Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome-Reference-Cited by-同舟云学术

Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome

Published:2023-03-18 Issue:11 Volume:129 Page:1704-1713
ISSN:0008-543X
Container-title:Cancer
language:en
Short-container-title:Cancer

Author:

Palandri Francesca¹^ORCID,Breccia Massimo²^ORCID,Mazzoni Camilla¹³^ORCID,Auteri Giuseppe¹³,Elli Elena Maria⁴^ORCID,Trawinska Malgorzata M.⁵,Polverelli Nicola⁶^ORCID,Tiribelli Mario⁷^ORCID,Benevolo Giulia⁸^ORCID,Iurlo Alessandra⁹^ORCID,Tieghi Alessia¹⁰,Heidel Florian H.¹¹,Caocci Giovanni¹²,Beggiato Eloise⁸,Binotto Gianni¹³,Cavazzini Francesco¹⁴,Miglino Maurizio¹⁵¹⁶,Bosi Costanza¹⁷,Crugnola Monica¹⁸,Bocchia Monica¹⁹,Martino Bruno²⁰,Pugliese Novella²¹^ORCID,Biondo Mattia¹³,Venturi Marta¹³,Scaffidi Luigi²²,Isidori Alessandro²³,Cattaneo Daniele⁹,Krampera Mauro²²,Pane Fabrizio²¹,Cilloni Daniela²⁴,Semenzato Gianpietro¹³,Lemoli Roberto M.¹⁵¹⁶,Cuneo Antonio¹⁴,Abruzzese Elisabetta²⁵^ORCID,Bartoletti Daniela¹³,Paglia Simona¹,Vianelli Nicola¹,Cavo Michele¹³,Bonifacio Massimiliano²¹^ORCID,Palumbo Giuseppe A.²⁶

Affiliation:

1. Istituto di Ematologia “Seràgnoli” IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna Italy

2. Division of Cellular Biotechnologies and Hematology University Sapienza Rome Italy

3. Dipartimento di Medicina Specialistica Diagnostica e Sperimentale Università di Bologna Bologna Italy

4. Hematology Division San Gerardo Hospital ASST Monza Monza Italy

5. Hematology Sant’Eugenio Hospital Tor Vergata University Roma Italy

6. Unit of Blood Diseases and Stem Cell Transplantation ASST Spedali Civili di Brescia Brescia Italy

7. Division of Hematology and BMT Azienda Sanitaria Universitaria Integrata di Udine Udine Italy

8. Division of Hematology Città della Salute e della Scienza Hospital Torino Italy

9. Hematology Division Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy

10. Department of Hematology Azienda USL ‐ IRCCS di Reggio Emilia Reggio Emilia Italy

11. Innere Medicine C Universitätsmedizin Greifswald Greifswald Germany

12. Hematology Unit Department of Medical Sciences University of Cagliari Cagliari Italy

13. Unit of Hematology and Clinical Immunology University of Padova Padova Italy

14. Division of Hematology University of Ferrara Ferrara Italy

15. Clinic of Hematology Department of Internal Medicine (DiMI) University of Genoa Genova Italy

16. IRCCS Policlinico San Martino Genova Italy

17. Division of Haematology AUSL di Piacenza Piacenza Italy

18. Division of Hematology Azienda Ospedaliero‐Universitaria di Parma Parma Italy

19. Hematology Unit Azienda Ospedaliera Universitaria Senese University of Siena Siena Italy

20. Division of Hematology Azienda Ospedaliera 'Bianchi Melacrino Morelli' Reggio Calabria Italy

21. Department of Clinical Medicine and Surgery Hematology Section University of Naples "Federico II" Naples Italy

22. Section of Hematology Department of Medicine University of Verona Verona Italy

23. Haematology and Haematopoietic Stem Cell Transplant Center AORMN Hospital Pesaro Italy

24. Department of Clinical and Biological Sciences University of Turin Turin Italy

25. Hematology S. Eugenio Hospital ASLRoma2 Rome Italy

26. Department of Scienze Mediche Chirurgiche e Tecnologie Avanzate “G.F. Ingrassia” University of Catania Catania Italy

Abstract

AbstractBackgroundPatients with cytopenic myelofibrosis (MF) have more limited therapeutic options and poorer prognoses compared with patients with the myeloproliferative phenotype.Aims and MethodsPrognostic correlates of cytopenic phenotype were explored in 886 ruxolitinib‐treated patients with primary/secondary MF (PMF/SMF) included in the RUX‐MF retrospective study. Cytopenia was defined as: leukocyte count <4 × 109/L and/or hemoglobin <11/<10 g/dL (males/females) and/or platelets <100 × 109/L.ResultsOverall, 407 (45.9%) patients had a cytopenic MF, including 249 (52.4%) with PMF. In multivariable analysis, high molecular risk mutations (p = .04), intermediate 2/high Dynamic International Prognostic Score System (p < .001) and intermediate 2/high Myelofibrosis Secondary to Polycythemia Vera and Essential Thrombocythemia Prognostic Model (p < .001) remained associated with cytopenic MF in the overall cohort, PMF, and SMF, respectively. Patients with cytopenia received lower average ruxolitinib at the starting (25.2 mg/day vs. 30.2 mg/day, p < .001) and overall doses (23.6 mg/day vs. 26.8 mg/day, p < .001) and achieved lower rates of spleen (26.5% vs. 34.1%, p = .04) and symptom (59.8% vs. 68.8%, p = .008) responses at 6 months compared with patients with the proliferative phenotype. Patients with cytopenia also had higher rates of thrombocytopenia at 3 months (31.1% vs. 18.8%, p < .001) but lower rates of anemia (65.6% vs. 57.7%, p = .02 at 3 months and 56.6% vs. 23.9% at 6 months, p < .001). After competing risk analysis, the cumulative incidence of ruxolitinib discontinuation at 5 years was 57% and 38% in patients with cytopenia and the proliferative phenotype (p < .001), whereas cumulative incidence of leukemic transformation was similar (p = .06). In Cox regression analysis adjusted for Dynamic International Prognostic Score System score, survival was significantly shorter in patients with cytopenia (p < .001).ConclusionsCytopenic MF has a lower probability of therapeutic success with ruxolitinib as monotherapy and worse outcome. These patients should be considered for alternative therapeutic strategies.

Funder

Ministero della Salute

Publisher

Wiley

Subject

Cancer Research,Oncology

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.34722

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