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2321 The Association of Anemia and Patient Reported Outcomes in the New Era of PNH Treatment

Program: Oral and Poster Abstracts
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
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Esther Natalie Oliva, MD1, Antonio M Risitano, MD, PhD2, Eros Di Bona, MD3*, Alessandro Maria Vannucchi4, Ilaria Maria Delfino1*, Antonio De Vivo, MD5*, Valentina Giai, MD, PhD6*, Rosario Notaro, MD4*, Giuseppe Ianni'7*, Eloise Beggiato, MD8*, Simona Sica, MD, PhD9*, Gaetano La Barba, MD10*, Sneha Balakrishnan11*, Tanuja Thavarajah11*, Simona Raso, MD12*, Raffaele Fontana, MD13*, Wilma Barcellini, MD14*, Bruno Fattizzo, MD14, Roochi Trikha11*, Luana Marano, MD2*, Jens Panse, MD15 and Austin G. Kulasekararaj, MD, MBBS, FRCPath, MRCP11,16,17

1Hematology Unit, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio Calabria, Italy
2Hematology and BMT Unit, AORN San Giuseppe Moscati, Avellino, Italy
3UOC Oncoematologia, AULSS7 Pedemontana, Bassano del Grappa (VI), Vicenza, Italy
4SOD Ematologia, Azienda Ospedaliera Universitaria Careggi di Firenze, Firenze, Italy
5Institute Of Hematology, Bologna, Italy
6Hematology, AOU Città della Salute e della Scienza di Torino, Turin, Italy
7Dielnet SRL, CRO, Reggio Calabria, Italy
8Hematology, AOU Città della Salute e della Scienza di Torino-Presidio Ospedaliero Molinette, Turin, Italy
9Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Italy
10Department of Medicine and Aging Sciences, University of Chieti-Pescara, Italy, Pescara, Italy
11King's College Hospital NHS Foundation Trust, London, United Kingdom
12Department of Hematology and Rare Diseases, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
13Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy
14S.C. Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
15Center of Integrated Oncology (CIO), Aachen, Bonne, Cologne, Düsseldorf (ABCD), Germany
16National Institute for Health Research and Wellcome King's Clinical Research Facility, London, United Kingdom
17King's College Hospital, London, United Kingdom

Background: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder characterized by hemolytic anemia and possibly complicated with thromboembolism and other cytopenias. Symptoms such as fatigue and dyspnea have been attributed to intravascular hemolysis rather than to the extent of anemia. Anti-complement treatment in symptomatic hemolytic PNH patients is associated with improved survival and quality of life (QoL). To date, cancer-specific patient-reported outcome measures (PROMS), such as EORTC QLQ-C30, have been used in PNH patients, with fatigue being identified as a major PRO issue. However, many other impacts of PNH are unassessed by the cancer PROM. A novel PNH-specific PROM, QLQ-AA/PNH, consisting of 54 items, is undergoing validation. In this observational multicenter international study, the primary endpoint is to evaluate differences in EORTC QLQ-C30 scores between patients without versus those with intravascular hemolysis and, as a secondary endpoint, the same differences in QLQ-AA/PNH scores. Other secondary endpoints include reliability and intraclass correlation by test-retest methodology of QLQ-AA/PNH and factors associated with QoL and symptoms.

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.

*signifies non-member of ASH