General and British Society of Haematology (BSH) updates

In our Spring edition of Leukaemia Matters, we reported that venetoclax with azacitidine for newly diagnosed acute myeloid leukaemia (AML) patients who are unsuitable for chemotherapy had been approved by the National Institute for Health and Care Excellence (NICE) for use on the NHS in England. We are now pleased to announce that the same treatment has been approved for the same group of patients in Scotland via the Scottish Medicines Consortium (SMC).

We have also contributed to the appraisal of oral azacitidine as a maintenance treatment for AML in England, to be used after chemotherapy to prevent relapse. We will continue to be involved in this until NICE reaches a decision about whether to approve it on the NHS.

In other news, according to the British Society of Haematology (BSH), researchers have developed a new chimeric antigen receptor CAR T-cell therapy which could one day bring the life-saving benefits of the treatment to patients with AML.

Updates from BSH

There were a number of updates from various clinical trials in adult acute lymphoblastic leukaemia (ALL) which were shared at BSH this year – these updates are for adult ALL clinical trials. Here were some of the key findings from these discussions.

UKALL14 – What is it?

UKALL14 is a phase three randomised control trial (RCT) for newly diagnosed (de novo) ALL patients aged between 25-65. The aim of the trial was to find out whether adding an additional treatment into the induction phase would be beneficial to patients.

The trial was split into different parts to accommodate the different subtypes of ALL.

Professor Adele Fielding, the Chief Investigator of UKALL14, kicked off the session at BSH by discussing some of the outcomes gathered during this trial.

Reduced rate of relapse in patients with B-cell ALL who received rituximab before transplant

As part of the trial B cell-ALL, patients were randomised to receive standard of care therapy during the first phase of induction, or standard therapy plus rituximab. Rituximab is a type of immunotherapy that targets a molecule called CD20, which is commonly found on leukemic B cells. Rituximab has previously shown great success in treating chronic lymphocytic leukaemia (CLL) patients and other B-cell malignancies. Professor Fielding stated that one of the findings during the UKALL14 trial was that CD20 was an attractive target for treatments.

The study found that there was a substantial benefit to patients who received rituximab before their transplant. They survived for long periods without relapse or other significant problems and it also resulted in a reduction in relapse rates amongst these patients.

We are pleased to have written a patient group submission for The National Institute for Health and Care Excellence (NICE) appraisal of asciminib for treating chronic myeloid leukaemia (CML) after two or more tyrosine kinase inhibitors (TKIs) in England. We will continue to be involved and represent the experience of CML patients for this appraisal this year until it concludes.

Updates from BSH

At conferences, as well as oral presentations, there is also an opportunity to share research in a written format, which are then displayed as posters. This is often a good opportunity for smaller studies to be shared.

In CML, there was a study presented by researchers from Queen’s Hospital Barking, a district general hospital. These types of hospitals are often less likely to have staff specialised in rare conditions like CML, so it is important to see how these hospitals manage patients and ensure they are able to support their patients as larger hospitals would. This study discussed the number of patients with CML taking dasatinib who have experienced pleural effusion at their hospital. Pleural effusion is a side effect that involves fluid on the lungs. This study observed that 35% of their patients were affected by pleural effusion, but not the same people who have been shown to be at higher risk of pleural effusion in other studies (e.g. smoking status seemed less important at this particular hospital). Studies such as this help hospitals to reflect on their practices; the study reports most cases were mild to moderate and managed effectively by the hospital. 

As you may already be aware, we have been involved in the National Institute for Health and Care Excellence (NICE) appraisal of duvelisib for treating relapsed or refractory chronic lymphocytic leukaemia (CLL) after at least two prior treatments since it started. However, unfortunately, in March we were disappointed to learn that this appraisal had been cancelled, and NICE will not be launching the treatment in England.

We are, however, pleased to announce that other treatments have been approved for CLL patients since the Spring. Venetoclax with obinutuzumab for the treatment of adult patients with previously untreated CLL has now also been approved by the Scottish Medicines Consortium (SMC) for use in Scotland.

In the previous Spring Leukaemia Matters edition, we mentioned that an appraisal we submitted evidence for, venetoclax monotherapy for CLL, was in the Cancer Drugs Fund, i.e. approved temporarily in order to gather more real-world evidence to make a decision about whether to approve it permanently. We are pleased to update that following a review of the data, this treatment has now been approved permanently by NICE for use in Egland.

BSH updates

The CLL session at BSH covered a wide range of topics, showing how CLL is still a disease with much to be understood, despite being the most common form of leukaemia.

The first presentation was from Professor Anna Schuh from Oxford, on the topic of the genomics of CLL. Genomics is the study of the DNA within CLL cells. This is important as the reason why cells become cancerous is determined by expression of genes in the cells – the cancer cells survive either by making too much of something that they shouldn’t (over-express a gene) or making too little of something (under-expressing genes). We have known for a while that certain genetic changes make CLL cells harder to treat and more likely to survive. Examples include TP53/17p mutations; Professor Schuh updated that testing new guidelines from the World Health Organisation now say tests for these genetic mutations that are known to impact on CLL treatment outcomes are essential before treatment of CLL (this has been the case in other guidelines for a while and testing in the UK is common).

She also provided an update about mutations as part of the DNA of CLL cells that are not genes. These are called non-coding regions and although they don’t direct cells to make proteins like genes do, they are still important to the cell. One role they play is to fold up the DNA in a way that stops genes from being read by the cell, thereby affecting the production of proteins from genes. Professor Schuh presented work that suggests mutations in some of these non-coding regions may also be important to the survival of CLL cells, as well as mutations to the actual genes. It is not yet clear how this information can be used to treat CLL, as the work is at an early stage. The work does highlight how complicated cells are and how much more there is to be understood about the basic biology of the disease. 

Other talks at this session included:

• Professor Barbara Eichorst of Germany, who discussed treatment options in CLL. We now have two broad camps of CLL treatments; continuous treatments and treatments taken for a certain time period. It is an ongoing debate as to which type of treatment is most effective in different groups of CLL patients – Professor Eichorst felt this was an area that needed further exploration, as well as further clarification on the best order for treatments to be had. Patient preference for certain types of treatment was not discussed, which should be a part of any decision choosing between two treatments.
• Professor Renata Walewska finished the session by outlining the newest clinical guidelines for treating CLL. An update to the treatment guidelines was needed thanks to the approval of several new treatments for use on the NHS (e.g. venetoclax with obinutuzumab in 2021) in a short space of time, many of which we shared in recent editions of these magazines. These new treatments have led to chemotherapy being recommended for fewer patients, in favour of some newer treatments. There have also been guidelines published for doctors on how to better involve patients in decision around their care. All this new information has been incorporated into new advice for doctors treating CLL; the guidelines can be read here.

We have been involved in the appraisal of a medicine called ropeginterferon alfa-2b (Besremi), for use in adults with polycythaemia vera (PV) without symptomatic splenomegaly by the Scottish Medicines Consortium (SMC) in Scotland, and represented patients at the committee meeting in April. The decision about the approval of this treatment will be made public on the 9th May. 

SMC is striving to minimise any delays in patient access to treatments and reduce demand on their Committee members (e.g clinicians) as pressures on NHS clinical staff due to the COVID-19 pandemic continue. As a result, SMC has decided that new medicines, where alternatives within the same therapeutic class have previously been accepted for use (or restricted use) by SMC, may be eligible for the abbreviated submission process. This means these medicines are fast-tracked to ‘accepted advice’ after review by the SMC Executive and do not require a Patient Group Submission, or to be considered by the full SMC Committee.

The medicine fedratinib (Inrebic) – for treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis who are JAK inhibitor naïve or who have been treated with ruxolitinib – has been fast-tracked in this way and is now available for use on the NHS in Scotland.

BHS updates

One presentation at BSH that was of interest was a presentation on the new learnings about blast phase MPNs. Blast phase means that a person has either been diagnosed when the illness is already aggressive (most patients are diagnosed at a chronic, slowly developing stage) or a person with a chronic MPN has developed a more aggressive version of their illness. The aggressive nature of a blast phase MPN makes it harder to treat, so Professor Adam Mead presented work where researchers are working to better understand blast phase MPNs and better treat them as a result. 

It was shown that 65% of people who develop blast phase MPNs share a particular set of genetic mutations in their DNA. Professor Mead aims to understand these in order to see if any of the mutations can be targeted for a treatment. He particularly focused on a mutation in the TP53 genes. It was found that some people gain TP53 and unfortunately develop a leukaemia, but many do not. Therefore, this means it’s not enough to gain a mutation in order to progress to a blast phase MPN or a leukaemia; something else is also at play. We need to understand what these other factors are, to help us predict people who might develop blast phase illness or leukaemia and hopefully intervene earlier.

There was also a presentation by Dr Quek of London on updates in the management and treatment of MDS. Firstly she shared some updates to the clinical guidelines on how to manage and treat MDS. Updates of interest included:

• Better clinical definitions of precursor conditions to MDS. Some people are identified as having problems with their blood or bone marrow but do not meet the definition of MDS; it is important to define and understand these precursor conditions to be able to give these patients an accurate diagnosis. 
• A recommendation to ensure doctors are more closely monitoring those who are about to start treatment but have low-risk MDS, as it can be harder to treat high-risk MDS and so it is important to ensure this is prevented from happening.
• An update on who is most likely to benefit from treatment with erythropoietin; it’s important that treatment is only given when it is more likely to benefit the person than do harm since all treatments have side effects. 

Dr Quek also highlighted the number of clinical trials currently open to MDS patients. There is a significant number of monoclonal antibody treatments being trialed for high-risk MDS, plus ongoing studies of treatments also tested for acute myeloid leukaemia in the past. However, fewer options for trials remain for people with low-risk MDS, where more treatment options are needed. 

We recently submitted a response to the Government’s call for evidence for the 10-year cancer plan, highlighting issues facing leukaemia patients from early diagnosis to innovative treatments. Read our full blog here.

We also submitted a consultation response to a review of NHS clinical standards. Cancer currently has a set of nine performance standards, with different targets covering different routes into the system. The proposed changes to the clinical standards will simplify this and include, for example, a target to have cancer ruled out or diagnosed within 28 days following urgent referral. This would potentially replace the existing two-week wait pathway between referral and an appointment with a specialist. The aim is to improve faster diagnosis. In our response, we shared our thoughts on how this would impact leukaemia patients and included any areas of concern.

We have also recently met with several MPs as part of the Blood Cancer Alliance’s work on our ForgottenFifth campaign. This is to raise awareness of the unique issues blood cancer patients face and push for blood cancers to receive the same attention in NHS and governmental strategic documents as those with the biggest four cancers.

Lastly, we contributed to discussions with NHS digital and NHS England on the digital cohort of eligible groups for the COVID-19 antiviral treatments alongside CLL Support, MDS UK and Blood Cancer UK. As a result, we continue to highlight and resolve any issues together and to ensure that those who were mistakenly left out of the original digital cohorting are now included (e.g. chronic myelomonocytic leukaemia (CMML) patients).