Baseline Features, Treatment Choice and Early Frontline TKI Permanent Discontinuation in Patients with Newly Diagnosed Chronic Myeloid Leukemia Aged 50 - 60 Years: A “Campus CML” Study

Introduction: Median age at diagnosis in patients (pts) with Chronic Myeloid Leukemia (CML) is 58 - 60 years: while Second Generation Tyrosine-Kinase Inhibitors (2G-TKIs) are preferred in younger pts and imatinib (IMA) in elderly pts, there is no definite consensus on the best choice in middle-aged cases Aim: To analyze initial features, choice of frontline TKI and early adverse events leading to permanent TKI discontinuation in the first 12 months from TKI start in newly diagnosed subjects aged 50 - 60 in a large real-life cohort of CML pts Methods: Among 1967 CML pts newly diagnosed from 1/2012 to 12/2019 in 38 Italian Centers participating at the “Campus CML” project, 424 (21.5%) aged 50 - 60 years: their features at diagnosis and during the first year of TKI treatment were collected and analyzed in the present report Results: According to responsible physician choice, 191 pts (45.0%) received frontline IMA and 233 (55.0%) a 2G-TKI (dasatinib in 78, nilotinib in 135). Comparing the main clinical features at diagnosis according to frontline TKI, pts treated with 2G-TKI had higher WBC count (69.0 vs 48.8 x 109/l, p=0.002) and int/high-risk Sokal score (55.6 vs 42.2%, p=0.006), while pts treated with IMA had higher rates of comorbidities/concomitant drugs (p<0.001). Twenty-six pts had only baseline data and were not evaluable for early adverse events: among the remaining 398 pts, 73 (18.6%) needed permanent frontline TKI discontinuation in the first 12 months, due to hematologic toxicity (11 pts, 2.8%), extra-hematologic toxicity (19 pts, 4.8%), primary resistance (38 pts, 9.5%), secondary resistance (1 pts, 0.3%), evolution in blast phase (2 pts, 0.6%) and unrelated death (2 pts, 0.6%). On the whole, 51/185 pts treated with IMA (27.6%) discontinued frontline TKI treatment versus 22/213 (10.3%) treated with 2G-TKI (p<0.001). Cumulative incidence of discontinuation at 12 months was 25.8% (95%CI 19.5 - 32.1) in pts treated with IMA versus 9.5% (95%CI 5.6 - 13.4) in pts treated with 2G-TKI (p<0.001). The difference remained significant also considering different Sokal risk groups [17.8% versus 4.5% in low risk (p=0.004), 34.4% versus 13.1% in intermediate risk (p=0.002) and 55.6% versus 13.8% in high risk (p=0.003)] Conclusions: Frontline treatment of pts in this age group is still heterogenous in the current clinical practice: concomitant diseases, which are very rare in younger pts, start to be more common in this age group and represent an important criterion of TKI choice. Present data seem to encourage the use of frontline 2G-TKI in this subset, but data on molecular response and late toxicities are warranted to complete present analysis

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Blood
Published
2024-11-05
DOI
https://doi.org/10.1182/blood-2024-207175
Primary Topic
Chronic Myeloid Leukemia Treatments
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article
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article

Baseline Features, Treatment Choice and Early Frontline TKI Permanent Discontinuation in Patients with Newly Diagnosed Chronic Myeloid Leukemia Aged 50 - 60 Years: A “Campus CML” Study

Sara Galimberti, Monica Bocchia, Roberto Latagliata, Alessandra Iurlo et al.
Blood
Chronic Myeloid Leukemia Treatments
article

Baseline Features, Treatment Choice and Early Frontline TKI Permanent Discontinuation in Patients with Newly Diagnosed Chronic Myeloid Leukemia Aged 50 - 60 Years: A “Campus CML” Study

Sara Galimberti, Monica Bocchia, Roberto Latagliata, Alessandra Iurlo, Isabella Capodanno, Atelda Romano, Monica Crugnola, Michele Pizzuti, Alessandro Maggi, Marco Santoro, Debora Luzi, Giuseppe Saglio, Mario Tiribelli, Cristina Bucelli, Anna Rita Scortechini, Francesco Cavazzini, Jolanda Donatella Vincelli, Chiara Elena, Elena Crisà, Pamela Murgano, Giuseppina Loglisci, Immacolata Attolico, Federica Sorà, Ambra Di Veroli, Francesca Lunghi, Maria Cristina Miggiano, Giorgina Specchia, Elisabetta Abruzzese, Ida Carmosino, Massimiliano Bonifacio, Giovanni Caocci, Fabio Stagno, Gianni Binotto, Luigiana Luciano, Rikard Mullai, Paolo Sportoletti, Alessandra Malato, Sabrina Leonetti Crescenzi, Massimo Breccia, Carmen Fava, Sabina Russo, Davide Rapezzi, Anna Paola Leporace
article en

Abstract

Introduction: Median age at diagnosis in patients (pts) with Chronic Myeloid Leukemia (CML) is 58 - 60 years: while Second Generation Tyrosine-Kinase Inhibitors (2G-TKIs) are preferred in younger pts and imatinib (IMA) in elderly pts, there is no definite consensus on the best choice in middle-aged cases Aim: To analyze initial features, choice of frontline TKI and early adverse events leading to permanent TKI discontinuation in the first 12 months from TKI start in newly diagnosed subjects aged 50 - 60 in a large real-life cohort of CML pts Methods: Among 1967 CML pts newly diagnosed from 1/2012 to 12/2019 in 38 Italian Centers participating at the “Campus CML” project, 424 (21.5%) aged 50 - 60 years: their features at diagnosis and during the first year of TKI treatment were collected and analyzed in the present report Results: According to responsible physician choice, 191 pts (45.0%) received frontline IMA and 233 (55.0%) a 2G-TKI (dasatinib in 78, nilotinib in 135). Comparing the main clinical features at diagnosis according to frontline TKI, pts treated with 2G-TKI had higher WBC count (69.0 vs 48.8 x 109/l, p=0.002) and int/high-risk Sokal score (55.6 vs 42.2%, p=0.006), while pts treated with IMA had higher rates of comorbidities/concomitant drugs (p<0.001). Twenty-six pts had only baseline data and were not evaluable for early adverse events: among the remaining 398 pts, 73 (18.6%) needed permanent frontline TKI discontinuation in the first 12 months, due to hematologic toxicity (11 pts, 2.8%), extra-hematologic toxicity (19 pts, 4.8%), primary resistance (38 pts, 9.5%), secondary resistance (1 pts, 0.3%), evolution in blast phase (2 pts, 0.6%) and unrelated death (2 pts, 0.6%). On the whole, 51/185 pts treated with IMA (27.6%) discontinued frontline TKI treatment versus 22/213 (10.3%) treated with 2G-TKI (p<0.001). Cumulative incidence of discontinuation at 12 months was 25.8% (95%CI 19.5 - 32.1) in pts treated with IMA versus 9.5% (95%CI 5.6 - 13.4) in pts treated with 2G-TKI (p<0.001). The difference remained significant also considering different Sokal risk groups [17.8% versus 4.5% in low risk (p=0.004), 34.4% versus 13.1% in intermediate risk (p=0.002) and 55.6% versus 13.8% in high risk (p=0.003)] Conclusions: Frontline treatment of pts in this age group is still heterogenous in the current clinical practice: concomitant diseases, which are very rare in younger pts, start to be more common in this age group and represent an important criterion of TKI choice. Present data seem to encourage the use of frontline 2G-TKI in this subset, but data on molecular response and late toxicities are warranted to complete present analysis

BloodVol. 144(Supplement 1)
University of Siena (IT), University of Pisa (IT), University of Messina (IT), University of Verona (IT), Marche Polytechnic University (IT), University of Parma (IT), University of Udine (IT), University of Padua (IT), Vita-Salute San Raffaele University (IT), University of Cagliari (IT), University of Ferrara (IT), University of Perugia (IT), Azienda Ospedaliera San Giovanni Addolorata (IT), Policlinico Umberto I (IT), Agostino Gemelli University Polyclinic (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Ospedale Maggiore (IT), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), ASL Roma (IT), Azienda ospedaliera "Bianchi-Melacrino-Morelli" (IT), Ospedale Vincenzo Cervello (IT), Ospedale San Carlo (IT), Azienda Ospedaliera S.Giuseppe Moscati (IT), Federico II University Hospital (IT), Azienda Ospedaliera Sant'Andrea (IT), Arcispedale Sant'Anna (IT), Ospedale di Belcolle (IT), A. O. Ordine Mauriziano di Torino (IT), National Cancer Institute (MY), Azienda Ospedaliera Universitaria Senese (IT), St. Eugenio Hospital (IT), Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" di Palermo (IT), Policlinico San Matteo Fondazione (IT), Ospedale San Bortolo (IT), Ospedale Vito Fazzi (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), ASM Terni (Italy) (IT), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), University of Turin (IT), University of Bari Aldo Moro (IT), Sapienza University of Rome (IT)
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Chronic Myeloid Leukemia Treatments
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