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Clinical Trial
. 2025 Dec;100(12):2293-2304.
doi: 10.1002/ajh.70083. Epub 2025 Sep 24.

Real World Study on the Best CPX-351 Treatment Duration and Timing for Allogeneic Stem Cell Transplantation

Fabio Guolo  1   2 , Luana Fianchi  3 , Maria Paola Martelli  4 , Federico Lussana  5 , Francesco Grimaldi  6 , Federica Pilo  7 , Michela Rondoni  8 , Carla Filì  9 , Paola Minetto  2 , Debora Capelli  10 , Patrizia Chiusolo  11 , Massimo Breccia  12 , Sara Mastaglio  13 , Massimo Bernardi  13 , Monica Bocchia  14 , Monica Fumagalli  15 , Sara Galimberti  16 , Valentina Mancini  17 , Anna Lisa Piccioni  18 , Luca Maurillo  19 , Nicola Stefano Fracchiolla  20 , Raffaele Palmieri  19 , Calogero Vetro  21 , Cristina Papayannidis  22 , Lorenzo Brunetti  10 , Alessandra Sperotto  23 , Federica Gigli  24 , Patrizia Zappasodi  25 , Antonino Mulé  26 , Caterina Patti  26 , Erika Borlenghi  27 , Michelina Dargenio  28 , Federica Lessi  29 , Marco Cerrano  30 , Daniela Cilloni  31 , Alessandro Isidori  32 , Monia Lunghi  33 , Caterina Alati  34 , Carmela Gurrieri  29 , Carola Riva  1 , Giovanni Marconi  8 , Ivana Lotesoriere  35 , Samuele Gatani  35 , Anna Maria Scattolin  36 , Manuela Caizzi  37 , Salvatore Perrone  38 , Atto Billio  39 , Filippo Gherlinzoni  40 , Francesco Mannelli  41 , Michele Gottardi  23 , Roberto Cairoli  17 , Anna Candoni  42 , Felicetto Ferrara  43 , Livio Pagano  3 , Roberto Massimo Lemoli  1   2 , Adriano Venditti  19 , Elisabetta Todisco  35
Affiliations
Clinical Trial

Real World Study on the Best CPX-351 Treatment Duration and Timing for Allogeneic Stem Cell Transplantation

Fabio Guolo et al. Am J Hematol. 2025 Dec.

Abstract

In the registration clinical trial 301 (NCT01696084), CPX-351 has shown to be superior to conventional 3 + 7 in secondary AML (s-AML). However, the optimal duration of treatment, the best timing for allogeneic stem cell transplantation (allo-HSCT), and the activity of CPX-351 in specific s-AML subgroups are unclear. To evaluate these aspects, a total of 513 s-AML patients (median age 65.6 years, 19-79) treated with CPX-351 were retrospectively analyzed. Complete remission (CR) rate after induction was 297/513 (58%), increasing to 340/513 (66%) after cycle 2. Among the 340 responding patients, 118 (34.7%), 137 (40.3%), and 85 (25%) received none, one, or two consolidation cycles of CPX-351, respectively. Overall, 230/513 patients (48.8%) received allo-HSCT. Median follow up was 23.66 months and median overall survival (OS) was 16.23 months. Patients with mutated NPM1 or with ELN 2017 favorable risk (p < 0.05) had a significantly longer OS (p < 0.05). In a landmark analysis, receiving allo-HSCT was associated with a longer survival (Median OS not reached vs. 16.3 months for patients receiving or not receiving allo-HSCT, p < 0.05). Completion of all allowed CPX-351 cycles was beneficial only in patients not proceeding to transplant (p < 0.05), whereas in transplanted patients additional CPX-351 cycles did not improve outcome. Our analysis suggests that also s-AML patients with NPM1 mutations and those belonging to the ELN 2017 favorable risk category benefit from CPX-351. In eligible patients, allo-HSCT should be performed as soon as a CR is achieved, whereas patients not undergoing transplant benefit from a complete CPX-351 schedule.

Keywords: CPX‐351; acute myeloid leukemia; allogeneic stem cell transplantation; drug optimization.

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Conflict of interest statement

Guolo: Jazz Pharmaceuticals Inc.: Consultancy; Fianchi: Jazz Pharmaceuticals Inc.: Honoraria; Sanofi: Honoraria; Bristol‐Myers Squibb: Honoraria. Martelli: AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Laboratoires Delbert: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria. Lussana: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Speakers Bureau; Clinigen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau. Breccia: Incyte: Honoraria; AbbVie: Honoraria; Novartis: Honoraria; AOP: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Bocchia: Novartis: Honoraria; Incyte: Honoraria; BMS: Honoraria. Galimberti: AbbVie, Janssen, Novartis, Roche, Jazz, Astra Zeneca, Pfizer, Incyte: Speakers Bureau. Palmieri: Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Vetro: Jazz Pharmaceuticals: Honoraria; BMS: Honoraria; ABBVIE: Honoraria. Zappasodi: Amgen, Pfizer, AbbVie, Astellas: Honoraria. Borlenghi: AbbVie, BMS: Consultancy; Amgen, Incyte: Other: travel grants. Cerrano: Insight Novartis Servier AbbVie Janssen Jazz Astellas Italfarmaco: Honoraria. Papayannidis: AbbVie, Astellas, Servier, Menarini/Stemline, BMS, Pfizer, Amgen, Janssen, Incyte, Novartis: Honoraria; Pfizer, Astellas, Janssen, GSK, Blueprint, Jazz Pharmaceuticals, AbbVie, Novartis, Delbert Laboratoires: Membership on an entity's Board of Directors or advisory committees. Alati: AbbVie: Honoraria; Jazz: Honoraria. Fracchiolla: AbbVie, Jazz, Pfizer, Amgen: Other: travel grants; AbbVie, Jazz, Pfizer, Amgen: Speakers Bureau. Ferrara: ABBVIE: Honoraria. Venditti: Medac: Consultancy; Janssen: Consultancy, Honoraria, Other: travel support; AbbVie: Consultancy, Honoraria, Other: travel support; Jazz: Consultancy, Honoraria, Other: travel support; Amgen: Consultancy, Honoraria, Other: travel support; Pfizer: Consultancy, Honoraria, Other: travel support, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel support. Pagano: Janssen: Honoraria; Pfizer: Honoraria; Gilead: Honoraria; Jazz: Honoraria; Novartis: Honoraria; Menarini: Honoraria; Moderna: Honoraria; AstraZeneca: Honoraria. The Authors state that they have no other relevant conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Treatment outline. Figure 1 shows the detailed sequence of CPX‐351 treatment administered to the 513 patients in the study, as well as the timing for allogeneic stem cell transplantation. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
Overall survival according to transplant (landmark analysis). Figure 2 depicts the overall survival in a landmark analysis model of the 363 patients who achieved a morphological leukemia‐free status or a CR and were alive at day 90 (landmark) according to whether they received allogeneic stem cell transplantation consolidation, either in CR or in MLFS or did not receive transplant. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 3
FIGURE 3
Survival of patients submitted to transplant based on the number of CPX‐351 courses received. Figure 3 depicts the overall survival in a landmark analysis model of the 230 patients who were alive and at least in a morphological leukemia‐free status at day 90 and received an allogeneic stem cell transplantation according to the number of CPX‐351 cycles received before the transplant. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 4
FIGURE 4
Survival according to number of consolidations in non‐transplanted patients. Figure 4 depicts the overall survival in a landmark analysis model of the 133 patients who were alive and at least in a morphological leukemia‐free status at day 90 and did not receive an allogeneic stem cell transplantation, according to the total number of CPX‐351 consolidation cycles received. [Color figure can be viewed at wileyonlinelibrary.com]
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