Caspofungin Primary Antifungal Prophylaxis in Acute Leukemia Patients During Induction Therapy: Results of a Prospective Phase II Multicentric Study (ProfilC Study).
Authors: Cattaneo Chiara , Monte Simona , Algarotti Alessandra , Audisio Ernesta , Borlenghi Erika , Bottazzi Barbara , Campiotti Leonardo , Cerqui Elisa , Micò Caterina , Romero Marilena , Salvi Flavia , Salvi Anna , Tognoni Gianni , Mantovani Alberto , Chisesi Teodoro , Levis Alessandro , Deliliers Giorgio Lambertenghi , Pogliani Enrico , Rambaldi Alessandro , Rossi Giuseppe 
Published: October 2019

Abstract 1638

Poster Board I-664

Background

The need for antifungal prophylaxis in acute leukemia (AL) is a very debated topic, considering its potential of inducing resistant strains and of impairing detection of Aspergillus antigen as well as cost-efficacy balance. Targeted prophylaxis, focused on patients (pts) with high risk diseases (e.g. AL during induction therapy), seems to be the most promising strategy. Caspofungin is a well-tolerated echinocandin, with a different mechanism of action with respect to azoles and amphotericin B. Pentraxin 3 (PTX3) belongs to the superfamily of pentraxins acute-phase reactants and may play a protective role against Aspergillus spp (Garlanda et al, Nature 2002).

Aims

To determine the incidence of invasive fungal infections (IFIs) and invasive aspergillosis (IA), the efficacy and safety of caspofungin as primary antifungal prophylaxis during AL induction and to evaluate PTX3 levels as in vivo predictive tool for IFI development.

Patients and Methods

From Jan-07 to Jan-09, the incidence of IFIs and IA during induction was evaluated among all pts with acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) registered in NILG (Northern Italy Leukemia Group) protocols. Ninety-three pts entered the prospective ProfilC protocol and received Caspofungin prophylaxis (70 mg i.v. d1, then 50 mg i.v./d till leukemia remission). ProfilC epidemiological data were compared with those observed among 82 pts not assigned to ProfilC and treated according to the standard prophylactic (SP) policy adopted by each center (67 itraconazole, 10 fluconazole, 1 posaconazole, 4 no prophylaxis). PTX3 blood levels could be evaluated in 90 pts.

Results

Considering all 175 pts, M/F ratio was 103/72, median age was 50 (range 18-73); AML/ALL ratio was 138/37. Overall 32 IFIs (18.3%) were observed, 10 probable/proven (5.7%) (8 IA, 1 Candida spp and 1 G. capitatum bacteremias) and 22 possible (12.6%) according to EORTC/MSG criteria. IFIs (probable/proven and possible) were more frequent in AML (6.5% and 14.5%) than ALL (2.7% and 5.4%). Probable/proven IAs were not seen in ALL. The incidence of probable/proven or possible IFIs between ProfilC pts and those treated with SP was 7.5% and 9.7% vs 3.7% and 15.9%, respectively. Specifically, probable/proven or possible IAs were 5.4% and 8.6% in ProfilC group and 3.7% and 14.6% in SP group, respectively. These data show a lower, albeit not statistically significantly, incidence of IFI and IA in ProfilC pts. Fifteen out of the 175 (8.6%) pts died (ProfilC: 9.7%, SP: 7.3%, p=ns) with only one death due to IFI (G. capitatum sepsis). None of the 8 pts with IA died. Five pts experienced WHO grade >2 toxicity (3 hepatic, 1 skin, 1 hepatic and renal), 3 receiving Caspofungin and 2 itraconazole. One of the 5 pts died (itraconazole) of hepato-renal failure. A trend towards an association between lower PTX3 levels and IFI development was shown, since 13.8% of pts with PTX3 levels >10 ng/ml had IFI (probable: 3.4%), compared to 27.8% of those with '10 ng/ml (probable 8.2%).

Conclusions

Anti-Aspergillus oriented prophylaxis in AL pts was standard policy at most NILG centers. The incidence and letality of probable/proven IFIs and IA were lower than expected and reported by others. Given this epidemiological scenario, the superiority of one drug with respect to others is difficult to demonstrate. Caspofungin was well tolerated during induction and was at least as effective as other prophylactic agents. It may be particularly suited for AL pts with impaired intestinal absorption. High levels of PTX3 (>10 ng/ml) could be protective against IFI/IA, suggesting that PTX3 could be used to identify a very high risk pts population in which an intensified strategy of prophylaxis may be worth testing.

Disclosures

Off Label Use: Caspofungin as antifungal prophylaxis. Rossi:Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees.