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The e13a2 BCR‐ABL transcript negatively affects sustained deep molecular response and the achievement of treatment‐free remission in patients with chronic myeloid leukemia who receive tyrosine kinase inhibitors
Author(s) -
D'Adda Mariella,
Farina Mirko,
Schieppati Francesca,
Borlenghi Erika,
Bottelli Chiara,
Cerqui Elisa,
Ferrari Samantha,
Gramegna Doriana,
Pagani Chiara,
Passi Angela,
Maifredi Adriana,
Tucci Alessandra,
Capucci Maria A.,
Ruggeri Giuseppina,
Rossi Giuseppe
Publication year - 2019
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.31977
Subject(s) - medicine , discontinuation , myeloid leukemia , tyrosine kinase inhibitor , tyrosine kinase , breakpoint cluster region , oncology , immunology , cancer , receptor
Background Stopping tyrosine kinase inhibitor (TKI) treatment has become a realistic and safe objective for patients who have chronic myeloid leukemia (CML). Both a sustained deep molecular response (sDMR) and the lack of a molecular recurrence after TKI discontinuation are required to reach a durable treatment‐free remission (TFR). Methods The potential predictive role of BCR‐ABL transcripts in attaining an sDMR and a TFR was analyzed in a strictly consecutive, unselected series of 194 patients who were diagnosed and treated with TKIs at the authors’ center. Results Of 173 fully evaluable patients, 67 (38.7%) had the e13a2 transcript, and 106 (61.3%) had the e14a2 transcript. Complete cytogenetic and major molecular remissions were not affected, whereas the achievement of both a DMR ( P = .008) and an sDMR ( P = .004) was favored significantly in patients who had the e14a2 transcript. After a median of 68 months, the sDMR rate was 39.6% in those with the e14a2 transcript and 19.4% in those with the e13a2 transcript. In addition to transcript type, both the early achievement of a molecular response and starting treatment with a second‐generation TKI positively affected the attainment of an sDMR in multivariate analysis. The use of a second‐generation TKI as frontline treatment increased the sDMR rate in both transcript types. However, in patients who had the e13a2 transcript, the probability of attaining an sDMR was 37% after 60 months and did not increase further despite continuing therapy. Among 51 of 60 patients who attained an sDMR after discontinuing TKIs, 24 experienced a molecular relapse, but all regained molecular remission after resuming TKI treatment. Again, transcript type influenced TFR maintenance ( P = .005), because only 2 patients (3%) with the e13a2 transcript enjoyed a durable TFR compared with 25 (23.5%) of those with the e14a2 transcript. Conclusions The e13a2 transcript hinders the achievement of deep responses and the possibility of stopping TKI treatment in patients with CML.