Real-World Efficacy Profile of Compassionate Use of Asciminib in an Italian, Multi-Resistant Chronic-Phase Chronic Myeloid Leukemia (CML-CP) Patient Population.

Silvia Sibilla, Antonella Gozzini, Monica Crugnola, Felicetto Ferrara, Carmen Fava, Anna Ermacora, Luciano Levato, Mario Annunziata, Bruno Martino, Massimo Breccia, Ambra Di Veroli, Alessandra Misto, Fausto Castagnetti, Valeria Calafiore, Maria Cristina Carraro, Federica Cattina, Lara Crucitti, Paolo Ditonno, Angelo Genua, Stefana Impera, Maria Cristina Miggiano, Serena Rosati, Teresa Maria Santeramo, Sabina Russo, Francesco Cavazzini, Antonella Russo Rossi, Elisabetta Abruzzese, Luigia Luciano, Barbara Scappini, Marco De Gobbi, Federica Sorà, Maria Teresa Corsetti, Paola Coco, Rosaria Sancetta, Marco Santoro, Claudia Baratè, Aurelio Pio Nardozza, Paolo Sportoletti, Andrea Patriarca, Valentina Giai, Grazia Sanpaolo, Anna Rita Scortechini, Fabio Stagno, Elena Trabacchi, Gianni Binotto, Alessandra Iurlo

Journal: Hematological oncology 2025;43(3):e70101

PMID: 40344674

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Abstract

Chronic myeloid leukemia (CML) patients who have experienced failure and/or intolerance to multiple lines of treatment have limited therapeutic possibilities. Asciminib is a first-in-class tyrosine kinase inhibitor (TKI) that inhibits the ABL Myristoyl Pocket (STAMP or Specifically Targeting the ABL Myristoyl Pocket) within the BCR::ABL1 oncoprotein. This retrospective Italian analysis reports the efficacy and safety outcomes of asciminib in treating 77 CML patients in chronic phase (CML-CP) within a compassionate use setting. Patients were heavily pretreated with a median of 3 TKIs (55.8% had prior ponatinib exposure). Overall, 57.1% and 42.9% patients switched to asciminib because of resistance and intolerance, respectively. Asciminib maintained or improved molecular responses (MRs) in most patients: as best response, 41 patients (53%) achieved a MR3 or better, with 25 patients (32.5%) reaching deep molecular response (DMR). Greater percentages of intolerant patients achieved MR compared with resistant patients, although the probability of reaching at least a MR3 was not significant between the two groups (p = 0.116). Patients with the T315I mutation responded to asciminib, while ponatinib pre-treated patients showed lower MR improvements compared to naïve patients and had a lower probability to reach a MR3 versus naïve patients (p = 0.0262). These results highlight asciminib remarkable tolerability and efficacy in real-world CML-CP patient population, including heavily pretreated patients, those intolerant and resistant to previous TKIs, and presenting several comorbidities. TRAIL REGISTRATION: The identification code for the MAP is CABL001AIT01M.

Address: Division of Hematology, Department of Translational and Precision Medicine, Azienda Policlinico Umberto I, Sapienza University, Rome, Italy.; Hematology and Transplantation Unit, University of Bari, Bari, Italy.; Division of Haematology, A.O.U. Città della Salute e della Scienza, Turin, Italy.; Division of Hematology, Azienda Ospedaliera "Bianchi Melacrino Morelli", Reggio Calabria, Italy.; Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.; Hematology Unit, Cardarelli Hospital, Napoli, Italy.; Hematology Unit, S. Eugenio Hospital, ASL Roma2, Tor Vergata University, Rome, Italy.; Department of Medicine, Unit of Hematology and Clinical Immunology, University of Padova, Padova, Italy.; Department of Clinical and Experimental Medicine, UO Hematology, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.; Medical Department, Novartis, Novartis Farma SpA, Milan, Italy.; U.O. Oncoematologia, A.O.R. Villa Sofia - Vincenzo Cervello, Palermo, Italy.; UOC Hematology and Transfusion Medicine, Ospedale Luigi Sacco, Milan, Italy.; Oncology Unit, Hospital Crema, Crema, Italy.; Hematology Unit, University of Ferrara, Ferrara, Italy.; Hematology Division, Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.; Unità Operativa Ematologia, Azienda Sanitaria Provinciale Trapani, Presidio Ospedaliero Castelvetrano, Trapani, Italy.; Hematology Unit and BMT Center University Hospital of Parma, Parma, Italy.; Hematology, Belcolle Hospital, Viterbo, Italy.; Haematology Unit, National Cancer Center, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.; Haematology Unit, Azienda Ospedaliera S. Maria Angeli, Pordenone, Italy.; UOC Ematologia, AORN "A. Cardarelli", Napoli, Italy.; Hematology Unit, Azienda Ospedaliera Santa Maria di Terni, Terni, Italy.; Department of Cellular Therapies and Transfusion Medicine, AOU Careggi, Florence, Italy.; Division of Oncology and Hematology, ARNAS Garibaldi-Nesima, Catania, Italy.; Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department Hematology-Oncology, Azienda Ospedaliera Universitaria "Renato Dulbecco", Catanzaro, Italy.; Hematology Unit, Federico II University of Naples, Naples, Italy.; Hematology Department, San Bortolo Hospital, Vicenza, Italy.; Department of Clinical and Biological Sciences, Internal Medicine With Hematological Focus, AOU San Luigi, University of Turin, Turin, Italy.; UO Hematology, University Hospital Paolo Giaccone, Palermo, Italy.; Hematology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.; Hematology Unit, Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona, Ancona, Italy.; Department of Translational Medicine, Hematology Unit, University of Eastern Piedmont and AOU Maggiore della Carità, Novara, Italy.; Ospedale Nuovo Santo Stefano, Prato, Italy.; Dipartimento di Patologia Umana dell'Adulto e dell'Età Evolutiva, Division of Hematology, Policlinico G. Martino, University of Messina, Messina, Italy.; Hematology Unit, ULSS 3, Dell'Angelo Hospital, Venezia-Mestre, Italy.; Department of Hematology and Stem Cell Transplantation Unit, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.; Hematology Unit, Dimiccoli Hospital, Barletta, Italy.; UO di Ematologia e trapianto, Azienda Ospedaliera Cardinale G. Panico, Tricase, Italy.; Dipartimento di Scienze di laboratorio ed ematologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.; Dipartimento di Scienze Radiologiche ed Ematologiche, Sezione di Ematologia, Università Cattolica del Sacro Cuore, Rome, Italy.; Centro Ricerche Emato-Oncologiche, Institute of Hematology, Ospedale S. Maria della Misericordia, University of Perugia, Perugia, Italy.; Hematology Unit, AOU Policlinico "G. Martino", University of Messina, Messina, Italy.; Hematology Unit and BMT Center, Ospedale G. Saliceto, Piacenza, Italy.; Institute of Hematology "Seràgnoli" IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

DOI: 10.1002/hon.70101