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. 2024 Dec 15;130(24):4257-4266.
doi: 10.1002/cncr.35489. Epub 2024 Jul 30.

Clinical outcomes of ruxolitinib treatment in 595 intermediate-1 risk patients with myelofibrosis: The RUX-MF Real-World Study

Francesca Palandri  1 , Elena M Elli  2 , Erika Morsia  3 , Giulia Benevolo  4 , Mario Tiribelli  5 , Eloise Beggiato  6 , Massimiliano Bonifacio  7 , Mirko Farina  8 , Bruno Martino  9 , Giovanni Caocci  10 , Novella Pugliese  11 , Alessia Tieghi  12 , Monica Crugnola  13 , Gianni Binotto  14 , Francesco Cavazzini  15 , Elisabetta Abruzzese  16 , Alessandra Iurlo  17 , Alessandro Isidori  18 , Costanza Bosi  19 , Veronica Guglielmana  2 , Marta Venturi  20 , Alessandra Dedola  20 , Michele Loffredo  20 , Gabriele Fontana  20 , Andrea Duminuco  21 , Alessia Moioli  7 , Luca Tosoni  5 , Emilia Scalzulli  22 , Daniele Cattaneo  17 , Roberto M Lemoli  23   24 , Daniela Cilloni  25 , Monica Bocchia  26 , Fabrizio Pane  11 , Florian H Heidel  27 , Nicola Vianelli  1 , Michele Cavo  1   20 , Giuseppe A Palumbo  28 , Filippo Branzanti  20 , Massimo Breccia  22
Affiliations

Clinical outcomes of ruxolitinib treatment in 595 intermediate-1 risk patients with myelofibrosis: The RUX-MF Real-World Study

Francesca Palandri et al. Cancer. .

Abstract

Background: Ruxolitinib (RUX) is a JAK1/2 inhibitor approved for the therapy of myelofibrosis (MF) based on clinical trials including only intermediate2-high risk (INT2/HIGH) patients. However, RUX is commonly used in intermediate-1 (INT1) patients, with scarce information on responses and outcome.

Methods: The authors investigated the benefit of RUX in 1055 MF patients, included in the "RUX-MF" retrospective study.

Results: At baseline (BL), 595 (56.2%) patients were at INT1-risk according to DIPSS (PMF) or MYSEC-PM (SMF). The spleen was palpable at <5 cm, between 5 and 10 cm, and >10 cm below costal margin in 5.9%, 47.4%, and 39.7% of patients, respectively; 300 (54.1%) were highly symptomatic (total symptom score ≥20). High-molecular-risk (HMR) mutations (IDH1/2, ASXL-1, SRSF2, EZH2, U2AF1Q157) were detected in 77/167 patients. A total of 101 (19.2%) patients had ≥1 cytopenia (Hb < 10 g/dL: n.36; PLT <100 x 109/L: n = 43; white blood cells <4 x 109/L: n = 40). After 6 months on RUX, IWG-MRT-defined spleen and symptoms response rates were 26.8% and 67.9%, respectively. In univariate analysis, predictors of SR at 6 months were no HMR mutations odds ratio [OR], 2.0, p = .05], no cytopenia (OR, 2.10; p = .01), and blasts <1% (OR, 1.91; p = .01). In multivariate analysis, absence of HMR maintained a significant association (OR, 2.1 [1.12-3.76]; p = .01).

Conclusions: In INT1 patients, responses were more frequent and durable, whereas toxicity rates were lower compared to INT2/high-risk patients. Presence of HMR mutations, cytopenia, and peripheral blasts identified less-responsive INT1 patients, who may benefit for alternative therapeutic strategies.

Keywords: DIPSS score; JAK2 mutation; intermediate‐1; myelofibrosis; ruxolitinib.

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Conflict of interest statement

Francesca Palandri reports consultancy and honoraria from Novartis, Celgene, AOP, Sierra Oncology, and CTI. Giulia Benevolo reports honoraria from Novartis, Janssen, Amgen, Takeda, and BMS. Alessandra Iurlo reports honoraria from Novartis, BMS, Pfizer, and Incyte. Massimo Breccia reports honoraria from Novartis, BMS, Pfizer, Incyte. Massimiliano Bonifacio reports honoraria from Novartis, BMS, Pfizer, and Incyte. Monica Crugnola reports honoraria from Novartis and Amgen. Gianni Binotto reports honoraria from Novartis, Incyte, BMS‐Celgene, and Pfizer. Roberto M. Lemoli reports honoraria from Jazz, Pfizer, AbbVie, BMS, Sanofi, and StemLine. Fabrizio Pane reports honoraria from Incyte, Novartis, Jazz, BMS‐Celgene, Amgen, and Gilead. Michele Cavo acted as consultant and received honoraria from Jannsen, BMS Celgene, SanoFI, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, and Adaptive. Giuseppe A. Palumbo reports consultancy and honoraria from Abbvie, AOP, AstraZeneca, BMS, Incyte, GSK, Morphosys, and Novartis. Michele Cavo acted as consultant and received honoraria from Jannsen, BMS Celgene, SanoFI, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, and Adaptive.

Figures

FIGURE 1
FIGURE 1
Characteristics associated to spleen response at 6 months in intermediate‐1 patients.* *Using Pearson’s correlation test: white blood cell (WBC) count <25 x 109/L correlates with blasts <1%; platelet (PLT) count <100 x 109/L; and hemoglobin (Hb) <10 g/dL correlate with no cytopenia. (a) Including high‐molecular risk (HMR) mutations; (b) excluding HMR mutations.
FIGURE 2
FIGURE 2
Overall survival (a) and event‐free survival (b) of intermediate‐1 (blue line) compared to intermediate‐2/high‐risk patients (red line).
See this image and copyright information in PMC

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