 men (59%) and 182 (41%) women. HRQOL was assessed by the EORTC QLQ-C30 questionnaire at study entry, before any treatment (except for transfusions). This well validated questionnaire consists of five functioning scales: physical, role, emotional, cognitive and social; three symptom scales: fatigue, nausea/ vomiting and pain; six single item scales: dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact; and the global health status/HRQOL scale. The items were scaled and scored using the recommended EORTC procedures. At the time of baseline HRQOL assessment, 111 (25%) patients had received at least one red blood cell transfusion. We used Wilcoxon-Mann-Whitney and Kruskal-Wallis tests for all comparisons. We used the false discovery rate approach to account for multiple testing, with a nominal α-level=0.05. In addition to statistical significance, clinically relevant HRQOL differences were also evaluated based on previously published criteria (Cocks K, et al, J Clin Oncol 29:89-96, 2011). Results: There were not statistically significant differences in any of the HRQOL scales measured by the EORTC QLQ-C30, by the specific IPSS risk category (i.e., low risk vs intermediate-1 risk score). Overall, women reported worse HRQOL scores than men, with clinically relevant differences for physical (Δ=-7.1, P=0.002), role (Δ=-9.9, P=0.002) and emotional functioning, (Δ=-10, P<0.001), nausea/vomiting (Δ=3.7, P<0.001), insomnia (Δ=7.6, P=0.011) and appetite loss (Δ=5.6, P=0.019). Younger patients also reported better outcomes than older patients and this was more evident in the Physical Functioning domain. Also, HRQOL profile varied substantially by number of comorbidities (zero, one, two or more). In general, there was a worsening HRQOL trend with the increase of comorbidities. However, HRQOL impairments were markedly larger in patients with at least two comorbidities, who showed both small and medium clinically relevant differences, when compared to patients with no comorbidities. The largest differences between patients with no comorbidity and those with two or more were found in the following HRQOL domains: Physical Functioning (Δ=-15.3, P<0.001), Fatigue (Δ=-11.9, P<0.001) and Global health status/QOL (Δ=10.0, P<0.001). Full baseline reference values by specific age group categories and sex, according to the EORTC QLQ-C30, are reported in Table 1. Conclusion: Pretreatment HRQOL profile in lower-risk MDS patients vary substantially by age group categories, sex and number of comorbidities, and these differences should be highly considered at the time of treatment start. As in MDS research, the EORTC QLQ-C30 is currently one of the most frequently used HRQOL measure, our baseline reference values provide benchmark data against which other MDS studies using this questionnaire may be compared. Disclosures Efficace: Bristol Meyers Squibb: Consultancy; Seattle Genetics: Consultancy; Orsenix: Consultancy; Incyte: Consultancy; TEVA: Research Funding; TEVA: Consultancy; Lundbeck: Research Funding; Amgen: Consultancy; AMGEN: Research Funding. Palumbo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Platzbecker:Celgene: Research Funding. Stauder:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Breccia:Novartis: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Voso:Celgene: Research Funding, Speakers Bureau. Santini:AbbVie: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy; Novartis: Honoraria. Lubbert:Teva: Other: Study drug; Celgene: Other: Travel Grant; Janssen: Honoraria, Research Funding. Cuneo:Gilead: Other: advisory board, Speakers Bureau; Abbvie: Other: advisory board, Speakers Bureau; Roche: Other: advisory board, Speakers Bureau; janssen: Other: advisory board, Speakers Bureau.

Oxidative Stress and Intravascular Hemolysis in Paroxysmal Nocturnal Hemoglobinuria

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4017-4017
Author(s):  
Makiko Osato ◽  
Jun-ichi Nishimura ◽  
Yukari Motoki ◽  
Satoru Hayashi ◽  
Yasutaka Ueda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Board Of Directors ◽  
Research Funding ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Japanese Patients ◽  
Healthy Individuals ◽  
Intravascular Hemolysis ◽  
Advisory Committees ◽  
Eortc Qlq C30 ◽  
Eortc Qlq

Abstract Background Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal stem cell disorder, characterized by the complement-mediated intravascular hemolysis. Eculizumab is a humanized monoclonal antibody that binds to the human C5 protein, thereby inhibiting terminal complement-mediated hemolysis. PNH patients treated with eculizumab responded with a significant reduction in hemolysis and improved in quality of life (QOL). Recent report shows that PNH-type cells were under the oxidative stress due to elevated levels of intracellular reactive oxygen species (ROS) and/or decreased antioxidant status. Fermented papaya preparation (FPP), a dietary nutriceutical derived from carica papaya, has been shown to modulate oxidative stress damage parameters in vitro and in vivo. To clarify the pathogenetic link between oxidative stress and hemolysis in PNH, the effects of each inhibitor, eculizumab and FPP, in Japanese patients with PNH were investigated independently. Methods Peripheral blood and sera were obtained from patients with PNH and healthy individuals after the obtaining informed consent. The study protocol was approved by the IRB at Osaka University Graduate School of Medicine. For ROS assay, RBCs were measured using 2’-7’-dichlorofluorescin-diacetate. The oxidative stress index (OSI) was derived from the percent ratio of the Reactive Oxygen Metabolites-derived compounds test (Diacron) and the Biological Antioxidant Potential test (Diacron) using a JCA-BM1650 analyzer (JEOL). LDH, biomarker of hemolysis, was measured by routine tests. Eculizumab was administrated according to standard schedule. FPP was taken orally 18g/day for 3 month. Health-related fatigue and QOL were also assessed using the FACIT-fatigue (Version 4A) and EORTC QLQ-C30 (Version 3) instruments. Results PNH patients without eculizumab treatment (pts w/o ecu) showed significantly higher levels in ROS compered to healthy individuals ([mean±SD] 1.13±0.18 vs. 0.84±0.10, p=0.004, n=8). Among these patients, CD59-negative RBCs showed a significant increase in ROS compared to GPI-positive RBCs in corresponding patients (1.23±0.26 vs. 1.13±0.27, p=0.03, n=6). Similarly, the OSI level was significantly higher in pts w/o ecu than healthy individuals (1.32±0.37 vs. 0.97±0.10, p=0.022, n=9) and oxidation activity in sera was significantly higher in pts w/o ecu than healthy volunteers (361.6±91.5 vs. 285.0±31.8, p=0.039, n=9), while antioxidant activity in sera was not significantly different between these 2 groups ([2440.6±191.5 vs. 2601.5±186.6, p=0.09, n=9). Interestingly, there was no significant difference in OSI level between PNH patients on eculizumab (n=8) and healthy individuals (0.84±0.10 vs. 1.07±0.45, p=0.55). Two patients who newly started eculizumab treatment showed improvement in LDH along with ROS generation ([LDH(IU/l)] Pt.I:6082-906, Pt.II:618-211; [ROS] Pt.I:1.57-1.06, Pt.II:1.50-1.40). FPP treatment (n=2) showed little effect on LDH, while it decreased ROS (Pt.I:1.72-1.47, Pt.II:1.16-1.04) and improved the scores in FACIT-fatigue and EORTC QLQ-C30. In addition, those 2 patients showed increase in ROS after discontinuation of FPP (Pt.I:1.47-2.04, Pt.II:1.04-1.19). Conclusion The RBCs and sera derived from Japanese patients with PNH were highly susceptible to oxidative stress compared to healthy individuals. Eculizumab was effective in controlling the oxidative stress, in addition to the hemolysis, suggesting that elevated oxidative stress in PNH was mainly due to the complement-mediated hemolysis. Since FPP showed little effect on hemolysis but had a potential to ameliorate the oxidative stress and improved QOL, FPP could alleviate symptoms associated with oxidative stress and may contribute to the therapeutic option for supportive therapy in PNH. Disclosures Osato: Alexion Pharma: Research Funding. Nishimura:Alexion Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Hayashi:Alexion Pharma: Research Funding. Ueda:Alexion Pharma: Research Funding. Kanakura:Alexion Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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