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BSH 2022 | How the AML treatment landscape has evolved with the use of novel combination therapies

Pramila Krishnamurthy, King’s College Hospital NHS Foundation Trust, London, UK, shares some insights into how the treatment landscape of acute myeloid leukemia (AML) has evolved, and how novel therapies have made an impact. Dr Krishnamurthy first discusses AML treatment in the past, which mainly consisted of cytotoxic chemotherapy for those who were fit. Dr Krishnamurthy then explains how novel therapies are transforming AML treatment, including the use of midostaurin for FLT3-mutated AML, as well as IDH inhibitors. Dr Krishnamurthy then discusses how novel antibodies such as magrolimab, as seen in the ENHANCE study (NCT04313881), are improving therapeutic options. To conclude, Dr Krishnamurthy mentions the use of CPX-351 in patients with therapy-related myelodysplastic syndromes (MDS), and explains how AML treatment is becoming more personalized, providing more hope for patients. This interview took place at the 62nd Annual Scientific Meeting of the British Society for Haematology (BSH) 2022, in Manchester, UK.

Transcript (edited for clarity)

So when you consider that only a few years ago, our only real options for treating patients were standard cytotoxic chemotherapy agents, so we had daunorubicin and cytarabine for those patients who were fit. And over the last few years, we’ve really seen an explosion in the novel, more targeted agents for these patients. So for example, in the case of FLT3-mutated AML, we’ve got the data from RATIFY and the approval through NICE to allow us to use midostaurin, which clearly has impact on the responses to treatment in FLT3-mutated patients...

So when you consider that only a few years ago, our only real options for treating patients were standard cytotoxic chemotherapy agents, so we had daunorubicin and cytarabine for those patients who were fit. And over the last few years, we’ve really seen an explosion in the novel, more targeted agents for these patients. So for example, in the case of FLT3-mutated AML, we’ve got the data from RATIFY and the approval through NICE to allow us to use midostaurin, which clearly has impact on the responses to treatment in FLT3-mutated patients.

In terms of other targeted agents, we’re obviously seeing some role for the IDH inhibitors, although they’re not accessible to us in the UK at present, but things could change in the future. And I think also we’re seeing movement towards other sort of novel types of treatment strategy, meaning immunotherapy, which is starting to be a growing area for AML patients. And again, something that really didn’t exist before.

So we have novel antibody therapy such as magrolimab, which is coming to the UK in the ENHANCE studies, and it would be really exciting to see, to be able to treat patients with that agent and see how we get on. There have been other antibodies that we’ve been using, for example, a DART or a dual affinity redirected agent against CD123 and CD3, which had some excellent initial data in the early phase studies, particularly in patients with poor-risk AML. So I think things are changing. We’ve got a number of new drugs. We’ve got the first generation, second generation FLT3 inhibitors, other targeted agents, as I’ve mentioned.

I think we also have standard drugs that have been incorporated such as mylotarg, which has now become pretty much a regular treatment for us, for those patients who have CD33 positive AML. And so I think we are using that standard backbone of anthracycline-based chemotherapy, but we’re advancing that with the addition of more personalized treatment. And of course, for those patients who have AML with myelodysplasia-related changes or therapy-related MDS, we are able to use CPX-351. And as things are advancing, we’re seeing more and more combination treatments. So venetoclax, which is showing such great promise and activity. Predominantly it’s been used in those less fit patients and is now being incorporated into regimens for patients who are fit for chemotherapy.

So we will probably see that start to emerge in the earlier course of treatment for patients. And that could move us further and further away from the standard cytotoxic chemotherapy agents that have significant toxicities of their own. That perhaps means that we get better control of leukemia. For those patients who don’t go onto transplant, perhaps we’ll see greater depth of remission, longer duration of remission. Those patients who go to transplant, potentially a deeper remission pre-transplant, which will then have impact on their outcome following transplant.

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Disclosures

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