EURO-SKI indicates TKI discontinuation ‘feasible and safe’
medwireNews: EURO-SKI study findings add to the understanding on the best management of chronic myeloid leukemia (CML) patients who may be suitable for a trial of tyrosine kinase inhibitor (TKI) therapy discontinuation.
The results were presented by Francois-Xavier Mahon (University of Bordeaux, France) at the 2016 Annual Meeting & Exposition of the American Society of Hematology, held in San Diego, California, USA.
He included information on 758 trial participants who had used a TKI for at least 3 years (median 7.5 years) and maintained a deep molecular response (BCR–ABL1 <0.01% on the international scale; MR4) for at least 1 year (median 4.7 years) before attempting to discontinue treatment.
The 755 assessable patients who intended to stop treatment were followed-up for a median of 14.9 months, during which time 373 lost their major molecular response (MMR; BCR–ABL1 >0.1%). Patients without events were followed up for a median of 26 months.
The majority (78.3%) of molecular recurrences occurred within 6 months of discontinuation; the molecular recurrence-free survival (MRFS) rate was 61% at 6 months, 55% at 12 months, 52% at 18 months and 50% at 24 months. At 36 months, 47% of patients were still free from recurrence.
Of the 373 patients who restarted TKI therapy, 86.0% regained MMR and 80.1% MR4.
Dr Mahon explained that 72 patients had experienced a BCR–ABL1 greater than 1% and 11 had lost their cytogenetic response but that none of the patients progressed to accelerated phase CML or blast crisis. And none of the 10 deaths during the trial were attributed to CML.
The likelihood of MRFS at 6 months was significantly predicted by treatment duration of imatinib and the duration of MR4 before discontinuation, as well as the duration of interferon before TKI therapy.
By contrast, 6-month MRFS was independent of patient age, gender, the depth of their molecular response (MR4.5 vs MR4), or scores on the Sokal, EURO, EUTOS or ELTS measures.
Examining the impact of treatment duration cutoff on the likelihood of MMR loss after 6 months, the team identified 5.8 years as the point that showed the greatest significant difference, with a recurrence probability of 34% for patients who had taken the TKI for at least this time versus 57% for those with a shorter duration.
Furthermore, prognostic modelling using data from 405 patients given imatinib identified a cutoff of 3.1 years as the optimal duration of MR4 before discontinuation, giving a 38% probability of recurrence for patients who achieved at least this duration versus 56% for shorter duration.
Mahon added that the EURO-SKI trial was calculated to have spared patients a total of 8092 months of imatinib treatment, translating to an estimated saving of € 22 million (US$ 23 million).
“With inclusion and relapse criteria less strict than in many previous trials, and with decentralized but standardized [polymerase chain reaction]-monitoring, stopping of TKI therapy in a large cohort of CML patients appears feasible and safe,” the presenter summarized.
He concluded that the study supports the “opportunity to edit new European LeukemiaNet recommendations taking into account cessation of TKI” therapy.
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