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Cattaneo, C.1; Gramegna, D.1; Busca, A.2; Farina, F.3; Candoni, A.4; Piedimonte, M.5; Fracchiolla, N. S.6; Pagani, C.1; Del Principe, M. I.7; Tisi, M. C.8; Maracci, L.9; Fanci, R.10; Ballanti, S.11; Spolzino, A.12; Criscuolo, M.13; Marchesi, F.14; Nadali, G.15; Delia, M.16; Picardi, M.17; Sciumé, M.1; Tumbarello, M.18; Rossi, G.1; Pagano, L.19

doi: 10.1097/01.HS9.0000563348.29099.4a
Poster Session II: Infectious diseases

1Hematology, ASST-Spedali Civili, Brescia

2Stem Cell Transplant Center, AOU Città della Salute e Della Scienza, Turin

3Hematology, San Raffaele Hospital, Milan

4Division of Haematology and Stem Cell Transplantation, University Hospital of Udine, Udine

5Department of Clinical and Molecular Medicine, ”Sant'Andrea“ Hospital-Sapienza, University of Rome, Rome

6U.O. Oncoematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan

7Hematology, Department of BioMedicine and Prevention, Tor Vergata University of Rome, Rome

8Cell Therapy and Hematology, Ospedale San Bortolo, Vicenza

9Hematology, AOU Ospedali Riuniti, Ancona

10Hematology Unit, Careggi Hospital and University of Florence, Florence

11Institute of Hematology, Ospedale S. Maria della Misericordia, Perugia

12Hematology and BMT Unit, Università di Parma, Parma

13Dipartimento di scienze radiologiche, radioterapiche ed ematologiche, Fondazione Policlinico Universitario A. Gemelli-IRCCS

14Hematology and Stem Cell transplantation Unit, IRCCS Regina Elena National Cancer Institute, Rome

15Section of Hematology, Department of Clinical and Experimental Medicine, University of Verona, Verona

16Hematology Section, Dipartimento dell'Emergenza e dei Trapianti d'Organo, University of Bari, Bari

17Department of Advanced Biomedical Science, AOU-Federico II Napoli, Naples

18Institute of Infectious Disease

19Institute of Hematology, Fondazione Policlinico A. Gemelli- IRCCS- Università Cattolica S. Cuore, Rome, Italy

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Isavuconazole (ISV) has been reported as safe and effective in the SECURE trial (Maertens 2016).

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To confirm the efficacy and safety of ISV in hematological patients in a clinical care setting.

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We planned a multicenter retrospective study, collecting all cases of invasive fungal infections (IFI) occurring in hematological patients (pts) treated with ISV in 17 Centers between Jul-16 and Nov-18. IFI were categorized as possible (PS), probable (PB) or proven (PV) according to EORTC/MSG criteria. The impact of age, gender, type and status of disease at IFI (diagnosis [Dx], complete and partial remission [CR/PR], relapse/refractory [r/r]), type of IFI, allogeneic stem cell transplantation (alloSCT), neutropenia and timing of ISV treatment were evaluated.

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One-hundred and twenty-eight pts were enrolled (M/F ratio: 76/52, median age 57y, range 18-80). AL were 88 (68%) (myeloid 57%; lymphoblastic 12%), lymphoma 28 (22%), myeloma 4 (3%), aplastic anemia 3 (2%) and myelodysplastic syndromes 5 (4%) pts. Thirty-one (24%) patients developed IFI at Dx, 54 (42%) while on CR/PR and 43 (34%) with r/r disease; alloSCT pts were 50 (39%). IFI were PS in 54 (42%), PB in 61 (48%) and PV in 13 (10%) cases. Aspergillus spp was responsible for 67 (91%) of PB/PV IFI; in the remaining 7 cases, 1 Rhizomucor and 1 Fusarium spp were isolated and in 5 histologically PV IFI no specific agent was identified. Lung was the more frequent site of IFI (110, 86%), followed by paranasal sinuses (13, 10%). ISV was employed as 1st line therapy in 44 (34%) and as subsequent line in 84 (66%) pts. The median duration of previous treatments was 18d (range 3-1110). Reasons for ISV use were failure in 45 (54%) and intolerance in 17 (20%) of 84 cases. In 17 (20%) ISV was chosen because of the need to switch to oral antifungal agent and in 5 (6%) for a favorable drug-interaction profile. Median duration of ISV treatment was 50d (2-375). Clinical and radiological overall response rate (ORR) was 82 of 118 evaluable pts (69%); it was similar when using ISV as 2nd line with refractory IFI or not (respectively: 67% vs 77%). In multivariate analysis, underlying disease status was confirmed as a predictive factor for ORR to ISV (rec/ref HR 0.259, CI 0.111-0.604). After a median follow-up of 4.2mo, 44 (34%) pts died; IFI-attributable mortality was 13/128 (10%). The estimated 1-year overall survival (OS) from IFI diagnosis of the entire cohort was 50% (CI 0.22-0.45); figures were similar for PS vs PB/PV IFI (52.8% vs 48.7%), AL vs no AL (49% vs 51%) and first vs subsequent line use of ISV (49% vs 51%). OS was significantly lower for pts with refractory IFI (36% vs 58%, p = 0.05) (Fig.1), with r/r hematological disease (r/r 19% vs CR/PR 71%, p = 0.0007, or vs Dx 59%, p = 0.016) and in alloSCT pts (38% vs 58%, p = 0.029). Response to ISV was associated to better OS (HR 0.102, CI 0.04-0.26), while r/r disease showed a trend toward statistically significant negative impact on OS (rel/ref HR 2.344, CI 0.932-5.899). Adverse events (AE) were reported in 15/128 pts (11.7%) (hepatic in 5, cutaneous in 3, gastroenteric in 7 and hypokaliemia in 3); grade 3-4 AE were reported in 5 (4%) cases and led to permanent ISV discontinuation.



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ISV is used in hematological pts also in diseases other than acute myeloid leukemia and it is overall well tolerated. ORR to ISV is at least comparable with other antifungal agents. Having an IFI refractory to other antifungal agents does not seem to compromise the response to ISV, although this condition, together with a r/r underlying disease, negatively impacts on survival.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.