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4355 Dosing Pattern of Ruxolitinib (RUX) in Patients with Myelofibrosis (MF) in Italy: Results from a Prospective Observational Study (ROMEI)

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
adult, Clinical Practice (Health Services and Quality), MPN, Chronic Myeloid Malignancies, Diseases, Therapies, Myeloid Malignancies, Study Population, Human
Monday, December 12, 2022, 6:00 PM-8:00 PM

Massimo Breccia, MD1*, Paola Guglielmelli, MD, PhD2, Francesco Mendicino3*, Alessandra Malato, MD4*, Giuseppe A. Palumbo5*, Carmine Selleri6, Daniela Cilloni, MD7*, Patrizio Mazza, MD8*, Sergio Siragusa, MD9, Elisabetta Abruzzese, MD10, Maurizio Martelli11*, Giulia Benevolo, MD12*, Erminia Rinaldi13*, Monica Crugnola, MD14*, Serena Rupoli, MD15*, Vincenzo Pavone16*, Massimiliano Bonifacio, MD17*, Fabrizio Pane, MD18, Giuseppe Carli19*, Maria Langella20*, Marta Bruno Ventre21*, Elena Maria Elli, MD22*, Stefana Impera, MD23*, Anna Marina Liberati24, Nicola Di Renzo, MD25*, Bruno Martino26*, Paolo Sportoletti, MD27*, Mario Tiribelli, MD28*, Gianni Binotto, MD29*, Mario Annunziata30*, Mauro Di Ianni31*, Giorgio La Nasa32*, Antonietta Pia Falcone33*, Rossana Leanza34*, Antonio Volpe35*, Filippo Gherlinzoni36*, Valerio De Stefano, MD37*, Daniele Vallisa38, Sabrina Leonetti Crescenzi, MD39*, Francesco Cavazzini, MD40*, Alessandra Ricco, MD41*, Carmela Barberio42*, Alessandra Misto42*, Francesco Passamonti, MD43* and Francesca Palandri, PhD, MD44*

1Division of Hematology, Department of Translational and Precision Medicine, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
2CRIMM, Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
3U.O.C. di Ematologia, Azienda Ospedaliera "Annunziata", Cosenza, Italy
4UOC di Oncoematologia Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
5Dipartimento di Scienze Mediche Chirurgiche e Tecnologie Avanzate "G.F. Ingrassia", Unità Operativa di Ematologia con TMO AOU "Policlinico - San Marco", Università degli Studi di Catania, Catania, Italy
6UOC di Ematologia e Trapianti di Cellule Staminali Emopoietiche, Dipartimento di Medicina, Università di Salerno, AOU San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy
7Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
8Dept. of Hematology-Oncology, Ospedale Moscati, Taranto, Italy
9UOC di Ematologia, Azienda Ospedaliero-Universitaria Policlinico “P. Giaccone”, Palermo, Italy
10Hematology, S. Eugenio Hospital, Tor Vergata University, ASL Roma2, Rome, Italy
11Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
12Ematologia U, A.O.U. Città della Salute e della Scienza, Turin, Italy
13Hematology, A. Perrino Hospital, Brindisi, Italy
14Hematology and BMT Center, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
15Clinic of Hematology, Ospedali Riuniti di Ancona, Ancona, Italy
16Department of Haematology and Bone Marrow Transplantation, “Card. G. Panico” Hospital, Tricase, Italy, Tricase, Italy
17Department of Medicine, Section of Hematology, University of Verona and Azienda Ospedaliera Universitaria Integrata, Verona, Italy
18Division of Hematology and Bone Marrow Transplantation, Department of Medicine and Surgery University of Naples Federico II, Napoli, Italy
19U.O.C. Ematologia Ospedale san Bortolo, Vicenza, Italy
20U.O. Oncoematologia, Presidio Ospedaliero Andrea Tortora - ASL Salerno, Salerno, Italy
21Divisione di Oncologia, ASST Fatebenefratelli Sacco, Milano, Italy
22Divisione di Ematologia adulti e Unità trapianto di midollo ASST Monza Azienda Ospedaliera San Gerardo, Monza, Italy
23UOC Ematologia, Dipartimento Oncologico- ARNAS Garibaldi, Catania, Italy
24Oncoematologia , AO S Maria di Terni - Università degli Studi di Perugia, Perugia, Italy
25U.O. Ematologia, Presidio Ospedaliero Vito Fazzi ASL, Lecce, Italy
26Hematology Unit, Department of Hemato-Oncology and Radiotherapy,Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy
27Section of Hematology, Department of Medicine and Surgery, Center for Hemato-Oncological Research (CREO), University of Perugia, Perugia, Italy
28Clinica Ematologica, Az.Osped.-Universit.Santa Maria della Misericordia di Udine, Udine, Italy
29Hematology and Clinical Immunology Unit, Department of Medicine, Padua University Hospital, Padova, Italy
30Divisione di Ematologia, Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli, Napoli, Italy
31Department of Medicine and Aging Sciences, University of Chieti-Pescara, Pescara, Italy
32S.C Ematologia e CTMO, A O Brotzu Osp Onc Armando Businco Centro Rif Onc Reg, Cagliari, Italy
33Unità di Ematologia, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
34U.O.C. Ematologia, Az.Ospe.Universitaria Policlinico G. Martino Univ di Messina, Messina, Italy
35Ematologia, Az Ospedaliera SG Moscati, Avellino, Italy
36Unità Operativa Complessa di Ematologia, Pres.Ospedaliero S.Maria di Ca' Foncello, Treviso, Italy
37Sezione di Ematologia, Università Cattolica, Fondazione Policlinico A. Gemelli IRCCS, Roma, Italy
38Ematologia e Centro Trapianti, Dipartimento di Oncologia-Ematologia, Presidio U.Ospedaliero di Piacenza AUSL Piacenza, Piacenza, Italy
39S.C. Ematologia, Azienda Ospedaliera S Giovanni Addolorata, Roma, Italy
40Ematologia, Az Osp Univ Ferrara Arcispedale S Anna Univ. degli Studi Ferrara, Ferrara, Italy
41UOC Ematologia, Az. Osp. Univ Policlinico, Bari, Bari, Italy
42Novartis Farma S.p.A., Origgio, Italy
43Università degli Studi dell'Insubria, Ospedale di Circolo - ASST Sette Laghi, Varese, Italy
44IRCCS Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Bologna, Istituto di Ematologia "Seràgnoli, Bologna, Italy

Introduction

ROMEI (RUX Observational study in Myelofibrosis treated patiEnts in Italy) is a prospective observational study that aims to bridge the knowledge gap between clinical experience of registration trials and routine patient management by following 500 MF patients (pts) treated with RUX in everyday clinical practice. Enrollment started in April 2017 and closed in May 2022, reaching the target. Herein we describe the RUX dosing pattern that emerged during the observation period for the cohort of pts entering this interim analysis.

Methods

An interim analysis was scheduled when all enrolled pts completed the first 12 months of follow-up or prematurely interrupted the study by May 31, 2019.The first visit of the last enrolled patient plus 12 months was established as cut-off date for the analysis.

RUX starting dose overall according to baseline platelet count (<100 x109/L, 100-200 x109/L and >200 x109/L), mean daily dose (mg/day) overall and by initial dose (i.e. 10, 15, 20, 30 or 40 mg/day) were analyzed. Mean daily dose was calculated as cumulative total dose of RUX/ number of treated days in each month (only days in which the patient was effectively treated were considered for the mean daily dose computation). RUX dose changes (number and reasons), interruptions (temporary/permanent and reasons) and time to permanent discontinuation were collected. Patients who withdrew consent from the study or were lost to follow-up were censored at the time of consent withdrawal or last contact date, respectively. Indeed, those still in treatment at the cut-off date for the analysis were censored at the cut-off date.

Results

212 pts took at least one dose of study medication (Safety Set) and were evaluable for this analysis. Table 1 shows the most relevant baseline patient characteristics and initial RUX dose. The mean initial RUX dose was equal to 29.9±10.9 mg/day (range 10-40 mg/day). RUX mean daily dose in the overall period of observation was 25.8±10.3 mg/day (range 5.6-49.5 mg/day), slightly higher in the first month and stable with mild fluctuation over time. According to initial RUX dosage, mean daily dosage seemed to decrease by month in pts starting with 30 and 40 mg/day, slightly increase in those starting with 10 mg/day and quite stable in pts starting at 20 mg/day (Fig 1).

Out of the 212 pts, 168 (79%) had at least one change in RUX dosage, and the mean number of changes was 2.4 ± 2.39 (range 0 – 12). The proportion of pts with at least one change in RUX dosage was slightly higher with the increase of IPSS risk: 69%, 78% and 86% in Intermediate-1 risk, Intermediate-2 risk and High risk, respectively.

Fifty-three temporary interruptions were reported by 39 pts (18%). Most of them were due to adverse events, lab or test abnormality (47, 88.68%). After temporary interruption, most pts restarted RUX at same dosage that they took before interruption (62%) while 30% restarted at a lower dosage and only 7.5% at a higher dosage. The first temporary interruption in these 39 pts was observed at a median time of 57 days (range 7-482) from treatment start and the mean duration of interruptions was 21.1±30.9 days (range 1-210 days). As expected, both temporary and permanent discontinuation were higher in pts with platelets < 100 x109/L.

Fifty-five pts (26%) permanently discontinued RUX, and the main reasons (frequency >10%) were adverse events (18%), stem cell transplantation (16%), death (14.5%), physician’s decision (13%) and lost to follow-up (11%). The 6-month and the 12-month permanent discontinuation rates estimated were 13.3% (95% CI: 9.4, 18.7) and 21.5% (95% CI: 16.6, 27.8), respectively.

Conclusions

RUX dosing pattern emerging from the ROMEI study shows a potential sub-optimal use in clinical practice versus approved indications at the time of data cut-off (May 2019). Approximately 25% of pts in the higher platelet count (>200 x 109/L group) were not assigned to the recommended starting dose (20 mg bid) receiving a lower dosage. Most patients received dose adjustment during treatment while a limited number of patients permanently discontinued RUX, suggesting that dose modulation allows to maintain treatment over time. Additional analysis will elucidate whether the choice of baseline dosage and modulation over treatment might further impact treatment outcome in the short and long term.

Disclosures: Breccia: Novartis, Incyte, Pfizer, BMS, Abbvie: Honoraria. Guglielmelli: Novartis, Abbvie: Other: Other member of advisory board, speaker at meeting. Palumbo: Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Siragusa: Csl Behring, Takeda, Amgen, Novartis, Bayer, Sobi, Novo Nordisk: Honoraria. Abruzzese: BMS, Incyte, Novartis, Pfizer: Consultancy. Benevolo: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Crugnola: Novartis: Speakers Bureau; Amgen: Speakers Bureau. Pane: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte, BMS, Janssen, Amgen, Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Speakers Bureau. Carli: Novartis: Consultancy. Liberati: Takeda: Research Funding; iQVIA: Research Funding; PSI: Research Funding; Verastem: Research Funding; Secura Bio: Research Funding; Sanofi: Research Funding; Roche: Research Funding; Novartis: Research Funding; Morphosys: Research Funding; Janssen: Research Funding; DR REDDY’S LABORATORIES SPA: Research Funding; Celegene: Research Funding; BMS: Research Funding; Beigene: Research Funding; AbbVie: Research Funding; LOXO: Research Funding; MEI-PHARMA: Research Funding; EPZIME: Research Funding. Binotto: Novartis, BMS, Incyte, Pfizer: Honoraria. De Stefano: GlaxoSmithKline: Honoraria, Speakers Bureau; Bristol Myers Squibb/Celgene: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; AbbVie: Honoraria; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Barberio: Novartis: Current Employment. Misto: Novartis: Current Employment. Passamonti: Novartis, Bristol-Myers Squibb/ Celgene, Abbvie, Roche, AOP Orphan.: Speakers Bureau; Novartis, Bristol-Myers Squibb/ Celgene, Sierra Oncology, Abbvie, Roche, AOP Orphan, Karyiopharma, Kyowa Kirin and MEI.: Consultancy. Palandri: Kartos/Telios: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Sierra Oncology: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; CTI: Consultancy, Honoraria; AOP: Consultancy, Honoraria.

*signifies non-member of ASH