Blood cancers

TKI discontinuation in routine practice matches success in clinical trial settings for CML: Study

Discontinuation of tyrosine kinase inhibitor (TKI) therapy for chronic myeloid (CML) leukaemia patients is largely as successful in real-world clinical practice as it is in clinical trial settings, according to a new study conducted in Sweden.

“Initially considered to be a lifelong treatment, several TKI discontinuation trials have shown that approximately 40–50% of patients with sustained DMR [deep molecular response] can successfully discontinue TKI and attain a treatment‐free remission (TFR),” wrote study authors led by Dr Hjalmar Flygt, of University Hospital in Uppsala.

Data on TKI discontinuation outside of clinical trial settings, however, remains very limited. The new study examined outcomes from 584 patients from the Swedish CML registry diagnosed with chronic-phase CML between 2007 and 2012, of whom 548 had evaluable information on discontinuation of therapy. The results were published in the British Journal of Haematology.

A total of 128 patients (23%) discontinued TKI therapy for at least one month due to achieving a DMR; 38 of those patients (29.7%) did so within the context of a clinical study, while 90 (70.3%) discontinued therapy in routine care.

Among all patients with a DMR who discontinued therapy, the probability of TKI re-initiation at 12 months was 47.8%. For patients inside clinical trials, the probability of restarting TKI therapy at 24 months was 73.7%, compared with 41.4% for those outside trials. At 48 months, the rate was 76.6% for those in trials and 52.5% for those in routine care.

A total of 56 patients (62.2%) outside of clinical trials were treatment-free after a median follow-up of 1.6 years. Those in the trials did have a shorter time from diagnosis to discontinuation than those outside the trials (4.2 years vs 6.2 years; p < .001).

“Our results from a population‐based study show that TKI discontinuation in CML in clinical practice is common and feasible and as successful as when performed within a clinical trial,” the authors concluded.

Prof Richard Clark, of the University of Liverpool, who was not involved in this study but has led others involving TKI discontinuation (including the DESTINY trial), told the limbic that the Swedish results are “interesting.” He pointed out that such studies are more likely to be done in Sweden given its requirement to centrally report all cancer cases. “Something similar would not be possible in the UK as inevitably it would only capture a minority of cases – and those mostly at well motivated/staffed centres where results are likely to be better,” he said.

Prof Clark participated in a UK Interim Expert Opinion issued in 2017 on TKI discontinuation, which recommended its use if certain stringent criteria are met. He said the impact of the Swedish results will likely not be dramatic here. “The DESTINY strategy has been taken up by most British haematologists, namely having a period of de-escalation before stopping.” Such a strategy, he added, does appear to select for patients who will relapse if treatment is stopped completely.

“However, it remains important to see the encouraging DESTINY data confirmed in other studies,” Prof Clark said.

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