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1238 Sequential Treatments in Chronic Phase Chronic Myeloid Leukemia (CML) Patients without Optimal Response after Frontline Nilotinib or Dasatinib: An Italian CML Campus StudyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster I
Hematology Disease Topics & Pathways:
Adult, Diseases, CML, Non-Biological, Therapies, Study Population, Myeloid Malignancies
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Gabriele Gugliotta, MD, PhD1, Mario Annunziata, MD2*, Isabella Capodanno, MD3*, Davide Rapezzi, MD4*, Immacolata Attolico, MD5*, Iolanda Donatella Vincelli6*, Mario Tiribelli, MD7*, Alessandra Malato, MD, PhD8*, Michele Pizzuti, MD9*, Vincenzo Accurso, MD10*, Massimiliano Bonifacio, MD11*, Sara Galimberti, MD, PhD12*, Giuseppina Loglisci, MD13*, Elisabetta Abruzzese, MD 14, Monica Bocchia15*, Antonella Gozzini, MD16*, Micaela Bergamaschi, MD17*, Maria Cristina Miggiano, MD18*, Agostino Tafuri, MD19, Grazia Sanpaolo, MD20*, Gianni Binotto, MD21*, Fausto Castagnetti, MD, PhD1, Giorgina Specchia, MD22, Francesco Di Raimondo, MD23, Michele Cavo1*, Gianantonio Rosti, MD1*, Robin Foà, MD24, Giuseppe Saglio, MD, PhD25, Massimo Breccia, MD26* and Fabio Stagno, MD, PhD23

1"Seràgnoli" Institute of Hematology, Sant'Orsola-Malpighi University Hospital, Bologna, Italy
2Hematology Unit, Cardarelli Hospital, Naples, Italy
3Hematology Unit, Azienda Unità Sanitaria Locale - IRCCS, Reggio Emilia, Italy
4S.C. Ematologia, ASO S. Croce e Carle, Cuneo, Italy
5Hematology and Stem cell Transplantation Unit - Department of Emergency and Organ Transplantation (D.E.T.O.) - University of Bari, Bari, Italy
6UOC Ematologia Grande Ospedale Metropolitano BMM, Reggio Calabria, Italy
7Division of Hematology and BMT, Department of Medical Area, University of Udine, Udine, Italy
8Department of Hematology, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
9Ematologia, Azieda Ospedaliera S. Carlo, Potenza, Italy
10U O di Ematologia Divisione di Oncologia, Az Osp Univ Policlinico P Giaccone Universita Studi Palermo, Palermo, Italy
11Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
12Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy
13Hematology Unit, Vito Fazzi Hospital, Lecce, Italy
14Hemoglobinopathies Unit, Hematology Department, S. Eugenio Hospital (ASL Roma 2), Tor Vergata University, Rome Italy, Rome, Italy
15Hematology, University of Siena, Siena, Italy
16Hematology Unit, AOU Careggi, University of Florence, Florence, ITA
17Hematology Clinic, Policlinico S.Martino-IRCCS, Genova, Italy
18Hematology Department, San Bortolo Hospital, Azienda ULSS8 "Berica" di Vicenza, Vicenza, Italy
19Hematology Unit, University Hospital Sant'Andrea-Sapienza, Rome, ITA
20Division of Hematology, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
21Department of Medicine, Hematology and Clinical Immunology, Padua School of Medicine, Padua, Italy
22Hematology Section, Department of Emergency and Transplantation - GIMEMA WP CML, University of Bari Aldo Moro, Bari, Italy
23Division of Hematology, A.O.U. "Policlinico-Vittorio Emanuele", University of Catania, Catania, Italy
24Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Policlinico Umberto I, Rome, Italy
25Divisione Universitaria di Ematologia e Terapie Cellulari, A.O. Ordine Mauriziano, Turin, Italy
26Department of Translational and Precision Medicine, Sapienza University, Rome, Italy

INTRODUCTION: Frontline therapy with second generation (2G) tyrosine-kinase inhibitors (TKIs) in chronic phase (CP) chronic myeloid leukemia (CML) patients demonstrated higher efficacy as compared to imatinib, with less patients experiencing treatment failure and progression to advanced disease. However, limited information are currently available on the management and outcome of those CML pts not achieving an optimal response to first-line treatment with a 2G-TKI.

AIM: To describe the clinical outcome of CP CML patients without an optimal response to a frontline 2G-TKI that switched to alternative TKIs.

METHODS: We performed a retrospective analysis in 22 Centers cooperating within the Italian CML Campus Project. Main inclusion criteria were: 1) diagnosis of CP-CML after 2010; 2) first-line treatment with a 2G-TKI; 3) switch to second-line treatment in case of non-optimal response (either following ELN recommendations or as for clinical practice); 4) CML in CP at the time of switching to second-line treatment. The main exclusion criteria were a switch to second-line treatment for intolerance or for low adherence to therapy.

RESULTS: The main findings of this analysis are summarized in the table. Seventy-one pts meeting the inclusion/exclusion criteria were identified; the median age of pts at CML diagnosis was 46 (21-80) years. Sokal risk score was low, intermediate, and high in 24 (34%), 30 (42%), and 17 (24%) pts, respectively. First-line treatment was performed with nilotinib in 47 (66%) pts and dasatinib in 24 (34%) pts. According to the ELN 2020 recommendations, 51 (72%) pts fulfilled the criteria for “failure” and 20 (28%) pts those for “warning”. BCR-ABL mutations were identified in 12 of 65 (18%) evaluable pts (T315I in 1 pt). Additional chromosomal abnormalities in Ph+ cells were identified in 6 of 54 (11%) evaluable pts.

Second-line treatment was started after a median time of 16 (4-72) months, with ponatinib (40 pts, 56%), dasatinib (21 pts, 30%), nilotinib (7 pts, 10%), or bosutinib (3 pts, 4%). Median follow-up from start of second-line treatment was 25 (2-90) months. Best response to second-line treatment was MR2 in 18 (25%) pts and MR3 in 37 (51%) pts.

Nineteen (27%) pts (13 for resistance and 6 for intolerance) switched to third-line treatment (ponatinib, 11 pts; nilotinib, 3 pts; dasatinib, 4 pts; imatinib, 1 pt), after a median time of 8 (1-72) months. Mutations were identified in 2 of 17 evaluable pts, and both patients harbored a T315I mutation. MR3 was reached by 9 (47%) of these pts. Lastly, 7 (10%) pts switched (6 for resistance and 1 for intolerance) to fourth-line treatment (asciminib, 4pts; dasatinib, 2 pts, nilotinib, 1 pt).

Overall, 44 (62%) patients reached with sequential TKI treatments a MR3 (31/51 pts among “failures”; 13/20 among “warnings”). Allogeneic stem-cell transplantation (SCT) was performed in 7 (9.5%) pts (6 among “failures”), after a median time of 20 (15-60) months from CML diagnosis. Progression to advanced phase occurred in 2 (3%) pts; both pts previously met the ELN2020 “failure” criteria. Estimated 4-y PFS was 92.5%. Death occurred in 3 (4%) pts (1 after progression to blast phase, 2 for cardiovascular adverse events). Estimated 4-y OS was 93.7%


Our findings show that CP-CML patients not achieving an optimal response to frontline 2G-TKI therapy, despite a complex management, still have a favorable prognosis and survival due to the availability of both multiple TKI options and SCT.

Disclosures: Gugliotta: Novartis: Honoraria; Incyte: Honoraria; Pfizer: Honoraria. Galimberti: Novartis: Speakers Bureau; Incyte: Honoraria. Abruzzese: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bocchia: CELGENE: Honoraria; Incyte: Honoraria. Castagnetti: Bristol Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Di Raimondo: Amgen, Takeda, Novartis: Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; GILEAD, Incyte: Research Funding; GSK: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Cavo: Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Rosti: Bristol-Myers Squibb: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau. Foà: Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Incyte: Speakers Bureau. Saglio: Pfizer: Research Funding; Ariad: Research Funding; Roche: Research Funding; Incyte: Research Funding; Bristol-Myers Squibb: Research Funding; Novartis: Research Funding. Breccia: Abbvie: Consultancy; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

*signifies non-member of ASH