EURO-SKI confirms TKI discontinuation ‘feasible’ for selected CML patients
medwireNews: EURO-SKI trial results support discontinuation of tyrosine kinase inhibitor (TKI) therapy in carefully chosen patients with chronic myeloid leukaemia (CML) in the chronic phase.
Molecular relapse-free survival at 6 months was reported for 62% of 750 patients who discontinued their TKI therapy after a median of 7.6 years of treatment. And 56%, 52% and 49% of patients remained free from molecular relapse at 12, 24 and 36 months, respectively.
“With inclusion and relapse criteria less strict than in many previous trials, and with decentralized but standardized PCR [polymerase chain reaction] monitoring, stopping of TKI therapy in a very large cohort of CML-patients appears feasible and safe”, presenting author Johan Richter (Skåne University Hospital, Lund, Sweden) told the 21st Congress of the European Hematology Association, held in Copenhagen, Demark.
In all, 868 patients were pre-registered for the study at 61 sites in 11 European countries and considered for TKI discontinuation after at least 3 years of first-line TKI therapy or second-line therapy due to initial TKI inhibitor toxicity.
In addition, participants were required to have typical BCR–ABL1 transcripts and demonstrated to have had a deep molecular response for at least a year, defined as PCR results showing BCR–ABL1 <0.01% (MR4) on the international scale on at least three occasions.
Relapse occurred in 347 patients, affecting 37%, 43%, 47% and 50% by 6, 12, 24 and 36 months. Eleven patients lost complete cytogenetic response and 72 patients had BCR–ABL1 >1%, and 14 patients reinitiated TKI therapy without relapse. There were no cases of progression to accelerated phase or blast crisis, and no CML-related deaths.
Patients began treatment after a median of 4.1 months and so far during the follow-up, 80% of relapsed patients have regained MR4, the presenter said.
Prognostic modelling of 448 imatinib-treated patients revealed that major molecular response (MMR) status 6 months after TKI discontinuation was independent of patient age, depth of MR response or patient Sokal, EUROS, EUTOS or ELTS scores.
However, MMR at 6 months was significantly predicted by TKI treatment duration (odds ratio [OR]=1.16 for each additional year of imatinib therapy) and MR4 duration (OR=1.16 for each additional year before discontinuation).
And 65.5% of patients who had received at least 5.8 years of imatinib achieved molecular relapse-free survival at 6 months compared with just 42.6% of those who had used the TKI for a shorter time.
Noting that the two variables are “highly correlated”, the researchers now aim to determine the optimal cutoff for MR4 duration, devise a predictive model for molecular relapse-free response and investigate the potential impact of interferon pretreatment on MMR duration after TKI discontinuation.
Finally, as reported in earlier studies of TKI discontinuation, newly emerging musculoskeletal symptoms were reported in around 30% of EURO-SKI patients, Richter said. Grade 1–2 events occurred in 29.7% and grade 3 events in 1.2%.
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