Risk of progression in chronic phase-chronic myeloid leukemia patients eligible for tyrosine kinase inhibitor discontinuation: Final analysis of the TFR-PRO study

Zambrotta, Giovanni Paolo Maria;Nicolini, Franck E;Assouline, Sarit;Busque, Lambert;Pungolino, Ester;Abruzzese, Elisabetta;Miggiano, Maria Cristina;Elena, Chiara;Alvarez-Larran, Alberto;Triguero, Ana;Iurlo, Alessandra;Bucelli, Cristina;Cerrano, Marco;Capodanno, Isabella;Lunghi, Francesca;le Coutre, Philipp;Galimberti, Sara;Caocci, Giovanni;Maffioli, Margherita;Stagno, Fabio;Saussele, Susanne;Piazza, Rocco;Druker, Brian J;Fava, Carmen;Guglielmana, Veronica;Colombo, Federica;Antolini, Laura;Gambacorti-Passerini, Carlo

2023-01-01

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Abstract

Disease progression to accelerated/blast phase (AP/BP) in patients with chronic phase chronic myeloid leukemia (CP-CML) after treatment discontinuation (TD) has never been systematically reported in clinical trials. However, recent reports of several such cases has raised concern. To estimate the risk of AP/BP among TD-eligible patients, we conducted TFR-PRO, a cohort retro-prospective study: 870 CP-CML patients eligible for TD formed a discontinuation cohort (505 patients) and a reference one (365 patients). The primary objective was the time adjusted rate (TAR) of progression in relation to TD. Secondary endpoints included the TAR of molecular relapse, that is, loss of major molecular response (MMR). With a median follow up of 5.5 years and 5188.2 person-years available, no events occurred in the TD cohort. One event of progression was registered 55 months after the end of TD, when the patient was contributing to the reference cohort. The TAR of progression was 0.019/100 person-years (95% CI [0.003-0.138]) in the overall group; 0.0 (95% CI [0-0.163]) in the discontinuation cohort; and 0.030 (95% CI [0.004-0.215]) in the reference cohort. These differences are not statistically significant. Molecular relapses occurred in 172/505 (34.1%) patients after TD, and in 64/365 (17.5%) patients in the reference cohort, p < .0001. Similar rates were observed in TD patients in first, second or third line of treatment. CML progression in patients eligible for TD is rare and not related to TD. Fears about the risk of disease progression among patients attempting TD should be dissipated.