Cancers (Jul 2023)
Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study
- Francesca Palandri,
- Elena Rossi,
- Giuseppe Auteri,
- Massimo Breccia,
- Simona Paglia,
- Giulia Benevolo,
- Elena M. Elli,
- Francesco Cavazzini,
- Gianni Binotto,
- Alessia Tieghi,
- Mario Tiribelli,
- Florian H. Heidel,
- Massimiliano Bonifacio,
- Novella Pugliese,
- Giovanni Caocci,
- Monica Crugnola,
- Francesco Mendicino,
- Alessandra D'Addio,
- Simona Tomassetti,
- Bruno Martino,
- Nicola Polverelli,
- Sara Ceglie,
- Camilla Mazzoni,
- Rikard Mullai,
- Alessia Ripamonti,
- Bruno Garibaldi,
- Fabrizio Pane,
- Antonio Cuneo,
- Mauro Krampera,
- Gianpietro Semenzato,
- Roberto M. Lemoli,
- Nicola Vianelli,
- Giuseppe A. Palumbo,
- Alessandro Andriani,
- Michele Cavo,
- Roberto Latagliata,
- Valerio De Stefano
Affiliations
- Francesca Palandri
- Istituto di Ematologia “Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Elena Rossi
- Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University School of Medicine, 00168 Rome, Italy
- Giuseppe Auteri
- Istituto di Ematologia “Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Massimo Breccia
- Division of Cellular Biotechnologies and Hematology, University Sapienza, 00161 Rome, Italy
- Simona Paglia
- Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, 40126 Bologna, Italy
- Giulia Benevolo
- Division of Hematology, Città della Salute e della Scienza Hospital, 10126 Torino, Italy
- Elena M. Elli
- Hematology Division, San Gerardo Hospital, ASST Monza, 20900 Monza, Italy
- Francesco Cavazzini
- Division of Hematology, University of Ferrara, 44121 Ferrara, Italy
- Gianni Binotto
- Unit of Hematology and Clinical Immunology, University of Padova, 35020 Padova, Italy
- Alessia Tieghi
- Department of Hematology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy
- Mario Tiribelli
- Division of Hematology and BMT, Azienda Sanitaria Universitaria Integrata di Udine, 33100 Udine, Italy
- Florian H. Heidel
- Innere Medicine C, Universitätsmedizin Greifswald, 17475 Greifswald, Germany
- Massimiliano Bonifacio
- Hematology and Bone Marrow Transplant Unit, Section of Biomedicine of Innovation, Department of Engineering for Innovative Medicine, University of Verona, 37134 Verona, Italy
- Novella Pugliese
- Department of Clinical Medicine and Surgery, Hematology Section, University of Naples “Federico II”, 80131 Naples, Italy
- Giovanni Caocci
- Hematology Unit, Department of Medical Sciences, University of Cagliari, 09124 Cagliari, Italy
- Monica Crugnola
- Division of Hematology, Azienda Ospedaliero-Universitaria di Parma, 43126 Parma, Italy
- Francesco Mendicino
- Unit of Hematology, Hospital of Cosenza, 87100 Cosenza, Italy
- Alessandra D'Addio
- Division of Hematology, Onco-Hematologic Department, AUSL della Romagna, 47923 Ravenna, Italy
- Simona Tomassetti
- Hematology Unit, Infermi Hospital Rimini, 47923 Rimini, Italy
- Bruno Martino
- Division of Hematology, Azienda Ospedaliera ‘Bianchi Melacrino Morelli’, 89133 Reggio Calabria, Italy
- Nicola Polverelli
- Unit of Blood Diseases and Stem Cell Transplantation, ASST Spedali Civili di Brescia, 25123 Brescia, Italy
- Sara Ceglie
- Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University School of Medicine, 00168 Rome, Italy
- Camilla Mazzoni
- Istituto di Ematologia “Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Rikard Mullai
- Division of Hematology and BMT, Azienda Sanitaria Universitaria Integrata di Udine, 33100 Udine, Italy
- Alessia Ripamonti
- Hematology Division, San Gerardo Hospital, ASST Monza, 20900 Monza, Italy
- Bruno Garibaldi
- Postgraduate School of Hematology, University of Catania, 90121 Catania, Italy
- Fabrizio Pane
- Department of Clinical Medicine and Surgery, Hematology Section, University of Naples “Federico II”, 80131 Naples, Italy
- Antonio Cuneo
- Division of Hematology, University of Ferrara, 44121 Ferrara, Italy
- Mauro Krampera
- Hematology and Bone Marrow Transplant Unit, Section of Biomedicine of Innovation, Department of Engineering for Innovative Medicine, University of Verona, 37134 Verona, Italy
- Gianpietro Semenzato
- Unit of Hematology and Clinical Immunology, University of Padova, 35020 Padova, Italy
- Roberto M. Lemoli
- Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genova, 16126 Genova, Italy
- Nicola Vianelli
- Istituto di Ematologia “Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Giuseppe A. Palumbo
- Department of Scienze Mediche, Chirurgiche e Tecnologie Avanzate “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy
- Alessandro Andriani
- Villa Betania Hospital, 00165 Roma, Italy
- Michele Cavo
- Istituto di Ematologia “Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Roberto Latagliata
- Hematology Unit, Ospedale Belcolle, 01100 Viterbo, Italy
- Valerio De Stefano
- Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University School of Medicine, 00168 Rome, Italy
- DOI
- https://doi.org/10.3390/cancers15143706
- Journal volume & issue
-
Vol. 15,
no. 14
p. 3706
Abstract
In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients’ triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p < 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised.
Keywords