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Observational Study
. 2025 Apr 1;131(7):e35801.
doi: 10.1002/cncr.35801.

Dosing and clinical outcomes of ruxolitinib in patients with myelofibrosis in a real-world setting: Interim results of the Italian observational study (ROMEI)

Massimo Breccia  1 , Francesca Palandri  2 , Maurizio Martelli  3 , Francesco Mendicino  4 , Alessandra Malato  5 , Giuseppe A Palumbo  6 , Silvia Sibilla  7 , Nicola Di Renzo  8 , Elisabetta Abruzzese  9 , Sergio Siragusa  10 , Monica Crugnola  11 , Carmine Selleri  12 , Fabrizio Pane  13 , Paolo Sportoletti  14 , Bruno Martino  15 , Stefana Impera  16 , Alessandra Ricco  17 , Maria Langella  18 , Paolo Ditonno  19 , Giuseppe Carli  20 , Federico Itri  21 , Anna Marina Liberati  22 , Tiziana Urbano  23 , Agostino Tafuri  24 , Vita Polizzi  25 , Domenico Pastore  26 , Erika Morsia  27 , Giulia Benevolo  28 , Giorgia Micucci  29 , Gabriella Farina  30 , Massimiliano Bonifacio  31 , Elena Maria Elli  32 , Angelo Gardellini  33 , Valerio De Stefano  34 , Giovanni Caocci  35 , Antonietta Pia Falcone  36 , Daniele Vallisa  37 , Marco Brociner  38 , Mario Tiribelli  39 , Gianni Binotto  40 , Barbara Pocali  41 , Francesco Cavazzini  42 , Simona Tomassetti  43 , Francesca Lunghi  44 , Mauro Di Ianni  45 , Alessandro Allegra  46 , Barbara Anaclerio  47 , Serena Mazzotta  48 , Nicola Orofino  49 , Filippo Gherlinzoni  50 , Chiara Castiglioni  51 , Marina Landoni  51 , Diletta Valsecchi  51 , Michela Magnoli  52 , Paola Guglielmelli  53 , Francesco Passamonti  54
Affiliations
Observational Study

Dosing and clinical outcomes of ruxolitinib in patients with myelofibrosis in a real-world setting: Interim results of the Italian observational study (ROMEI)

Massimo Breccia et al. Cancer. .

Abstract

Background: Myelofibrosis (MF) significantly impacts patients' overall survival (OS) and quality of life (QOL). This prospective study analyzed ruxolitinib dosing patterns and associated clinical outcomes in patients with MF over 12 months.

Methods: ROMEI, a multicenter, observational, ongoing study, enrolled 508 adult patients with MF treated with ruxolitinib. For the current interim analysis, eligible patients with baseline platelet values were categorized into two groups based on ruxolitinib starting dosage: as expected (AsEx, n = 174) and lower than expected (LtEx, n = 132); ruxolitinib dose changes, interruptions and time to permanent discontinuation were analyzed, along with symptoms response, health-related QOL scores, spleen response, OS, and safety.

Results: Forty-three percent of patients started at a lower-than-expected dose. Both groups showed reduction in average daily ruxolitinib doses over 12 months. Symptoms response rate was similar in both groups at week 48 (40.8% AsEx vs 40.9% LtEx). The AsEx group demonstrated higher spleen response rates at both 24 weeks (50.0% vs 30.2%) and 48 weeks (57.7% vs 45.8%) with a shorter median time to first response (3.3 vs 11.1 months, p = .019) when compared to the LtEx group. Both groups showed upward trends in health-related QOL values. Estimated median OS was not reached for the AsEx group versus 4.7 years in the LtEx group (p = .014). Adverse events were reported in 87.4% and 84.9% of patients in the AsEx and LtEx groups, respectively.

Conclusions: The ROMEI study demonstrated the importance of optimal ruxolitinib dosage in patients with MF for maximum effectiveness and improved OS, with manageable safety.

Keywords: ROMEI study; dosing patterns; lower recommended dose; myelofibrosis; ruxolitinib; spleen response.

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Conflict of interest statement

Massimo Breccia: received honoraria from Novartis, Pfizer, Incyte, BMS/Celgene, AbbVie, AOP, and GSK; Francesca Palandri: consultant and received honoraria from AbbVie, Amgen, AOP, BMS Celgene, Novartis, CTI, GSK, Grifols, Karyopharm, Morphosis, Sierra Oncology, and Sobi; Maurizio Martelli: no conflicts of interest; Francesco Mendicino: no conflicts of interest; Alessandra Malato: no conflicts of interest; Giuseppe A. Palumbo: honoraria for Advisory Boards/Meetings as speaker from Abbvie, AOP Orphan, AstraZeneca, Beigene, Bristol‐Myers Squibb, GSK, Incyte, Morphosys, and Novartis; support for attending meetings and travel from Abbvie, AOP Orphan, Beigene, Johnson & Johnson, Novartis, and Stemline Menarini; Silvia Sibilla: no conflicts of interest; Nicola Di Renzo: no conflicts of interest; Elisabetta Abruzzese: no conflicts of interest; Sergio Siragusa: no conflicts of interest; Monica Crugnola: no conflicts of interest; Carmine Selleri: no conflicts of interest; Fabrizio Pane: no conflicts of interest; Paolo Sportoletti: no conflicts of interest; Bruno Martino: no conflicts of interest; Stefana Impera: no conflicts of interest; Alessandra Ricco: no conflicts of interest; Maria Langella: no conflicts of interest; Paolo Ditonno: no conflicts of interest; Giuseppe Carli: no conflicts of interest; Federico Itri: no conflicts of interest; Anna Marina Liberati: no conflicts of interest; Tiziana Urbano: no conflicts of interest; Agostino Tafuri: no conflicts of interest; Vita Polizzi: no conflicts of interest; Domenico Pastore: no conflicts of interest; Erika Morsia: no conflicts of interest; Giulia Benevolo: no conflicts of interest; Giorgia Micucci: no conflicts of interest; Gabriella Farina: no conflicts of interest; Massimiliano Bonifacio: received honoraria from Novartis, Bristol Myers Squibb, Pfizer, Incyte, Ascentage Pharma, and Amgen; Elena Maria Elli: no conflicts of interest; Angelo Gardellini: no conflicts of interest; Valerio De Stefano: received honoraria from AbbVie, Bristol Myers Squibb, and Novartis; Giovanni Caocci: no conflicts of interest; Antonietta Pia Falcone: no conflicts of interest; Daniele Vallisa: no conflicts of interest; Marco Brociner: no conflicts of interest; Mario Tiribelli: received honoraria from Novartis, Bristol Myers Squibb, Incyte, Pfizer, and GSK; Gianni Binotto: honoraria from Novartis, Bristol Myers Squibb, Incyte, Pfizer, and AOP; Barbara Pocali: no conflicts of interest; Francesco Cavazzini: no conflicts of interest; Simona Tomassetti: no conflicts of interest; Francesca Lunghi: no conflicts of interest; Mauro Di Ianni: no conflicts of interest; Alessandro Allegra: no conflicts of interest; Barbara Anaclerio: no conflicts of interest; Serena Mazzotta: no conflicts of interest; Nicola Orofino: no conflicts of interest; Filippo Gherlinzoni: no conflicts of interest; Chiara Castiglioni: employee of Novartis Farma S.P.A.; Marina Landoni: employee of Novartis Farma S.P.A.; Diletta Valsecchi: employee of Novartis Farma S.P.A.; Michela Magnoli: employee of OPIS S.r.l.; Paola Guglielmelli: honoraria for lectures, presentations, speakers bureaus, manuscript writing, and educational events from Novartis, AbbVie, GSK, and AOP Orphan as well as participation on the advisory board of Novartis, Incyte, and GSK; Francesco Passamonti: honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, and educational events from Novartis, Bristol Myers Squibb, AbbVie, GSK, Janssen, and AOP Orphan as well as participation on the advisory board of Novartis, Bristol Myers Squibb/Celgene, GSK, AbbVie, AOP Orphan, Janssen, Karyiopharma, Kyowa Kirin and MEI, Sumitomo, and Kartos.

Figures

FIGURE 1
FIGURE 1
Patient disposition in the ROMEI study apatients who performed week 48 or later within the cutoff date). bEleven patients receiving starting dose higher than expected. They were excluded because very few patients belong to this group according to the ruxolitinib dose and platelets value at baseline. Note: This interim analysis was performed considering enrolled patients who completed the first 12 months of follow ‐up (i.e., patients who performed week 48 [visit 7] or later or patients who discontinued ruxolitinib treatment before but still under observation) or prematurely discontinued the study by December 31, 2022 (i.e., cutoff date of the present interim analysis). EQ‐5D‐5L indicates EuroQol 5 Dimension 5 Level; IA, interim analysis; MPN‐10, myeloproliferative neoplasm‐10; TSS, total symptom score.
FIGURE 2
FIGURE 2
Plot of the mean daily dose of ruxolitinib by month by ruxolitinib expected starting dose group in the eligible population. The mean daily dose was computed dividing the cumulative total dose of ruxolitinib by the number of days in each month (i.e., 4 weeks). If patient discontinued treatment (temporarily or permanently), both treated and not treated days were considered for the mean daily dose computation.
FIGURE 3
FIGURE 3
Kaplan–Meier plot showing time to permanent discontinuation by ruxolitinib expected starting dose group in the eligible population. Dots represent censors. Patients at risk are patients who had no censored observation and did not yet permanently discontinue the treatment at the considered timepoint.
FIGURE 4
FIGURE 4
Reverse Kaplan–Meier plot of time to first spleen response based on IWG‐MRT criteria by ruxolitinib expected starting dose group in the eligible population. Dots represent censors. Patients at risk are patients eligible for at least one spleen response evaluation (i.e., patients with manual palpation performed both at baseline and at least at one postbaseline visit and without baseline splenomegaly <5 cm) who had no censored observation and did not have spleen response at the considered timepoint yet. Patients with a baseline splenomegaly that is palpable at <5 cm were not eligible for spleen response. IWG‐MRT indicates International Working Group‐Myeloproliferative Neoplasms Research and Treatment.
FIGURE 5
FIGURE 5
Kaplan–Meier plot of overall survival by the ruxolitinib expected starting dose group in the eligible population. Dots represent censors. Patients at risk are patients who have no censored observation and were alive at the considered timepoint yet.
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