ISAVUCONAZOLE IN HEMATOLOGICAL PATIENTS: FINAL RESULTS OF A REAL-LIFE MULTICENTER SEIFEM (SORVEGLIANZA EPIDEMIOLOGICA DELLE INFEZIONI NELLE EMOPATIE) STUDY
Author(s): ,
Chiara Cattaneo
Affiliations:
Hematology,ASST-Spedali Civili,Brescia,Italy
,
Doriana Gramegna
Affiliations:
Hematology,ASST-Spedali Civili,Brescia,Italy
,
Alessandro Busca
Affiliations:
Stem Cell Transplant Center,AOU Città della Salute e Della Scienza,Turin,Italy
,
Francesca Farina
Affiliations:
Hematology,San Raffaele Hospital,Milan,Italy
,
Anna Candoni
Affiliations:
Division of Haematology and Stem Cell Transplantation,University Hospital of Udine,Udine,Italy
,
Monica Piedimonte
Affiliations:
Department of Clinical and Molecular Medicine,'Sant'Andrea' Hospital-Sapienza, University of Rome,Rome,Italy
,
Nicola Stefano Fracchiolla
Affiliations:
U.O. Oncoematologia,Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and University of Milan,Milan,Italy
,
Chiara Pagani
Affiliations:
Hematology,ASST-Spedali Civili,Brescia,Italy
,
Maria Ilaria Del Principe
Affiliations:
Hematology,Department of BioMedicine and Prevention, Tor Vergata University of Rome,Rome,Italy
,
Maria Chiara Tisi
Affiliations:
Cell Therapy and Hematology,Ospedale San Bortolo,Vicenza,Italy
,
Laura Maracci
Affiliations:
Hematology,AOU Ospedali Riuniti,Ancona,Italy
,
Rosa Fanci
Affiliations:
Hematology Unit,Careggi Hospital and University of Florence,Florence,Italy
,
Stelvio Ballanti
Affiliations:
Institute of Hematology,Ospedale S. Maria della Misericordia,Perugia,Italy
,
Angelica Spolzino
Affiliations:
Hematology and BMT Unit,Università di Parma,Parma,Italy
,
Marianna Criscuolo
Affiliations:
Dipartimento di scienze radiologiche, radioterapiche ed ematologiche,Fondazione Policlinico Universitario A. Gemelli-IRCCS,Rome,Italy
,
Francesco Marchesi
Affiliations:
Hematology and Stem Cell transplantation Unit,IRCCS Regina Elena National Cancer Institute,Rome,Italy
,
Gianpaolo Nadali
Affiliations:
Section of Hematology, Department of Clinical and Experimental Medicine,University of Verona,Verona,Italy
,
Mario Delia
Affiliations:
Hematology Section, Dipartimento dell'Emergenza e dei Trapianti d'Organo,University of Bari,Bari,Italy
,
Marco Picardi
Affiliations:
Department of Advanced Biomedical Science,AOU-Federico II Napoli,Naples,Italy
,
Margherita Sciumé
Affiliations:
Hematology,ASST-Spedali Civili,Brescia,Italy
,
Mario Tumbarello
Affiliations:
Institute of Infectious Disease,Fondazione Policlinico A. Gemelli- IRCCS- Università Cattolica S. Cuore,Rome,Italy
,
Giuseppe Rossi
Affiliations:
Hematology,ASST-Spedali Civili,Brescia,Italy
Livio Pagano
Affiliations:
Institute of Hematology,Fondazione Policlinico A. Gemelli- IRCCS- Università Cattolica S. Cuore,Rome,Italy
EHA Library. Cattaneo C. Jun 15, 2019; 266884; PS1267
Chiara Cattaneo
Chiara Cattaneo
Contributions
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Abstract

Abstract: PS1267

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

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

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

Methods
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.

Results
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.

Conclusion
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.

Session topic: 30. Infectious diseases

Keyword(s): Fungal infection, Hematological malignancy, Treatment

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