Research updates from the American Society of Hematology (ASH) conference

Quizartinib

A potential new treatment for AML, quizartinib, is currently being assessed by The National Institute for Health and Care Excellence (NICE). NICE is looking at the evidence to decide whether quizartinib should be available on the NHS in England. (Wales and Northern Ireland usually follow NICE guidance. Scotland has a separate system for assessing medicines.)

What is already known about quizartinib?

Quizartinib is a targeted treatment that you take as an oral tablet once a day. It blocks a protein called FLT3, which is involved in cell growth and division. Quizartinib specifically blocks a version of the FLT3 protein made by a gene that has a change called a FLT3 ITD mutation. This mutation can make AML difficult to treat. In a trial called QuANTUM-First, 539 adults with newly-diagnosed AML and a FLT3 ITD mutation were randomly allocated to be treated with either:

• Standard chemotherapy plus quizartinib for induction and consolidation, followed by up to three years of quizartinib alone for maintenance.
• Standard chemotherapy plus dummy treatment (placebo) for induction and consolidation, followed by up to three years of placebo alone for maintenance.

This was published late last year. The study found that adding quizartinib to standard chemotherapy, followed by quizartinib alone for up to three years, improved overall survival in patients with newlydiagnosed AML and a FLT3 ITD mutation.

Average overall survival was 31·9 months for patients who had quizartinib compared with 15·1 months for patients who had placebo. Also, average length of complete remission was longer in patients who had quizartinib than those who had placebo (38·6 months compared to 12·4 months).

The rate of side effects was similar in both treatment groups, but patients taking quizartinib had a higher rate of serious side effects. These were managed through monitoring and dose reductions.

NICE takes into account both the clinical effectiveness and the cost of the treatment when it decides whether or not to approve the treatment. We will report the results of the process which are expected in October.

Potential new option for patients who have tried several current treatments

Tyrosine kinase inhibitors (TKIs) are generally very effective in treating CML. However, some people have CML that does not respond, or stops responding, to currently available TKIs. Others have side effects that mean they have to stop treatment.

A recent study, presented at the ASH conference at the end of 2023, has looked at a treatment called olverembatinib for treating chronic phase CML in people who have already had several TKIs. Olverembatinib is a new third-generation TKI that you take by mouth every other day.

In this study in China, 144 adults with chronic phase CML who had previously been treated with three or more TKIs were randomly allocated to either:

• Olverembatinib
• Best available therapy (BAT) – either a different TKI (imatinib, dasatinib or nilotinib), interferon, hydroxyurea or homoharringtonine

The trial found that olverembatinib was more effective than BAT.

More patients in the olveramatinib group than the BAT group achieved a major molecular response (27.3% compared to 8.1%).

This early Phase 2 study suggests that olverembatinib could be a promising treatment option for patients who have failed multiple TKIs. It will need further testing in larger clinical trials.

Kinder cancer treatments

A treatment for ALL hit the headlines in January, thanks to the option for patients to have it with them wherever they go. Here we answer some questions you might have about this treatment:

What is it?

Blinatumomab is a treatment that is known as a bi-specific antibody (BiTE). It works by attaching the leukaemia cells to a toxin that kills them, using an antibody as a bridge. It attaches to a protein specific to the ALL cells, so it’s less likely to cause side effects by attacking the non-cancer cells.

Isn’t it already available?

Yes. Adults with certain types of ALL can already be prescribed blinatumomab. The news story was highlighting a need for children to also get access.

What’s the benefit of this treatment compared to the usual treatment?

The haematologists in the piece believed that blinatumomab has fewer side effects on average. The piece also showed that patients can have it from home. The patient had it in his own bed, which he and his parents talk about being really important for his quality of life. However, it’s known that chemotherapy can put people in remission long term, whereas blinatumomab is too new to know that for sure. Also, blinatumomab does have side effects, so it may not be for everyone.

It’s important to discuss all options with your doctor. Leukaemia Care supports the call for blinatumomab to be considered, through the usual processes, as a routine option for children.

How to choose between transplantation and CAR-T?

Arguably the biggest change in treating ALL lately was the approval of CAR-T treatment on the NHS. However, for many decades, stem cell transplantation (SCT) has also been available. There are pros and cons to each treatment, and different information available. This leaves doctors and patients with a debate; which is best for who? At the recent meeting of the ASH conference, various doctors across America tried to answer this question. Dr Shah from the US National Institute of Health said that individual patient factors, like previous complications and donor availability, are more important in the decision than what is best for the hospital.

Dr Bertaina of Stanford University argued that working out the best order of treatment for maximum impact is more important. She said that more research into the biology of leukaemia cells might provide “markers” of certain groups of patients who would benefit from one treatment over another.

Finally, Dr Gossek of St Jude’s hospital in Tennessee pointed out that there remain some patients who do not benefit from either treatment and we still need more options after CAR-T. Overall, the session offered hope that we may find answers in the future, even if choices are not clear cut at present.

An update to the FLAIR trial

Research presented at the ASH conference in December last year mainly focused on learning more about the treatments we already have access to in the UK for the treatment of CLL. Many CLL patients diagnosed around 5 to 10 years ago will be familiar with the FLAIR trial. This was a trial that originally aimed to explore whether ibrutinib with rituximab was a more effective combination of treatment than FCR (chemotherapy made up of fludarabine, cyclosphosphamide and rituximab). It has, in more recent times, looked at other combinations of ibrutinib compared to FCR.

At the most recent annual meeting of ASH, Professor Hillmen from the UK presented the latest trial data comparing ibrutinib with venetoclax (I+V) with FCR. Both are treatments currently available, but it is useful to clinicians to continue to explore which treatments are best. There are several options available to most CLL patients now, so the order of treatments becomes important. Professor Hillmen and the team concluded that I+V improves progression free survival compared to FCR. At three years, 97% of I+V patients were still progression free (i.e. their disease did not get worse in that time), compared with 77% of patients who had FCR. Importantly, the research team also showed that you can measure the level of CLL cells left in the blood (known as minimal residual disease, MRD) of patients on I+V to help guide treatment duration.