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2891 Applicability of SIE/Sies/GITMO Fitness Criteria to Therapy-Related and AML-MRC Receiving CPX-351: Results from a Large, Retrospective, Multicentric, Observational Study

Program: Oral and Poster Abstracts
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, AML, adult, Research, elderly, Non-Biological therapies, Clinical Research, Chemotherapy, Diseases, real-world evidence, Therapies, Myeloid Malignancies, Study Population, Human
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Raffaele Palmieri, MD1*, Fabio Guolo, MD, PhD2,3*, Luana Fianchi, MD, PhD4*, Felicetto Ferrara, MD5*, Maria Paola Martelli, MD, PhD6*, Michela Rondoni7*, Capria Saveria8*, Paola Minetto, MD9, Clara Minotti10*, Sofia Sciabolacci11*, Federica Pilo, MD12*, Salvatore Perrone13*, Andrea Corbingi, MD14*, Francesco Grimaldi, MD15*, Giulia De Luca, MD16*, Carla Fili, MD17*, Caterina Alati, MD18*, Francesco Mannelli, MD19*, Federica Lessi, MD20*, Francesco Marchesi21*, Lorenzo Brunetti, MD22*, Debora Capelli, MD23*, Anna Lina Piccioni, MD24*, Calogero Vetro, MD25*, Carla Mazzone, MD26*, Alessandra Sperotto, MD27*, Giovanni Luzi28*, Michelina Dargenio, MD29*, Sabrina Mariani30*, Marco Cerrano, MD31*, Antonino Mulè, MD32*, Ambra Di Veroli, MD33*, Cristina Papayannidis, MD34, Alessandro Isidori, MD, PhD35, Francesco Lanza, MD36*, Michele Gottardi, MD27*, Elisabetta Todisco, MD37*, Livio Pagano, MD4*, Roberto Massimo Lemoli, MD3,38*, Francesco Buccisano, MD, PhD39 and Adriano Venditti, MD39

1Department of Onco-Hematology, Fondazione Policlinico Tor Vergata, Rome, Italy
2IRCCS Ospedale Policlinico San Martino, Genoa, Italy
3Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
4Dipartimento di Scienze Radiologiche Radioterapiche ed Ematologiche, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
5Divisione di Ematologia, Ospedale Cardarelli, Napoli, Italy
6Dipartimento di Medicina e Chirurgia, Hematology, Department of Medicine and Surgey, University of Perugia and "Santa Maria della Misericordia" Hospital, Perugia, ITA
7Hematology Unit & Metropolitan Transplant Network, Ravenna, AUSL Romagna, Ravenna, ITA
8Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy
9Clinica Ematologica, Dipartimento di Oncologia e Ematologia, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
10Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, ITA
11Hematology, Department of Medicine and Surgey, University of Perugia and "Santa Maria della Misericordia" Hospital, Perugia, Italy
12U.O.C. Ematologia e Trapianto di cellule staminali emopoietiche, A.O. Brotzu, Cagliari, ITA
13Hematology, Polo Universitario Pontino, "Sapienza", Via A. Canova S.M. Goretti Hospital, Latina, Italy
14Hematology, Polo Universitario Pontino, "Sapienza", S.M. Goretti Hospital, Latina, Italy
15Department of Clinical Medicine and Surgery, Hematology Unit, University of Naples Federico II, Naples, ITA
16UOC Ematologia Clinica, Ospedale Civile "Santo Spirito", Pescara, Italy
17Division of Hematology and Stem Cell Transplantation, University Hospital ASUF, Udine, Italy
18U.O.C. Ematologia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio Calabria, Italy
19Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
20Divisione di Ematologia e Centro Trapianti, Azienda Ospedaliera Universitaria di Padova, Padova, Italy
21Hematology Unit, IRCCS Regina Elena National Cancer Institute, Istituti Fisioterapici Ospitalieri (I.F.O.), Rome, ITA
22Clinica di Ematologia, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
23Clinica di Ematologia, Azienda Ospedaliero-Universitaria delle Marche, Ospedali Riuniti di Ancona, Ancona, ITA
24Dipartimento di Ematologia, Azienda Ospedaliera San Giovanni Addolorata, Rome, Italy
25Division of hematology, A.O.U. Policlinico G.Rodolico – S. Marco, Catania, Italy
26Hematology and Stem Cell Transplant Unit, St. Eugenio Hospital, Rome, ITA
27Onco Hematology, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Castelfranco Veneto, Italy
28Hematology and Stem Cell Transplant, San Camillo Forlanini Hospital, Rome, ITA
29Divisione di Ematologia e Centro Trapianti, CSE Vito Lazzi, Lecce, Italy
30Hematology Unit, Azienda Ospedaliera Universitaria Sant'Andrea, Sapienza University, Rome, ITA
31Division of Hematology, Department of Oncology, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy
32UOC di Oncoematologia,, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
33Hematology, Belcolle Hospital, Viterbo, Italy
34Istituto di Ematologia "Seràgnoli", IRCCS Azienda Ospedaliero–Universitaria di Bologna, Bologna, Italy
35Hematology and Stem Cell Transplant Center, AORMN Hospital, Pesaro, Italy
36Hematology Unit and Metropolitan Romagna Transplant Network, University of Bologna, Ravenna, Italy
37Hematology Department, ASST Valle Olona, Varese, Italy
38Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Italy, Genoa, Italy
39Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy


Treatment of therapy-related AML (t-AML) and AML evolving from an antecedent myelodysplastic syndrome (AML-MRC) represent a clinical unmet need being characterized by an unfavorable outcome. Among the emerging treatment options, CPX-351 has been approved by Regulatory Authorities for the treatment of fit patients (pts) affected by these AML sub-types. Although patented for the treatment of pts fit for intensive chemotherapy, in real-life CPX-351 is also administered to unfit ones, raising the case of tolerability in these categories. Among scores for fitness definition, SIE/SIES/GITMO criteria were extensively validated in large cohorts of AML pts receiving intensive chemotherapy and are increasingly incorporated into clinical trials. However, since these criteria have not been tested yet in the subset of t-AML and AML-MRC, we investigated their applicability in these pts receiving CPX-351.


Patients classified as t-AML or MRC-AML according to WHO2016 classification receiving at least one cycle of CPX-351 were included in the present analysis. Genetic and cytogenetic data were classified according to ELN2017 risk stratification. SIE/SIES/GITMO criteria were retrospectively applied to the whole series to categorize pts as fit or unfit to intensive chemotherapy (Ferrara et. al, Leukemia 2013), aiming at evaluating early-death rate and overall survival (OS). We also verified if ELN2017 risk-stratification might provide further information about long-term outcome, independently of fitness assessment.


This retrospective study includes 398 pts with t-AML (19.3%) or AML-MRC (80.7%) enrolled from 29 Italian Institutions between 2018 and 2023. Median age was 65 years (range 32-79), with a slight male prevalence (56.8%).

According to SIE/SIES/GITMO criteria, 323 (81.2%) pts qualified as fit and 75 (18.8%) as unfit. Based on ELN2017 risk stratification, 17 (4.3%) pts were classified as favorable, 162 (40.7%) as intermediate, 217 (54.5%) as adverse risk. Only 2 (0.5%) pts were not classifiable due to incomplete genetic data. No differences were observed in terms of ELN2017 risk distribution among the fit and unfit groups. After first induction, 188 of 323 (58.2%) fit and 42 of 75 (56%) unfit pts achieved a complete remission (CR), for a total of 230 (57.8%) pts entering CR. From CPX-351 start, 18 and 55 deaths at 28 days and at 100 days occurred, respectively. Early death rate at these early timepoints statistically differed between the two groups (3% vs. 10.7% at 28 days and 10% vs. 28% at 100 days for fit and unfit pts respectively; p<0.05). No excess of mortality was observed for unfit patients at any timepoint after 100 days from first CPX-351 induction. Competitive risk analyses showed no differences in terms of early death by relapse between the two groups.

With a median follow up of 24 months, unfit pts were characterized by a significantly shorter OS as compared to fit ones (median OS of 8 months [CI 95%: 4.1-11.8] and of 18 months [CI 95%: 14.7-21.1] for unfit and fit pts, respectively; p<0.0001) [Figure 1]. When stratified according to genetic/cytogenetic, median OS of fit pts was commensurate with ELN2017 risk (median OS not reached vs 20 months vs 13 months for favorable vs intermediate vs adverse risk, respectively; p < 0.01), whereas no differences in median OS were observed between favorable, intermediate, and adverse categories in unfit pts (median OS of 20 months vs 11 months vs 7 months, respectively; p=NS).


In our real-life analysis, we demonstrated that fitness assessment according to SIE/SIES/GITMO criteria identifies populations with discrete outcome among t-AML and AML-MRC pts receiving CPX-351. In unfit patients, outcome prediction seems independent from ELN 2017 risk stratification. Fit and unfit groups achieved similar CR rates but different long-term OS. Such discrepancy can be justified by the higher early mortality observed among unfit pts that translated into shorter long-term survival. In a future perspective, modulating CPX-351 schedule in this group may be a reasonable option to spare toxicity without giving up the opportunity to deliver curative-intended therapies.

Disclosures: Palmieri: Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Fianchi: Jazz Pharmaceuticals, Inc.: Honoraria; Sanofi: Honoraria; Bristol-Myers Squibb: Honoraria. Ferrara: ABBVIE: Honoraria. Martelli: Laboratoires Delbert: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Alati: Jazz: Honoraria; AbbVie: Honoraria. Vetro: Jazz Pharmaceuticals: Honoraria; BMS: Honoraria; ABBVIE: Honoraria. Cerrano: Insight Novartis Servier Abbvie Janssen Jazz Astellas Italfarmaco: Honoraria. Mulè: Pfizer: Honoraria; Astellas: Honoraria; Incyte: Honoraria; ABBVIE: Honoraria. Papayannidis: Pfizer, Astellas, Janssen, GSK, Blueprint, Jazz Pharmaceuticals, Abbvie, Novartis, Delbert Laboratoires: Membership on an entity's Board of Directors or advisory committees; Abbvie, Astellas, Servier, Menarini/Stemline, BMS, Pfizer, Amgen, Janssen, Incyte, Novartis: Honoraria. Pagano: AstraZeneca: Honoraria; Moderna: Honoraria; Menarini: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Gilead: Honoraria; Janseen: Honoraria; Jazz: Honoraria. Buccisano: Abbvie: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Janssen & Cylag: Consultancy, Honoraria; Becton Dickinson: Research Funding; Astellas: Consultancy, Honoraria. Venditti: Janssen: Consultancy, Honoraria, Other: travel support ; Amgen: Consultancy, Honoraria, Other: travel support ; Pfizer: Consultancy, Honoraria, Other: travel support , Speakers Bureau; Jazz: Consultancy, Honoraria, Other: travel support ; AbbVie: Consultancy, Honoraria, Other: travel support ; Medac: Consultancy; Novartis: Consultancy, Honoraria, Other: travel support .

*signifies non-member of ASH