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1778 Treatment-Free Remission in CML Patients Discontinuing Post-First Line Therapy

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Treatment Considerations
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Selene Grano, MD1*, Valentina Bonuomo, MD2*, Emanuele Koumantakis, MD3*, Paola Berchialla, PhD4*, Fausto Castagnetti, MD, PhD5,6, Massimo Martino, MD7*, Chiara Elena, MD8*, Monica Bocchia, MD9*, Isabella Capodanno, MD10*, Tamara Intermesoli11*, Maria Cristina Miggiano12*, Carlo Gambacorti-Passerini, MD, Prof.13, Alessandra Iurlo, MD, PhD14*, Francesca Lunghi15*, Luigiana Luciano, MD16, Elisabetta Abruzzese, MD17, Angelo Michele Carella, MD18*, Massimo Breccia19*, Felicetto Ferrara, MD20*, Sabrina Leonetti Crescenzi, MD21*, Barbara Scappini22*, Marco De Gobbi, MD, PhD23*, Federica Sorà24*, Davide Rapezzi, MD25*, Debora Luzi, MD26*, Sara Galimberti, MD27*, Monica Crugnola, MD28*, Anna Rita Scortechini, MD29*, Alessandro Maggi30*, Massimiliano Bonifacio, MD31*, Mario Annunziata, MD32*, Giovanni Caocci, MD33, Germana Beltrami, MD34*, Francesco Cavazzini, MD35*, Giuseppe Pietrantuono, MD36*, Leonardo Campiotti37*, Fabio Stagno, MD, PhD38, Caterina Musolino39* and Carmen Fava, MD, PhD40*

1Department of Molecular Biotechologies and Health Sciences, University of Torino, Turin, ITA
2Department of Clinical and Biological Sciences, University of Turin, Torino, Italy
3Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università degli Studi di Torino, Torino, Italy
4Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy
5Department of Medical and Surgical Sciences, Institute of Hematology “Seràgnoli”, University of Bologna, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
6Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
7Centro Unico Trapianti A, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio Calabria, Italy
8U.O.C Ematologia 1, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
9Hematology Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Siena, Italy
10hematology, AUSL Reggio Emilia, Reggio Emilia, Italy
11Hematology and Bone Marrow Transplant Unit, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
12Hematology Department, San Bortolo Hospital, Vicenza U.O.C. di Ematologia, Vicenza, ITA
13Department of Medicine and Surgery, University Milano-Bicocca, Monza, Italy
14Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
15San Raffaele Institute Milano Italy, Milano, ITA
16Hematology Unit, Federico II University, Napoli, Italy
17Department of Hematology S. Eugenio Hospital, Rome, Italy, Roma, Italy
18Hematology and Bone Marrow Transplant Unit, IRCCS Fondazione Casa Sollievo della Sofferenza San Giovanni Rotondo, Foggia, Italy, San Giovanni Rotondo, Italy
19Department of Translational and Precision Medicine, Az., Hematology-Sapienza University, Rome, Italy
20Division of Hematology, AORN Cardarelli, Naples, Napoli, Italy
21Division of Hematology, Azienda Ospedaliera San Giovanni Addolorata, Roma, Italy
22Hematology Unit, Hematology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
23Department of Clinical and Biological Sciences, Department of Clinical and Biological Sciences, University of Turin, Orbassano, ITA
24Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
25Department of Hematology, S. Croce e Carle Hospital, Cuneo, Italy
26Onco-Hematology Department, AO Santa Maria, Terni, Terni, Italy
27Department of Clinical and Experimental Medicine, Hematology, University of Pisa, Pisa, Italy
28Hematology Unit and BMT Center Azienda Ospedaliero Universitaria Parma, Parma, Italy
29Division of Hematology, Department of Molecular and Clinical Sciences, University of Marche, Ancona, Italy, Ancona, Italy
30Haematology division, Ospedale S.G. Moscati, Taranto, Italy
31Department of Engineering for Innovation Medicine, Section of Innovation Biomedicine, Hematology Area, University of Verona, Verona, Italy
32Hematology, San Giuseppe Moscati Hospital, Aversa, Italy
33Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
34U.O. Ematologia e terapie cellulari, IRCCS Azienda Ospedaliera Universitaria San Martino, Genova, Italy
35Division of Hematology, Arcispedale Sant'Anna, University of Ferrara, Ferrara, ITA
36Hematology and Stem Cell Transplantation Unit, IRCCS Centro Oncologico della Basilicata, Rionero in Vulture, Italy
37Department of Medicine and Surgery, University of Insubria, Varese, ITA
38Division of Hematology, AOU Policlinico “G. Martino”, University of Messina, Italy, Catania, Italy
39Division of Hematology, Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, Italy
40Department of Clinical and Biological Sciences, University of Turin, Torino, Italy, Orbassano, To, Italy

Background: Recommendations for treatment discontinuation in patients with Ph+ Chronic Myeloid Leukemia (CML) stipulate that it should be proposed in the first line of Tyrosine Kinase Inhibitors (TKIs) treatment or in the second line if the reason for change was intolerance. There are reports in literature of patients (pts) who discontinued therapy in second line also for resistance, with outcome comparable or inferior to those with intolerance depending on the studies.

Aims: This study aims to identify prognostic factors for maintaining response in the context of post-first line suspensions. We proposed a focused sub-analysis within the context of the Italy-TFR observational study (NCT04769947) which is ongoing and currently includes 673 pts.

Methods: We performed descriptive statistics and survival analysis with Kaplan-Meier. Bayesian Model Averaging (BMA) was used to assess potential risk factors. BMA averages all data-supported models to estimate effect sizes of variables on the endpoint. The percentage of inclusion (PI) indicates how often a variable appears across models, suggesting its importance. Standard rules of thumb for interpreting this posterior probability are: P<50% evidence against the effect; 50-75% weak evidence; 75-95% positive evidence; >95% strong evidence.

Results: We collected the data from 144 pts who attempted TFR in second or later lines of treatment with switch due to resistance (33) or intolerance (53) or unknown reason (58). Median age at discontinuation was 64 years (IQR 53-74); 49% of pts were male. Among resistant pts the majority discontinued a 2nd generation TKI, 1 discontinued ponatinib and 1 discontinued imatinib. This pattern was similar to what we observed in intolerant pts. First line treatment in resistant and intolerant pts was imatinib in 87% of pts. Median duration of total treatment was 110 months (IQR 80-147). In the resistant group, 43.8% of pts showed less than Complete Cytogenetic Response (CCyR) as best response to first line therapy, defined as low response, while 56.3% achieved a CCyR, a major molecular response (MMR) or deep molecular response (DMR), defined as high response; in the intolerant group 24.5% and 75.5% of pts had a low and high response, respectively (p<0.001). Thus, we stratified pts who discontinued in second or later lines by best response to first TKIs: Low Responders (LoRes, 31 pts) were resistant in 53.8% and intolerant in 46.2%, High Responders (HiRes, 65 pts) were resistant in 32.7% and intolerant in 67.3% (p 0.09); there was no significant difference in Sokal score. Combining HiRres, LoRes and resistant or intolerant, we distinguished 4 subgroups of pts, whom showed statistically significant differences in rates on Kaplan-Meier curves: at 24 month, 35% of resistant-LoRes maintained TFR vs 71% of resistant-HiRes, vs 82% of intolerant-LoRes, vs 92% of intolerant-HiRes. (p<0.001). Using BMA, longer duration of the last TKI (PI=69%), better response to prior treatment (PI=40%), better response at 3 months (PI=40%), and longer DMR duration from first treatment start (PI=30%) emerged as the strongest factors associated with TFR persistence, whereas resistance to treatment (PI=55%) was associated to treatment restart. Resistant compared to intolerant had an increased risk to restart treatment (HR=4.94, P=91%). Among intolerant pts, each additional month of TKI treatment was associated with a risk reduction of 4% (HR = 0.96, P=93%). The same effect was not observed among resistant pts (HR=1.04, P=84%). Pts with a response at 3 months that was at least MMR had a risk reduction of 63% (HR=0.37, P=91%).

Conclusions: We have shown that TFR may be feasible for some pts treated in second-line, not only for intolerance. Duration of TKI treatment seems to be the most relevant prognostic factor also in this category of pts. More observations are needed to safely include second line resistant pts in an elective discontinuation process.

Disclosures: Bocchia: Novartis: Honoraria, Other: travel grant; Incyte: Honoraria, Other: travel grant; Abbvie: Honoraria, Other: travel grants. Capodanno: BMS: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau. Iurlo: Incyte: Consultancy, Honoraria; AOP: Consultancy, Honoraria; BMS: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Abruzzese: MorphoSys: Consultancy; Ascentage: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Incyte: Consultancy; BMS: Consultancy. Breccia: Incyte: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Abbvie: Honoraria; BMS: Honoraria; AOP: Honoraria; GSK: Honoraria. Galimberti: Celgene: Honoraria; Roche: Honoraria, Other: support for attending meetings; Incyte: Honoraria; Novartis: Honoraria, Other: support for attending meetings; Jazz: Honoraria, Other: support for attending meetings; AstraZeneca: Honoraria, Other: support for attending meetings; AbbVie: Honoraria, Other: support for attending meetings; Pfizer: Honoraria; Janssen: Honoraria. Crugnola: Novartis: Speakers Bureau; BMS: Speakers Bureau. Bonifacio: Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Stagno: Novartis: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau.

*signifies non-member of ASH