Abstract 1120

Between 2007–2010 we performed a monocentric non-randomized prospective study to compare Vor (orally or IV 200 mg b.i.d.) to Pos (orally 200 mg t.i.d.) as primary prophylactic antifungals in either de novo or relapsed leukemic patients. Most chemotherapy regimens used were those of the French collaborative group GOELAMS. The Vor arm was stopped mid-2008 because of available evidence in favor of Pos. The primary endpoint was the IFI incidence within 60 days after chemotherapy. IFI was diagnosed according to the 2008 EORTC criteria. Secondary endpoints were the 60 days post-chemotherapy death rate and frequency of empirical antifungal therapy. Variables potentially related to IFI incidence and to outcome as LAF rooms HEPA filtrated, cytogenetics risk-profile, diagnosis, disease status, age, duration of neutropenia or prophylaxis were also evaluated. Characteristics of patients at baseline are shown below. The unit of study was a cycle of chemotherapy. Among Vor and Pos treated patients 65.2 and 67% respectively corresponded to induction cycles.

VoriconazolePosaconazolep
N 23 115  
Age (years: median/mean, range) 51.1/58 (26–72) 59/57.6 (20–82) 0.15 
Sex F/M 9/14 34/81 0.4 
AML 20 98 n.s. 
ALL 3 17 n.s. 
Induction 15 77 n.s. 
Consolidation 8 38 n.s. 
De novo 20 103 n.s. 
Refractory/relapsed 3 12 n.s. 
Patients in LAF rooms, HEPA filtered with positive pressure YES/NOT 8/15 53/62 n.s. 
ALL CYCLES *INDUCTION *5/10 *34/43 n.s. 
High/intermediate/low risk cytogenetics 5/9/5 36/57/17 n.s. 
Mean/Median duration of prophylaxis: days 18.4/16 24.1/21 0.1 
Mean-Median duration of ANC < 500/mm3 17.7–16/*19.5–18/**14.5–12 17.9–17/*20.3–20/**13–13.5 n.s. 
all cycles/*induction/**consolidation    
VoriconazolePosaconazolep
N 23 115  
Age (years: median/mean, range) 51.1/58 (26–72) 59/57.6 (20–82) 0.15 
Sex F/M 9/14 34/81 0.4 
AML 20 98 n.s. 
ALL 3 17 n.s. 
Induction 15 77 n.s. 
Consolidation 8 38 n.s. 
De novo 20 103 n.s. 
Refractory/relapsed 3 12 n.s. 
Patients in LAF rooms, HEPA filtered with positive pressure YES/NOT 8/15 53/62 n.s. 
ALL CYCLES *INDUCTION *5/10 *34/43 n.s. 
High/intermediate/low risk cytogenetics 5/9/5 36/57/17 n.s. 
Mean/Median duration of prophylaxis: days 18.4/16 24.1/21 0.1 
Mean-Median duration of ANC < 500/mm3 17.7–16/*19.5–18/**14.5–12 17.9–17/*20.3–20/**13–13.5 n.s. 
all cycles/*induction/**consolidation    
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Results:

IFI was diagnosed in 1/23 (4.4%) and 5/115 (4.4%) cycles respectively of Vor (1 proven C lusitaniae) and Pos (1 proven C krusei, 1 proven C albicans, 3 probable aspergillosis) arms (p 1.0). Five of 6 cases of IFI occurred during inductions and 1 on consolidations without significant difference between the two drugs. Most IFI were observed in patients not placed in LAF rooms. The IFI rate was 1.6% (1/62) and 6.5% (5/77) respectively for patients in LAF and conventional rooms (p 0.2). During induction patients in LAF rooms showed a trend to a lower incidence of IFI (0/39) compared to those in conventional rooms (5/48) (p 0.07), without superiority of Vor or Pos arms. Induction patients in LAF rooms presented respectively no IFI (0/8) and 1 (1/52) in the Vor and Pos arms (p 0.57). Among patients not located in LAF rooms both Pos and Vor arms presented a similar IFI rate, 6.4% (4/58) and 6.6% (1/14) respectively. Although patients with low-risk cytogenetics did not present any IFI, this was not significantly different to patients with intermediate and high-risk cytogenetics (p 0.5), conversely to an IFI incidence significantly higher in relapsed/refractory patients vs those who achieved or persisted in first complete remission (p 0.01). Empirical treatment was administered respectively to 8.7 and 16.5% of patients in the Vor and Pos arms (p 0.5) without difference in the IFI incidence between patients who received it or not. The 60 days death rate was 17.4 and 13 % respectively in the Vor and Pos arms (p=0.5). Patients deceased within 60 days were older than those who survived (p 0.08) and presented more frequently a poor prognosis cytogenetics (p 0.032). Death rate was higher but not significantly different during induction (17.4%) and consolidation (2.1%) (p 0.1). Patients in LAF rooms presented a significantly lower death rate (6.5%) than patients in conventional rooms (19.5%) (p 0.02). Induction patients in LAF rooms deceased less (7.7%) than those in conventional rooms (24.5%) (p 0.05). The 60 days death rate was not significantly different between patients placed or not in LAF rooms receiving either Pos or Vor, but it was significantly different between patients presenting or not an IFI (50 and 88% respectively) (p 0.033). This was confirmed in a multivariate analysis which identified diagnosis of IFI (0.004; OR 20.0) and age (0.02; OR 4.5) as significant prognostic variables of a 60 days death rate. Conclusions: both Pos and Vor present a good similar efficacy in primary prophylaxis of IFI in acute leukemic patients. Poor prognosis patients present a higher rate of IFI and death. Patients located in LAF rooms during induction tend to present a lower IFI incidence and a better survival.

Disclosures:

Off Label Use: Voriconazole use in primary prophylaxis of invasive fungal infections in leukemic patients.

Topics:
posaconazole, systemic mycosis, voriconazole, chemotherapy regimen, antifungal agents, aspergillosis, complete remission, neutropenia, off-label use, surrogate endpoints

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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