Blood cancers

Treatment free remission is a realistic goal in CML: new guidelines


New recommendations for management of CML have emphasised the goal of treatment free remission (TFR).

In a substantial update from their 2013 recommendations, a European LeukemiaNet panel of experts including Australian Professor Timothy Hughes said a significant proportion of patients will achieve a deep molecular response (DMR) with the familiar TKIs.

“An attempt at treatment discontinuation can be considered, if sustained DMR of sufficiently long duration has been achieved,” they said.

The recommendations reiterated the importance of generic imatinib as first line therapy for CML.

They said the 5-year probability of achieving a DMR (MR4 or deeper) following imatinib treatment ranges between 35 and 68%.

The recommendations also highlighted the new EUTOS Long-Term Survival (ELTS) score was now the appropriate tool for determining a patient’s risk status at diagnosis.

Professor Hughes, from SA Pathology and SAHMRI, told the limbic that while Sokal scores still had some value, the ELTS score looked to be better score in the current environment of kinase inhibitor therapy.

“We’ve used the Sokal score for many years ….but it was really designed for people treated in those days with quite an effective therapy and yet most of them were dying in 2-3 years.”

“And the advantage of ELTS is it uses exactly the same variables – the age, the platelet count, the blast counts and the spleen size – so you can feed in exactly the same variables into a different formulae and get a slightly different number that is more helpful for us than the Sokal score.”

He said there was much enthusiasm about five years ago for getting patients onto the second generation drugs because the evidence was pretty strong that you could achieve deeper responses and achieve them earlier with the more potent drugs like dasatinib and nilotinib.

“And then we started to see the toxicity of the second generation drugs mainly in terms of the vascular toxicity – heart attacks, strokes, claudication in the legs…,” he said.

“That has probably caused clinicians to pull back a bit on their usage and probably confine them more to the younger patients where you are not so concerned about vascular toxicity, and use imatinib as a safer drug for patients over 60.”

He said that TFR was probably only being achieved in about 20-25% of patients currently but “if the drugs are used appropriately and used swiftly where it is indicated you could probably substantially increase that rate of TFR to closer to 50%”.

“When we first started using these drugs 20 years ago, we thought they were going to prolong survival and then we thought maybe they could do more than that and keep people alive but on drug – chronic therapy – and now we use the drugs to get the deepest response, sustain it and then get them off drugs successfully. Most patients would say that is what they want.”

In Australia, the PBAC’s Drug Utilisation Sub-Committee (DUSC) has recently reported that the number of CML patients treated with TKis was growing in a linear manner.

“The majority of this use was for patients in the chronic phase of disease being treated with their first line medicine. The second highest group is patients in the chronic phase of disease being treated with their second line medicine.”

Imatinib was the most commonly used TKi for CML, however the use of nilotinib and dasatinib increased over the study period 2001-2019 which included a number of changes to PBS restrictions.

The use of ponatinib was small in the context of the CML market; 50 patients were treated with ponatinib in 2018.

DUSC commented that the top ten medicine sequences showed that the majority of patients were treated with only one agent, which suggests patients tend to stay on the original TKI therapy they are initiated on rather than switching to new therapies.

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