Revised "iRR6" model in intermediate-1 risk myelofibrosis patients treated with ruxolitinib

Francesca Palandri ¹, Filippo Branzanti ², Massimiliano Bonifacio ³

¹IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.
²Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.
³Department of Engineering for Innovation Medicine, Section of Innovation Biomedicine, Hematology Area, University of Verona, Verona, Italy.
⁴Divisione di Ematologia e Unità Trapianto di Midollo, IRCCS San Gerardo dei Tintori, Monza, Italy.
⁵Hematology Unit, Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy.
⁶Department of Clinical and Experimental Sciences, Unit of Blood Diseases and Stem Cells Transplantation, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy.
⁷Division of Hematology and BMT, Department of Medical Area, University of Udine, Udine, Italy.
⁸University Hematology Division, Città della Salute e della Scienza Hospital, Torino, Italy.
⁹Unit of Hematology, Department of Oncology, University of Torino, Torino, Italy.
¹⁰Division of Hematology, Reggio Calabria, Azienda Ospedaliera "Bianchi Melacrino Morelli", Calabria, Italy.
¹¹Ematologia, Ospedale Businco, Università degli studi di Cagliari, Cagliari, Italy.
¹²Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy.
¹³Department of Hematology, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
¹⁴Haematology and BMT Centre, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
¹⁵Unit of Hematology and Clinical Immunology, University of Padova, Padova, Italy.
¹⁶Division of Hematology, University of Ferrara, Ferrara, Italy.
¹⁷Division of Hematology, Ospedale S. Eugenio, Roma, Italy.
¹⁸Hematology and Stem Cell Transplant Center, AORMN Hospital, Pesaro, Italy.
¹⁹Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Rome, Italy.
²⁰UO Ematologia, AOU Policlinico "G. Rodolico"-San Marco, Catania, Italy.
²¹Department of Internal Medicine (DiMI), Clinic of Hematology, University of Genoa, Genoa, Italy.
²²IRCCS Policlinico San Martino, Genova, Italy.
²³Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
²⁴Hematology Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy.
²⁵Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School (MHH), Hannover, Germany.
²⁶Department of Scienze Mediche, Chirurgiche e Tecnologie Avanzate "G.F. Ingrassia", University of Catania, Catania, Italy.
²⁷Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.

⁰IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.

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August 21, 2025

View abstract on PubMed

Summary

A new iRR6 model refines risk stratification for intermediate-1 myelofibrosis patients, improving identification of those who may benefit from early ruxolitinib therapy adjustments.

Area Of Science

Hematology
Oncology
Clinical Trials

Background

The response to ruxolitinib after 6 months (RR6) model aids in identifying myelofibrosis (MF) patients with poor survival but is less effective for lower-risk groups.
Existing models do not adequately stratify intermediate-1 risk MF patients.

Purpose Of The Study

To validate the RR6 model in intermediate-1 risk MF patients.
To develop a novel risk stratification score specifically for intermediate-1 risk MF patients.

Main Methods

Subanalysis of the RUX-MF study (NCT06516406).
Development of the intermediate-1 specific RR6 (iRR6) model incorporating variables such as ruxolitinib dosing, spleen reduction, and transfusion needs.
Validation of the iRR6 model in an independent cohort.

Main Results

The standard RR6 model failed to differentiate risk within the intermediate-1 MF patient subgroup.
The iRR6 model identified three distinct risk categories (low, intermediate, high) within intermediate-1 MF patients, with significant differences in 5-year overall survival (OS).
The iRR6 model demonstrated successful validation in an independent cohort.

Conclusions

The iRR6 model offers a more precise tool for risk stratification in intermediate-1 MF patients.
This refined model can guide early therapeutic strategy adjustments for improved patient outcomes.

Keywords:

intermediate‐1 post‐ET myelofibrosis post‐PV myelofibrosis primary myelofibrosis ruxolitinib survival score

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