Blood cancers

CML patients can achieve treatment free remission after switching to nilotinib


Long term treatment free remission can be achieved in most chronic myeloid leukaemia patients who show a deep molecular response with second-line nilotinib therapy, researchers from South Australia have shown in a multinational trial.

The findings come from a trial led by researchers from South Australian Health and Medical Research Institute, who studied 163 patients with chronic phase chronic myeloid leukaemia (CML) who had achieved a sustained deep molecular response after switching from imatinib to nilotinib.

There were 126 (77%) patients who maintained a molecular response during a consolidation phase and were deemed eligible to stop nilotinib treatment. Of these, 58% maintained treatment free response at 48 weeks following withdrawal of the tyrosine kinase inhibitor (TKI) treatment and 53% maintained it at 96 weeks.

Of the 56 patients who restarted nilotinib therapy, all but one regained a major molecular response and 52 regained MR4.5

None of the patients had CML progression to accelerated phase or blast crisis.

The findings of the Novartis-funded Phase 2 trial, published in Annals of Internal Medicine, showed that CML patients who have achieved a deep molecular response on second-line TKI therapy could be considered potentially eligible for treatment free remission attempts.

“We found that over 50% of patients have maintained treatment-free remission after two years of observation, suggesting that this is a reasonable option for patients who have received second-line nilotinib,” said Professor Tim Hughes, Consultant Haematologist at the Royal Adelaide Hospital and SAHMRI’s Cancer Theme Leader.

“Other studies have suggested that patients who switched from imatinib to a more potent kinase inhibitor had a much lower probability of achieving treatment-free remission if the reason for switching was poor response, compared to patients who switched for poor tolerance. We didn’t observe this difference in this study.

“Importantly, we also documented that over 90% of patients who needed to restart their nilotinib therapy achieved a deep molecular response within 12 months of restarting.”

The researchers also concluded that for patients who do not achieve sustained DMR with imatinib, switching to nilotinib may enable more patients to become eligible for TFR.

“Through using these more potent tyrosine kinase inhibitors, it would appear that we can recruit more patients to treatment free remission, which is great news,” Professor Hughes said.

However careful patient selection was important to ensure the safety of treatment discontinuation, they added

In CML, deep molecular response is defined as a reduction in the amount of circulating leukaemic cells from 100% down to less than 0.01% – a four log reduction in the overall number of leukaemic cells – and is the prerequisite for an attempt at treatment-free remission.

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