Randomized comparison of liposomal amphotericin B versus placebo to prevent invasive mycoses in acute lymphoblastic leukaemia

• Published in: Journal of antimicrobial chemotherapy Vol. 72; no. 8; pp. 2359 - 2367
• Main Authors: Cornely, Oliver A, Leguay, Thibaut, Maertens, Johan, Vehreschild, Maria J G T, Anagnostopoulos, Achilles, Castagnola, Carlo, Verga, Luisa, Rieger, Christina, Kondakci, Mustafa, Härter, Georg, Duarte, Rafael F, Allione, Bernardino, Cordonnier, Catherine, Heussel, Claus Peter, Morrissey, C Orla, Agrawal, Samir G, Donnelly, J Peter, Bresnik, Mark, Hawkins, Michael J, Garner, Will, Gökbuget, Nicola
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-08-2017
• Subjects: Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B - administration & dosage; Antifungal Agents - administration & dosage; Chemoprevention - methods; Double-Blind Method; Europe; Female; Humans; Invasive Fungal Infections - prevention & control; Male; Middle Aged; Original Research; Placebos - administration & dosage; Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications; South America; Treatment Outcome; Young Adult
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkx133

To prevent invasive fungal disease (IFD) in adult patients undergoing remission-induction chemotherapy for newly diagnosed acute lymphoblastic leukaemia (ALL).
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.
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.
The IFD rate among adult patients undergoing remission-induction chemotherapy for newly diagnosed ALL was 11.7% in the placebo group, and was 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.