Deferasirox for transfusion-dependent patients with myelodysplastic syndromes: safety, efficacy, and beyond (GIMEMA MDS0306 Trial)
Corresponding Author
Emanuele Angelucci
Hematology and Bone Marrow Transplantation Unit, Ospedale Oncologico di Riferimento Regionale “Armando Businco”, Cagliari, Italy
Correspondence Emanuele Angelucci, MD, Hematology and Bone Marrow Transplantation Unit, Ospedale Oncologico di Riferimento Regionale “Armando Businco”, Via Edward Jenner Cagliari, 09121 Italy. Tel: +39 070 6092061; Fax: +39 070 6092065;
e-mail: [email protected]
Search for more papers by this authorValeria Santini
Division of Hematology, University of Florence, Florence, Italy
Search for more papers by this authorAnna Angela Di Tucci
Hematology and Bone Marrow Transplantation Unit, Ospedale Oncologico di Riferimento Regionale “Armando Businco”, Cagliari, Italy
Search for more papers by this authorGiulia Quaresmini
Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
Search for more papers by this authorCarlo Finelli
Division of Hematology, Policlinico S. Orsola-Malpighi, Bologna, Italy
Search for more papers by this authorAntonio Volpe
Division of Hematology, San Giuseppe Moscati Hospital, Avellino, Italy
Search for more papers by this authorGiovanni Quarta
Division of Hematology, Ospedale A. Perrino, Brindisi, Italy
Search for more papers by this authorFlavia Rivellini
UO Medicina Interna e Onco-Ematologica P.O. “Umberto I”, Nocera Inferiore, Italy
Search for more papers by this authorGrazia Sanpaolo
Division of Hematology, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
Search for more papers by this authorDaniela Cilloni
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
Search for more papers by this authorFlavia Salvi
Division of Hematology, A.O. Nazionale Santi Antonio e Biagio e C. Arrigo, Alessandria, Italy
Search for more papers by this authorGiovanni Caocci
Bone Marrow Transplantation Center, R. Binaghi Hospital, Cagliari, Italy
Search for more papers by this authorAlfredo Molteni
Division of Hematology, Niguarda Ca’ Granda Hospital, Milan, Italy
Search for more papers by this authorDaniele Vallisa
Division of Medical Oncology and Hematology, Hospital of Piacenza, Piacenza, Italy
Search for more papers by this authorMaria Teresa Voso
Division of Hematology, Università Cattolica del Sacro Cuore, Rome, Italy
Search for more papers by this authorSusanna Fenu
Division of Hematology, San Giovanni Hospital, Rome, Italy
Search for more papers by this authorGiancarlo Latte
Division of Hematology, S. Francesco Hospital, Nuoro, Italy
Search for more papers by this authorGiuliana Alimena
Division of Hematology, “Sapienza”University of Rome, Rome, Italy
Search for more papers by this authorSergio Storti
Division of Hematology and Medical Oncology, Campobasso University, Campobasso, Italy
Search for more papers by this authorAlfonso Piciocchi
GIMEMA Data Center, GIMEMA Foundation, Rome, Italy
Search for more papers by this authorMarco Vignetti
GIMEMA Data Center, GIMEMA Foundation, Rome, Italy
Search for more papers by this authorCorresponding Author
Emanuele Angelucci
Hematology and Bone Marrow Transplantation Unit, Ospedale Oncologico di Riferimento Regionale “Armando Businco”, Cagliari, Italy
Correspondence Emanuele Angelucci, MD, Hematology and Bone Marrow Transplantation Unit, Ospedale Oncologico di Riferimento Regionale “Armando Businco”, Via Edward Jenner Cagliari, 09121 Italy. Tel: +39 070 6092061; Fax: +39 070 6092065;
e-mail: [email protected]
Search for more papers by this authorValeria Santini
Division of Hematology, University of Florence, Florence, Italy
Search for more papers by this authorAnna Angela Di Tucci
Hematology and Bone Marrow Transplantation Unit, Ospedale Oncologico di Riferimento Regionale “Armando Businco”, Cagliari, Italy
Search for more papers by this authorGiulia Quaresmini
Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
Search for more papers by this authorCarlo Finelli
Division of Hematology, Policlinico S. Orsola-Malpighi, Bologna, Italy
Search for more papers by this authorAntonio Volpe
Division of Hematology, San Giuseppe Moscati Hospital, Avellino, Italy
Search for more papers by this authorGiovanni Quarta
Division of Hematology, Ospedale A. Perrino, Brindisi, Italy
Search for more papers by this authorFlavia Rivellini
UO Medicina Interna e Onco-Ematologica P.O. “Umberto I”, Nocera Inferiore, Italy
Search for more papers by this authorGrazia Sanpaolo
Division of Hematology, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
Search for more papers by this authorDaniela Cilloni
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
Search for more papers by this authorFlavia Salvi
Division of Hematology, A.O. Nazionale Santi Antonio e Biagio e C. Arrigo, Alessandria, Italy
Search for more papers by this authorGiovanni Caocci
Bone Marrow Transplantation Center, R. Binaghi Hospital, Cagliari, Italy
Search for more papers by this authorAlfredo Molteni
Division of Hematology, Niguarda Ca’ Granda Hospital, Milan, Italy
Search for more papers by this authorDaniele Vallisa
Division of Medical Oncology and Hematology, Hospital of Piacenza, Piacenza, Italy
Search for more papers by this authorMaria Teresa Voso
Division of Hematology, Università Cattolica del Sacro Cuore, Rome, Italy
Search for more papers by this authorSusanna Fenu
Division of Hematology, San Giovanni Hospital, Rome, Italy
Search for more papers by this authorGiancarlo Latte
Division of Hematology, S. Francesco Hospital, Nuoro, Italy
Search for more papers by this authorGiuliana Alimena
Division of Hematology, “Sapienza”University of Rome, Rome, Italy
Search for more papers by this authorSergio Storti
Division of Hematology and Medical Oncology, Campobasso University, Campobasso, Italy
Search for more papers by this authorAlfonso Piciocchi
GIMEMA Data Center, GIMEMA Foundation, Rome, Italy
Search for more papers by this authorMarco Vignetti
GIMEMA Data Center, GIMEMA Foundation, Rome, Italy
Search for more papers by this authorAbstract
Background
In the absence of randomized, controlled trial data to support iron chelation therapy in transfusion-dependent patients with myelodysplastic syndromes (MDS), continued evidence from large prospective clinical trials evaluating the efficacy and safety of iron chelation therapy in this patient population is warranted.
Methods
The safety and efficacy of deferasirox was examined in a prospective, open-label, single-arm, multicenter trial of transfusion-dependent patients with International Prognostic Scoring System low- or intermediate-1-risk MDS and evidence of transfusion-related iron overload. The effects of deferasirox therapy on hematological response and disease progression were also examined.
Results
Of 159 participants enrolled from 37 Italian centers, 152 received ≥1 dose of deferasirox (initiated at 10–20 mg/kg/day and titrated as appropriate), and 68 completed the study. Of 84 patients who discontinued deferasirox therapy, 22 died during the trial, and 28 withdrew due to an adverse event (AE). Fourteen treatment-related grade 3 AEs occurred in 11 patients, whereas no grade 4 or 5 drug-related AEs were reported. Significant risks for dropout were a higher serum ferritin level at baseline, a higher MDS-Specific Comorbidity Index, and a shorter diagnosis–enrollment interval. Median serum ferritin level fell from 1966 ng/mL to 1475 ng/mL (P < 0.0001). The cumulative incidence of transfusion independence, adjusted for death and disease progression, was 2.6%, 12.3%, and 15.5% after 6, 9, and 12 months, respectively.
Conclusions
Deferasirox therapy in transfusion-dependent patients with MDS was moderately well tolerated and effectively lowered serum ferritin levels. Positive hematological responses were observed, and a subset of patients achieved transfusion independence.
Supporting Information
| Filename | Description |
|---|---|
| ejh12300-sup-0001-SuppinfoS1-S7.docxWord document, 372 KB | Figure S1. Related and non-related adverse events by organ system. Figure S2. Ferritin values over time after start of deferasirox. Figure S3. Alanine aminotransferase values over time after start of deferasirox. Figure S4. Creatinine values over time after start of deferasirox. Figure S5. Cumulative incidence estimation of transfusion independence in competition with patient death and disease progression. Table S1. Related grade 3 adverse events. Table S2. Non-related grade 4–5 adverse events. Appendix 1. Participating centers and investigators. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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