Session: 905. Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies: Poster I
Hematology Disease Topics & Pathways:
Research, Adult, Clinical Practice (Health Services and Quality), Bone Marrow Failure Syndromes, Clinical Research, Paroxysmal Nocturnal Hemoglobinuria, Patient-reported outcomes, Diseases, Study Population, Human
Materials and Methods: Patients of age ≥ 18 years with PNH from Italy and UK have been included. Exclusion criteria are active bone marrow failure, history of treatment for cancer within the last 5 years and clinically significant comorbidities that impact PROMs. Patients completed both EORTC QLQ-C30 and QLQ-AA/PNH on the day of the scheduled treatment at the clinic and after 1-2 weeks. Demographics and disease features were collected at baseline. Intravascular hemolysis is defined by serum lactate dehydrogenase (LDH) ≥ 1.5 times upper limit of normal.
Results: From May 13, 2021, and March 12, 2024, 82 PNH patients (male 43, female 39) of mean age 50 (SD 15) years were included. Ongoing treatment consisted of eculizumab (N=24), ravulizumab (N=32), investigational products (N=20), and supplements or other therapy (N=6). At the time of this analysis, thirteen patients (16%) suffered from hemolysis. Mean Hb level was 11.0 (SD 1.7, range 7.9 – 15.4) g/dL. EORTC QLQ-C30 scores were comparable to the normal European and US population. Noteworthy, mean fatigue score by EORTC QLQ-C30 was 27.9 (SD 21.9; normal reference = 29.5, SD 25.5). Cronbach alpha estimates of the QLQ-AA/PNH at the first assessment (t1) and at retest (t2) were above 0.8 for all domains except for the social support (t1=0.26, t2=0.20) and body index (t1=0.26, t2=0.11). The intra-class correlation coefficient for all domains ranged from 0.70 to 0.95. The correlation between the mean score of t1 and t2 by Spearman’s correlation coefficient ranged from 0.45 to 0.92, with QLQ-AA/PNH domains PNH illness intrusiveness, PNH physical functioning, PNH emotional functioning and PNH stigmatisation showing the strongest correlations. Convergent validity with Spearman’s rank correlation test showed high correlations between the following domains of QLQ-AA/PNH: emotional function (EF), cognitive function (CF), physical function (PF) and role function (RF) with the corresponding domains of the EORTC QLQ-C30 [ EF (rs=0.69), CF (rs=0.60), PF (rs=0.72) and RF (rs=0.68); p<0001]. Neither the EORTC QLQ-C30 nor the QLQ-AA/PNH correlated with residual intravascular hemolysis (p=ns). Noteworthy there were significant correlations between Hb levels and all domains of the QLQ-AA/PNH, except for the social support. Between cases had Hb <10 g/dL (N=19) and the remaining cases with higher levels , there were significant differences in almost all domain scores of the EORTC QLQ-C30: PF (78.9 vs 89.6, p=0.005), RF (71.0 vs 89.9, p<0.0001), CF (75.4 vs 89.7 p<0.001), SF (73.7 vs 92.7, p<0.0001)] and in the QLQ-AA/PNH stigmatisation (56.1 vs 84.7, p=0.009), illness intrusiveness (63.7 vs 83.7, p=0.006), infection (66.7 vs 87.1, p=0.002) and other symptoms (76.9 vs 88.2, p=0.009).
Conclusions: In this cohort of patients with PNH with ongoing treatment, PROs were similar to the normal European and USA population. While impaired PRO was not associated with the extent of residual intravascular hemolysis (as LDH), we demonstrate that the degree of anemia (as Hb level) impacts on outcome in several domains, other than fatigue, underscoring the opportunity of switching to resolution of anemia to further improve outcome in affected areas.
Disclosures: Oliva: Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Halia Therapeutics: Patents & Royalties; Sobi: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Grande Ospedale Metropolitano Bianchi Melacrino Morelli: Current Employment; Ryvu: Consultancy, Honoraria, Patents & Royalties; Daiichi Sankyo: Consultancy, Honoraria; Janssen: Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Alexion: Consultancy, Honoraria, Speakers Bureau. Risitano: Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amyndas: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Apellis: Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vannucchi: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Italfarmaco: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; AOP: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees. Giai: Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sobi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Other: All authors received support for third-party writing assistance, furnished by Akshaya Srinivasan, PhD, CMPP, of Nucleus Global, an Inizio company, and funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland.; Incyte: 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. Notaro: Alexion Pharmaceuticals: Other: lecture fees, Investigator Board; Astra Zeneca: Other: lecture fees, Investigator Board; Novartis: Other: Investigator Board; Sobi: Other: Investigator Board. Beggiato: Alexion: Speakers Bureau; Novartis: Speakers Bureau; Sobi: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau. Barcellini: Alexion, AstraZeneca Rare Disease: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi: Consultancy; Novartis: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau. Fattizzo: Sobi: Speakers Bureau; Samsung: Speakers Bureau; Alexion: Consultancy; Novartis: Consultancy; Roche: Consultancy, Other: travel to congress; Janssen: Consultancy; Agios: Research Funding; Zenas BioPharma: Research Funding. Trikha: Alexion AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees; Swedish Orphan Biovitrum AB: 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. Panse: F Hoffmann-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: All authors received support for third-party writing assistance, furnished by Akshaya Srinivasan, PhD, CMPP, of Nucleus Global, an Inizio company, and funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland., Speakers Bureau; Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Current equity holder in publicly-traded company, Honoraria; Bristol Myers Squibb: Consultancy, Current equity holder in publicly-traded company, Honoraria; Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Samsung Bioepis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria; Swedish Orphan Biovitrum AB: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis: Consultancy, Current equity holder in publicly-traded company, Honoraria; Swiss Biopharma: Honoraria; Sanofi: Consultancy, Current equity holder in publicly-traded company; Amgen: Consultancy, Current equity holder in publicly-traded company, Honoraria; Boehringer Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kulasekararaj: Pfizer: Consultancy, Honoraria, Speakers Bureau; Apellis: Consultancy, Honoraria, Speakers Bureau; Samsung: Consultancy, Honoraria, Speakers Bureau; Sobi: Consultancy, Honoraria, Speakers Bureau; Alexion: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Achillion: Consultancy, Honoraria, Speakers Bureau; Akari: Consultancy, Honoraria, Speakers Bureau; Agios: Honoraria; Silence Therapeutics: Honoraria; Novo Nordisk: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy; Ra Pharma: Consultancy, Honoraria, Speakers Bureau; BioCryst: Consultancy, Honoraria, Speakers Bureau.