-Author name in bold denotes the presenting author
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731 Optimal Duration of CPX-351 Treatment and Best Timing for Consolidation with Allogeneic Stem Cell Transplantation: Evidence from a Large Real-World Italian Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Long-Term Outcomes for Children and Adults Diagnosed With AML/APL
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, AML, Biological therapies, Non-Biological therapies, Chemotherapy, Diseases, Therapies, therapy sequence, Myeloid Malignancies, Transplantation
Monday, December 11, 2023: 11:30 AM

Fabio Guolo, MD, PhD1,2*, Luana Fianchi, MD, PhD3*, Maria Paola Martelli, MD, PhD4*, Patrizia Chiusolo3*, Federico Lussana, MD, PhD5*, Francesco Grimaldi, MD6*, Federica Pilo, MD7*, Michela Rondoni8*, Carla Fili, MD9*, Debora Capelli, MD10*, Massimo Breccia11*, Sara Mastaglio, MD12*, Monica Bocchia, MD13*, Monica Fumagalli, MD14*, Sara Galimberti, MD, PhD15*, Valentina Mancini, MD16*, Anna Lina Piccioni, MD17*, Luca Maurillo, MD18*, Raffaele Palmieri, MD18*, Andrea Corbingi, MD19*, Calogero Vetro, MD20*, Alessandra Sperotto, MD21*, Federica Gigli, MD22*, Patrizia Zappasodi, MD23*, Antonio Mulé, MD24*, Erika Borlenghi, MD25*, Michelina Dargenio, MD26*, Federica Lessi, MD27*, Marco Cerrano, MD28*, Alessandro Isidori, MD, PhD29, Lorenzo Brunetti, MD30*, Cristina Papayannidis, MD31, Monia Lunghi, MD, PhD32*, Caterina Alati, MD33*, Samuele Gatani34*, Francesco Mannelli, MD35*, Nicola Fracchiolla, MD36*, Michele Gottardi, MD21*, Roberto Cairoli, MD37*, Felicetto Ferrara, MD38*, Roberto Massimo Lemoli, MD39,40*, Adriano Venditti, MD41, Livio Pagano, MD3* and Elisabetta Todisco, MD34*

1IRCCS Ospedale Policlinico San Martino, Genoa, Italy
2Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
3Dipartimento di Scienze Radiologiche Radioterapiche ed Ematologiche, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
4Dipartimento di Medicina e Chirurgia, Hematology, Department of Medicine and Surgey, University of Perugia and "Santa Maria della Misericordia" Hospital, Perugia, ITA
5Department of Oncology-Hematology, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
6Department of Clinical Medicine and Surgery, Hematology Unit, University of Naples Federico II, Naples, ITA
7SC di Ematologia e CTMO,, Ospedale Oncologico di Riferimento Regionale "A. Businco", ARNAS "G. Brotzu", Cagliari, Italy
8Hematology Unit & Metropolitan Transplant Network, AUSL Romagna, Ravenna, Italy
9Division of Hematology and Stem Cell Transplantation, University Hospital ASUF, Udine, Italy
10Clinica di Ematologia, Azienda Ospedaliero-Universitaria delle Marche, Ospedali Riuniti di Ancona, Ancona, ITA
11Department of Translational and Precision Medicine, Hematology-Sapienza University, Rome, Italy
12Hematology and Bone Marrow Transplant, Unit San Raffaele Scientific Institute, Milan, Italy
13UOC Ematologia, Azienda ospedaliero-universitaria Senese, Siena, Italy
14Hematology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
15Department of Clinical and Experimental Medicine, Hematology, University of Pisa, Pisa, Italy
16Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
17Dipartimento di Ematologia, Azienda Ospedaliera San Giovanni Addolorata, Rome, Italy
18Department of Onco-Hematology, Fondazione Policlinico Tor Vergata, Rome, Italy
19Hematology, Polo Universitario Pontino, "Sapienza", S.M. Goretti Hospital, Latina, Italy
20Division of hematology, A.O.U. Policlinico G.Rodolico – S. Marco, Catania, Italy
21Onco Hematology, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Castelfranco Veneto, Italy
22Divisione di Oncoematologia, European Institute of Oncology, Milan, Italy
23Clinica Ematologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
24Division of Hematology 1, Azienda Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
25Hematology, ASST Spedali Civili, Brescia, Italy
26Divisione di Ematologia e Centro Trapianti, CSE Vito Lazzi, Lecce, Italy
27Divisione di Ematologia e Centro Trapianti, Azienda Ospedaliera Universitaria di Padova, Padova, Italy
28Division of Hematology, Department of Oncology, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy
29Hematology and Stem Cell Transplant Center, AORMN Hospital, Pesaro, Italy
30Clinica di Ematologia, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
31Istituto di Ematologia "Seràgnoli", IRCCS Azienda Ospedaliero–Universitaria di Bologna, Bologna, Italy
32Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
33U.O.C. Ematologia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio Calabria, Italy
34Hematology Department, ASST Valle Olona, Varese, Italy
35CRIMM, Center for Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
36Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milano, Italy
37Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
38Divisione di Ematologia, Ospedale Cardarelli, Napoli, Italy
39Clinic of Hematology, Department of Internal medicine (DiMI), University of Genoa, Genoa, Italy
40Clinica Ematologica, Dipartimento di Oncologia e Ematologia, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
41Department of Onco-Hematology, Fondazione Policlinico Tor Vergata, Rome, Italy, Italy

Background: CPX-351, has been approved for the treatment of patients diagnosed with Acute Myeloid Leukemia (AML) arising from a previous myelodysplastic syndrome (s-AML) or secondary to chemotherapy (t-AML) as per former WHO 2016 classification, following results from the phase III trial (Lancet et al, JCO2018). Long term results from the trial confirmed that the benefit from CPX-351 over conventional 3+7 induction was maintained both in patients proceeding or not to allogeneic stem cell transplantation consolidation (HSCT). However, the information on the optimal duration of treatment with CPX-351 or the best timing for HSCT consolidation are still incomplete. Furthermore, there is also scarce data on the efficacy of CPX-351 among NPM1 or FLT3-ITD mutated AML or in patient with low risk AML according to European Leukemia Net (ELN) classification, as those subgroups are rare among t-AML and s-AML.

Aims: The aim of this study is to analyze the outcome of CPX-351 treatment in a large cohort of patient who received commercially available treatment in Italy since the approval of the drug, in order to identify the optimal duration of treatment, the best timing for HSCT and to evaluate the efficacy among more rare secondary AML subtypes.

Methods: 513 elderly (median age 65.6 years, range 19-79) s-AML or t-AML patients who received CPX-351 treatment in 38 Italian Centers since January 2019 were retrospectively included in this study. All patients received CPX-351 as per Italian Drug Authority (AIFA) approval, allowing up to two induction cycles and up to two consolidation. Diagnostic workup was performed as per internal standard in all patients. Eligible patients proceeded to HSCT consolidation as per internal standard of each Center. 108 (21.1%) and 405 (78.9%) patients were diagnosed with t-AML or s-AML, respectively. NPM1 mutation were found in 31 patients (6%), FLT3-ITD mutation was present in 24 patients (4.6%). ELN 2017 score was favorable, intermediate or high in 27 (5.2%), 177 (34.5%) and 309 (60.3%) patients, respectively. Most patients had relevant comorbidities (84%), mainly cardiovascular disease (43%), type II diabetes (39%).

After induction 1, 297/513 patients (58%) achieved a complete remission (CR). 72 patients failing to achieve CR received induction 2. After induction 2, CR was achieved in 340/513 patients (66.3%). CR rate was significantly higher among NPM1 mutated patients (p <0.05) and among ELN 2017 favorable risk patients if compared to intermediate or high risk (p<0.05), whereas was not affected by FLT3-ITD mutations. Among responding patients, 118 (34.7%), 137 (40.3%) and 85 (25%) received none, one or two consolidation cycles, respectively. HSCT consolidation in first CR was performed in 166/340 responding patients (48.8%). 30 and 60-days mortality were 5.2 and 8.2%, respectively.

After a median follow-up of 23.66 months (CI 95% 23.11 – 26.01), median OS was 16.23 months (CI 95% 13.6 – 18.9).

OS was significantly influenced by NPM1 mutational status (p<0.05) and ELN 2017 risk score (p<0.05, Fig. 1A). Of note, NPM1 mutated patients and ELN 2017 low-risk patients showed a very good outcome (Median OS 24.6 months for NPM1 mutated patients and not reached in ELN 2017 favorable risk patients).

In a landmark analysis including patients alive and in CR at day 90, HSCT was the strongest predictor of longer survival (Median OS not reached and 16.3 months for patients receiving or not HSCT, respectively, p<0.05). In the same landmark model, completion of all allowed CPX-351 treatment was beneficial only in patients not proceeding to HSCT (median OS 20.36 and 12.2 months in patients receiving 2 or less CPX-351 consolidation without HSCT, respectively, p<0.05, Fig. 1B), whereas in patients receiving HSCT consolidation further CPX-351 treatment after cycle 1 did not improve results (Median OS not reached, 35 and 28.4 months in HSCT patients receiving 0, 1 or 2 CPX-351 consolidations, respectively, p=n.s.)

Conclusions: Our large cohort confirms the efficacy of CPX-351 treatment and suggests that CPX-351 may be beneficial also in NPM1 mutated and ELN 2017 favorable risk patients. In eligible patients, HSCT should probably be performed as soon as a CR is achieved, whereas patients not proceeding to HSCT may still have a long survival if two consolidations are administered. In a future perspective, maintenance strategies may further improve the results.

Disclosures: 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: Janseen: Honoraria; Pfizer: Honoraria; Gilead: Honoraria; Jazz: Honoraria; Novartis: Honoraria; Menarini: Honoraria; Moderna: Honoraria; AstraZeneca: Honoraria.

*signifies non-member of ASH