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.
Randomized comparison of liposomal amphotericin B versus placebo to prevent invasive mycoses in acute lymphoblastic leukaemia / Cornely, O. A.; Leguay, T.; Maertens, J.; Vehreschild, M. J. G. T.; Anagnostopoulos, A.; Castagnola, C.; Verga, L.; Rieger, C.; Kondakci, M.; Harter, G.; Duarte, R. F.; Allione, B.; Cordonnier, C.; Heussel, C. P.; Morrissey, C. O.; Agrawal, S. G.; Peter Donnelly, J.; Bresnik, M.; Hawkins, M. J.; Garner, W.; Gokbuget, N.; Jarchum, G.; Dictar, M.; Ramirez Borga, S.; Valledor, A.; Knoebl, P.; Greil, R.; Linkesch, W.; Sill, H.; De Prijck, B.; Sonet, A.; Theunissen, K.; Selleslag, D.; Vargas Schwarzbold, A.; Nucci, M. L. M.; Lopes de Castro Lobo, C.; Fogliatto, L.; Bonmati, C.; Turlure, P.; Herbrecht, R.; Thiebaut, A.; Michallet, M.; Leguay, T.; Egerer, G.; Silling, G.; Pfreundschuh, M.; Hasenkamp, J.; Kraemer, D. M.; Topp, M.; Heinz, W.; Junghanss, C.; Schaich, M. A.; Parmentier, S.; Roellig, C.; Beck, H. J.; Huttmann, A.; Mousset, S.; Duenzinger, U. N.; Schwartz, S.; Haerter, G.; Kondakci, M.; Ostermann, H.; Rieger, C.; Cornely, O. A.; Vehreschild, M. J. G. T.; Tsirigotis, P.; Matsouka, P.; Angelopoulou, M. K.; Karakantza, M.; Spyridonidis, A.; Anagnostopoulos, A.; Kolomansky, A.; Moses, A.; Horowitz, N.; Rahav, G.; Aversa, F.; Velardi, A.; Pagano, L.; Gentile, G.; Gobbi, M.; Luppi, M.; Nosari, A. M.; Rambaldi, A.; Candoni, A.; Marbello, L.; Rossi, G.; Pogliani, E.; Allione, B.; Castagnola, C.; Moreira, I.; Nunes, A.; Botelho de Sousa, A.; Rubio Tejero, A. I.; Vallejo, C.; Vazquez, L.; Besalduch Vidal, J.; Gomez-Garcia de Soria, V.; Jurado Chacon, M.; Gonzalez Campos, J.; Olavarria, E.; Barba, P.; de la Serna Torroba, J.; Duarte, R.; Heim, D.; Zimmerli, S.; Gerber, B.; Akova, M.; Bolaman, A. Z.; Tabak, F.; Akan, H.; Senol, E.. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 0305-7453. - 72:8(2017), pp. 2359-2367. [10.1093/jac/dkx133]
Randomized comparison of liposomal amphotericin B versus placebo to prevent invasive mycoses in acute lymphoblastic leukaemia
Luppi M.;Candoni A.;
2017
Abstract
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.
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