TY - JOUR
T1 - Randomized comparison of liposomal amphotericin B versus placebo to prevent invasive mycoses in acute lymphoblastic leukaemia
AU - Cornely, Oliver A.
AU - Leguay, Thibaut
AU - Maertens, Johan
AU - Vehreschild, Maria J. G. T.
AU - Anagnostopoulos, Achilles
AU - Castagnola, Carlo
AU - Verga, Luisa
AU - Rieger, Christina
AU - Kondakci, Mustafa
AU - Härter, Georg
AU - Duarte, Rafael F.
AU - Allione, Bernardino
AU - Cordonnier, Catherine
AU - Heussel, Claus Peter
AU - Morrissey, C. Orla
AU - Agrawal, Samir G.
AU - Donnelly, J. Peter
AU - Bresnik, Mark
AU - Hawkins, Michael J.
AU - Garner, Will
AU - Gökbuget, Nicola
AU - on behalf of the AmBiGuard Study Group
AU - on behalf of the AmBiGuard Study Group
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Objectives: To prevent invasive fungal disease (IFD) in adult patients undergoing remission-induction chemotherapy for newly diagnosed acute lymphoblastic leukaemia (ALL). Patients and methods: In a double-blind multicentre Phase 3 study, patients received prophylactic liposomal amphotericin B (L-AMB) at 5 mg/kg intravenously or placebo twice weekly in a 2:1 random allocation during remission-induction treatment. The primary endpoint was the development of proven or probable IFD. Secondary endpoints included those focused on the safety and tolerability of prophylactic L-AMB. Results: Three hundred and fifty-five patients from 86 centres in Europe and South America received at least one dose of L-AMB (n = 237) or placebo (n = 118). Rates of proven and probable IFD assessed independently were 7.9%(18/228) in the L-AMB group and 11.7%(13/111) in the placebo group (P = 0.24). Rates of possible IFD were 4.8% (11/228) in the L-AMB and 5.4% (6/111) in the placebo group (P = 0.82). The remission-induction phase was a median of 22 days for both groups. Overall mortality was similar between the groups: 7.2% (17/237) for L-AMB and 6.8% (8/118) for placebo (P = 1.00). Hypokalaemia and creatinine increase were significantly more frequent with L-AMB. Conclusions: The IFD rate among adult patients undergoing remission-induction chemotherapy for newly diagnosed ALL was 11.7%in the placebo group, andwas not significantly different in patients receiving L-AMB, suggesting that the L-AMB regimen studied is not effective as prophylaxis against IFD. The IFD rate appears higher than previously reported, warranting further investigation. Tolerability of L-AMB was what might be expected. Further studies are needed to determine the optimal antifungal strategy during remission-induction chemotherapy of ALL.
AB - Objectives: To prevent invasive fungal disease (IFD) in adult patients undergoing remission-induction chemotherapy for newly diagnosed acute lymphoblastic leukaemia (ALL). Patients and methods: In a double-blind multicentre Phase 3 study, patients received prophylactic liposomal amphotericin B (L-AMB) at 5 mg/kg intravenously or placebo twice weekly in a 2:1 random allocation during remission-induction treatment. The primary endpoint was the development of proven or probable IFD. Secondary endpoints included those focused on the safety and tolerability of prophylactic L-AMB. Results: Three hundred and fifty-five patients from 86 centres in Europe and South America received at least one dose of L-AMB (n = 237) or placebo (n = 118). Rates of proven and probable IFD assessed independently were 7.9%(18/228) in the L-AMB group and 11.7%(13/111) in the placebo group (P = 0.24). Rates of possible IFD were 4.8% (11/228) in the L-AMB and 5.4% (6/111) in the placebo group (P = 0.82). The remission-induction phase was a median of 22 days for both groups. Overall mortality was similar between the groups: 7.2% (17/237) for L-AMB and 6.8% (8/118) for placebo (P = 1.00). Hypokalaemia and creatinine increase were significantly more frequent with L-AMB. Conclusions: The IFD rate among adult patients undergoing remission-induction chemotherapy for newly diagnosed ALL was 11.7%in the placebo group, andwas not significantly different in patients receiving L-AMB, suggesting that the L-AMB regimen studied is not effective as prophylaxis against IFD. The IFD rate appears higher than previously reported, warranting further investigation. Tolerability of L-AMB was what might be expected. Further studies are needed to determine the optimal antifungal strategy during remission-induction chemotherapy of ALL.
UR - http://www.scopus.com/inward/record.url?scp=85027147520&partnerID=8YFLogxK
U2 - 10.1093/jac/dkx133
DO - 10.1093/jac/dkx133
M3 - Article
C2 - 28575414
AN - SCOPUS:85027147520
VL - 72
SP - 2359
EP - 2367
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 8
ER -