TY - JOUR
T1 - Risk of progression in chronic phase-chronic myeloid leukemia patients eligible for tyrosine kinase inhibitor discontinuation
T2 - Final analysis of the TFR-PRO study
AU - Zambrotta, Giovanni Paolo Maria
AU - Nicolini, Franck E.
AU - Assouline, Sarit
AU - Busque, Lambert
AU - Pungolino, Ester
AU - Abruzzese, Elisabetta
AU - Miggiano, Maria Cristina
AU - Elena, Chiara
AU - Alvarez-Larran, Alberto
AU - Triguero, Ana
AU - Iurlo, Alessandra
AU - Bucelli, Cristina
AU - Cerrano, Marco
AU - Capodanno, Isabella
AU - Lunghi, Francesca
AU - le Coutre, Philipp
AU - Galimberti, Sara
AU - Caocci, Giovanni
AU - Maffioli, Margherita
AU - Stagno, Fabio
AU - Saussele, Susanne
AU - Piazza, Rocco
AU - Druker, Brian J.
AU - Fava, Carmen
AU - Guglielmana, Veronica
AU - Colombo, Federica
AU - Antolini, Laura
AU - Gambacorti-Passerini, Carlo
N1 - Publisher Copyright:
© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
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U2 - 10.1002/ajh.27073
DO - 10.1002/ajh.27073
M3 - Article
C2 - 37647134
AN - SCOPUS:85169689931
SN - 0361-8609
VL - 98
SP - 1762
EP - 1771
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 11
ER -