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2464 Reaction - Real Life Use of Ravulizumab in Italian Patients with Paroxysmal Nocturnal Hemoglobinuria a Multicenter Observational Retrospective and Prospective Cohort Study, Final Results

Program: Oral and Poster Abstracts
Session: 101. Red Cells and Erythropoiesis, Excluding Iron: Poster II
Hematology Disease Topics & Pathways:
Research, Bleeding and Clotting, Adult, Clinical Research, Therapy sequence, Diseases, Thrombotic disorders, Treatment Considerations, Real-world evidence, Study Population, Human
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Bruno Fattizzo, MD1, Anna Paola Iori2*, Antonio De Vivo, MD3*, Elisabetta Metafuni4*, Amalia Figuera, MD5*, Luana Marano, MD6*, Esther Natalie Oliva, MD7*, Maria Bruna Greve8*, Francesco Lanza, MD9*, Eros Di Bona, MD10*, Jacopo Micozzi, MD11*, Giovanni Caocci, MD12, Francesca Fioritoni13*, Fabio Ciceri, MD14*, Angela Amendola15*, Carmine Selleri, MD16, Francesco Longu17*, Alessandra Tucci, MD18, Eloise Beggiato, MD19*, Davide Rapezzi, MD20*, Alessandro Cignetti21*, Tiziana Anna Urbano22*, Nicola Di Renzo23*, Valeria Amico, MD24*, Pierangelo Spedini25*, Alessandro Rambaldi26,27, Simona Raso, MD28*, Cristina Clissa, MD29*, Sergio Cabibbo30*, Barbara Roncari31*, Lucia Simoni31*, Benedetta Campolo32*, Fabio Carini33*, Davide Mattiuzzi33* and Wilma Barcellini, MD34*

1Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
2Department of Translational and Precision Medicine, Policlinico Umberto I Hospital, Sapienza University of Rome, Roma, Roma, ITA
3Institute Of Hematology, Bologna, Italy
4Hematology Unit, Università Cattolica Del Sacro Cuore, Rome, ITA
5Hematology and Bone Marrow Transplatation Unit, A.O.U. Policlinico “G. Rodolico - S.Marco", Catania, 95123, ITA
6Hematology and BMT Unit, AORN San Giuseppe Moscati, Avellino, Italy
7Hematology, Melacrino Morelli Hospital, Reggio Calabria, AL, Italy
8Grande Ospedale Metropolitano di Reggio Calabria - Melacrino Morelli, Reggio Calabria, Italy
9Division of Hematology, Onco-hematologic Department, AUSL della Romagna, Ravenna, Italy
10UOC Oncoematologia, AULSS7 Pedemontana, Bassano del Grappa (VI), Vicenza, Italy
11Division of Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
12University of Cagliari, Monserrato, Italy
13Department of Haematology, Pescara, ITA
14Hematology and Bone Marrow Transplantation Unit, I.R.C.C.S. San Raffaele Scientific Institute, Milan, Italy
15Ematologia, AOR San Carlo, Potenza, Potenza, ITA
16Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy
17University of Sassari, Sassari, Missouri, ITA
18Department of Hematology, ASST Spedali Civili di Brescia, Brescia, Italy
19Hematology, AOU Città della Salute e della Scienza di Torino-Presidio Ospedaliero Molinette, Turin, Italy
20Department of Hematology, S. Croce e Carle Hospital, Cuneo, Italy
21University Division of Hematology and Cell Therapy, A.O. Ordine Mauriziano, Turi, Torino, ITA
22U.O. Ematologia Ospedale “S. Giuseppe Moscati”, Taranto, ASL TA1, Taranto, ITA
23"Vito Fazzi" Hospital, Hematology and Stem Cell Transplant Unit, Lecce, Italy
24Immunoematologia e Trasfusione Azienda Ospedaliera “San Pio”, Benevento, Italy, benevento, Italy
25ASST Cremona, Ematologia, Cremona, ITA
26UO Ematologia, ASST Papa Giovanni XXIII, Bergamo, Italy
27Department of Oncology-Hematology, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
28Department of Hematology and Rare Diseases, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
29Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
30ASP Ragusa- P.O. Giovanni Paolo II Ematologia, Ragusa, Italy
31IQVIA, Milano, Italy
32Alexion AstraZeneca Rare Disease, Milan, ITA
33Alexion Astrazeneca Rare Disease, Milano, Italy
34Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

Title:

REACTION - Real Life Use of Ravulizumab in Italian PatiEnts with PAroxysmal NoCturnal Hemoglobinuria a MulTicenter ObservatIONal Retrospective and Prospective Cohort Study, Final Results

Introduction:

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disorder characterized by uncontrolled terminal complement activation leading to hemolytic anemia, thrombosis, organ damage and premature mortality. In 2021, ravulizumab was approved in Italy as a treatment for PNH, but real-world evidence is currently lacking. The REACTION study (NCT05274633), a multi-center observational cohort study in Italy, aims to assess the effectiveness and tolerability in Italian patients with PNH who have switched to ravulizumab after at least 26 weeks of treatment with eculizumab.

Methods:

The REACTION study is an Italian multi-center, observational study composed of retrospective and prospective periods on the same PNH patients. The study is designed to collect effectiveness data of ravulizumab in patients already treated with eculizumab for at least 26 weeks and who switched to ravulizumab treatment. All patients eligible to start the new drug as per clinical practice were enrolled in participating sites, with the exception of subjects with a history of hematopoietic stem cell transplantation , pregnant or breastfeeding. Patients had to sign informed and privacy consent to be enrolled in the study.

Efficacy and safety data were collected at the following timepoints: -52 weeks, -26 weeks, baseline, 18 weeks, 34 weeks and 52 weeks. Baseline was defined as the day of ravulizumab induction dose.

The primary endpoint was to describe the percentage change in lactate dehydrogenase (LDH) from baseline to the end of observation period during ravulizumab treatment at 52 weeks.

Here we present the final analysis on primary endpoints, breakthrough hemolysis (BTH) event rate and transfusion needs, over a follow-up period of 52 weeks of ravulizumab treatment.

Results:

The full analysis set comprised 80 patients, with a median age of 51.5 years at baseline, of whom 39 (48.8%) were male, enrolled in 28 centers across Italy.

The median time since PNH diagnosis was 9.0 years (IQR: 4.3 – 16.7), most patients had no comorbidities (53 [66.3%]) or PNH symptoms (55 [68.8%]) at baseline. Median duration of eculizumab treatment was 6.1 (2.9 – 10.7) years, median dosage was 900.0 mg and median administration frequency was 14.0 days. Median duration of ravulizumab treatment was 50.0 weeks, median induction dose was 2700.0 mg, median maintenance dose was 3300.0 mg and median administration frequency was 56.0 days.

The primary endpoint showed that the median percentage change in LDH from baseline to the end of the observation period was -2.7%. The median Hgb levels at baseline was 10.8 g/dL and at the end of the observation period was 11.2 g/dL.

The observed rate of BTH events per 100 patients-year decreased from 6.3 during the eculizumab period to 2.6 during the ravulizumab period.

During the eculizumab treatment period, 2 patients experienced a total of 5 BTH events, of which 4 were unrelated to any medical events. During the ravulizumab treatment, 2 patients experienced 2 BTH events, which were related to gastroenteritis and COVID-19 infections.

For transfusion requirements, among the 80 patients, during eculizumab period 20 patients (25.0%) needed 108 packed red blood cells units, while in the ravulizumab period 16 patients (20.0%) needed 67 packed red blood cells units

The RWE analysis did not reveal any new pharmacovigilance signals. No cases of meningococcal infections were reported. Two deaths occurred, due to senescence and to a concomitant newly diagnosed sarcoma, respectively. Both deaths were not related to ravulizumab.

Conclusions:

This is the first presentation of the REACTION study’s final results, that confirm the effectiveness and tolerability of switching patients with PNH from eculizumab to ravulizumab, as emerged from the phase III clinical trials. Ravulizumab effectively maintained control of intravascular hemolysis, as indicated by LDH levels, and sustained stable hemoglobin levels throughout the prospective period. The transfusion need and the total number of BTH events decreased during ravulizumab compared to the eculizumab period. Furthermore, during ravulizumab, both recorded BTH events were related to medical conditions.

Disclosures: Fattizzo: Sobi: Speakers Bureau; Samsung: Speakers Bureau; Novartis: Consultancy; Roche: Consultancy, Other: travel to congress; Alexion: Consultancy; Janssen: Consultancy; Agios: Research Funding; Zenas BioPharma: Research Funding. Ciceri: ExCellThera: Membership on an entity's Board of Directors or advisory committees. Tucci: Abbvie: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Lilly: Membership on an entity's Board of Directors or advisory committees; Regeneron: Membership on an entity's Board of Directors or advisory committees; Kiowa Kyrin: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Beggiato: Alexion: Speakers Bureau; Novartis: Speakers Bureau; Sobi: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau. Rambaldi: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Kite-Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau. Roncari: IQVIA: Current Employment; Alexion: Other: Provided Service to Alexion. Simoni: IQVIA: Current Employment; Alexion: Other: Provided Service to Alexion. Campolo: Alexion: Current Employment. Carini: Alexion: Current Employment. Mattiuzzi: Alexion: Current Employment. Barcellini: Sanofi: Consultancy, Honoraria, Speakers Bureau; 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.

*signifies non-member of ASH