This year, due to COVID-19, the 25th European Haematology Association (EHA) annual congress ran virtual sessions over 10 days starting from 11th June. The reason why we attend these conferences is to inform you about any interesting new developments in patient care, research and emerging treatments in the different leukaemia types. Different sessions ran each day according to a particular theme.
Treatment landscape in CLL
In the chronic lymphocytic leukaemia (CLL) field, there has been many developments of targeted treatments over the past few years. Researchers are looking to find the best possible combinations of these novel treatments, in both the front-line and relapsed/refractory settings. The EHA sessions this year reported on data from follow-up studies of treatment approaches using multiple drugs, often called combination treatments, that are currently in clinical trials.
Current targeted treatments – what do they do?
There are many different types of targeted therapies currently available or in development for CLL patients. This includes monoclonal antibodies, one example of which is obinutuzumab. It recognises and binds to a protein called CD20 on the surface of leukaemia cells. In doing so, it marks the cell for destruction by the immune system. Other types of targeted therapies are called inhibitors. These include venetoclax, a BCL-2 inhibitor. Leukaemia cells are dependent on the BCL-2 protein for their survival but venetoclax is able to bind to the BCL-2 protein and block this function, causing cell death of CLL cells.
Another exciting improvement within the treatment landscape has been the development of BTK inhibitors; ibrutinib is already in use in the UK and the acalabrutinib and zanubrutinib are in use elsewhere and in development here. The BTK protein is found on leukaemia cells, and it helps the cells survive and multiply. These BTK inhibitors are able to block this activity and stop leukaemia cells from surviving and multiplying.
Highlights - First-line untreated CLL
In the EHA sessions, updates from the phase 3 CLL14 trials were provided. This trial looked at a combination of venetoclax and obinutuzumab, which is continuing to show a significant improvement; 81.9% of patients who had the venetoclax combination survived for three years without their disease worsening (known as progression-free survival), compared to just 49.5% of patients taking chlorambucil and obinutuzumab, which was the standard of care when the trial began. This is good news as the treatment is now being appraised by NICE to see whether it should be approved for use on the NHS.
Encouraging data from a phase 2 trial using triple combinations was also presented. In this trial, the patients received a combination of obinutuzumab, venetoclax and ibrutinib for six months, then a combination of venetoclax and ibrutinib for another six months. Finally, if patients at this point did not achieve undetectable minimal residual disease (MRD) and complete remission, they were able to continue ibrutinib treatment. MRD is the presence of a small number of leukaemia cells that may remain and cause the patient to relapse in the future; you can read more about MRD here. In 58.55% of the patients, a complete remission was achieved and undetectable MRD was observed in 80.5% of patients. You can read more here.
Updates from the phase 2 CAPTIVATE study were also presented at EHA. This trial was a study of the combination of ibrutinib and venetoclax. The study reported promising results, with a high rate of undetectable MRD and tolerable side effects profile. This combination is as yet unavailable in the UK outside of clinical trials.
Highlights – relapsed/refractory CLL
EHA sessions also presented data from combination trials on relapsed/refractory patients. This included the CLARITY trial, which assessed the combination of ibrutinib and venetoclax. The study reported the treatment was well tolerated and showing promising early results, although further data is needed.
The ASCEND trial follow-up results of acalabrutinib were also reported at EHA, which confirmed that acalabrutinib is showing more potential than the standard treatment options available to relapsed/refractory patients, in terms of efficacy and safety profile. Use of acalabrutinib in this population is currently being assessed by NICE for use on the NHS.
The current trials are providing researchers with a better understanding of these treatment combinations, their side effects profile and how best to manage them, and what patients are more or less likely to respond to a particular treatment based on their disease genetics. The many ongoing clinical trials assessing the different combination approaches will allow the development of the best treatment options for both treated and untreated CLL patients.
Current challenges in treating CML
The EHA sessions on chronic myeloid leukaemia (CML) this year looked at understanding and tackling the issue of resistance to current treatments; these include the tyrosine kinase inhibitors. Tyrosine kinase is a type of protein that is involved in promoting growth and survival of cells; current CML treatments block the activity of a specific kinase present in CML cells and as a result prevent growth and survival of the leukaemia cells.
- Resistance to current TKI treatments
During the EHA sessions, haematologists discussed why patients may have resistance to TKI treatments at different stages and how this can be managed. The speakers also looked at multiple ways to improve TKI response. One suggestion was to adjust TKI doses, to improve efficacy and reduce side effects. A few studies were mentioned that are looking at identifying patients with certain mutations at diagnosis that may mean they are more likely to develop resistance to treatment. This will help provide suitable treatments early on to prevent resistance. They also looked at other exciting novel treatments that may be effective in patients that are resistant to the current TKI inhibitors.
- Current clinical trial on patients resistant to previous TKI treatments
Data from a phase 1 study of Asciminib were presented at EHA. Asciminib is also a TKI-inhibitor but works in a slightly different way to existing treatments. This unique function is expected to result in improved efficacy and safety. The study concluded: “Asciminib was well tolerated and showed promising clinical activity”. This was trialled in heavily pre-treated patients with resistance to at least two prior TKI therapies. The study also assessed combination with other TKI treatments, including imatinib, nilotinib and dasatinib, which is ongoing and data has not yet been published. During the EHA sessions, there were suggestions of how combination therapies could prove to be more effective than either therapy alone and may help tackle the resistance issue.
These EHA sessions provided an insight into the current challenges of CML treatments. The researchers are looking at ways to better understand and manage these challenges, so that CML patients are provided with more effective and well-tolerated treatment options in the future.