Liz Burtally
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More blood cancer updates from EHA – the biggest haematology congress in Europe

Liz Burtally
Posted by
17 Jun 2018

Find out more about new research and treatments in AML, CLL, CML and graft versus host disease (GvHD).

I’m leaving Sweden today, and I will be sad to go. But before I do, I thought I would tell you about three talks that were included in the ‘Presidential Symposium’ at EHA, which picks a handful of outstanding abstracts, and some updates from our Bloodwise researchers.

Two pronged attack in acute leukaemia

Dr Fang Lui, from the Chengdu Military General Hospital in China is looking at a new CAR-T therapy called ‘CLL1b-CD33b’ that has a two-pronged approach, in that it targets two receptors called CLL-1 and CD33 on the surface of acute myeloid leukaemia (AML) cells. What is interesting about this CAR-T therapy is that the CLL-1 receptor targets leukaemia stem cells - a small, slow growing population of leukaemia cells that are resistant to treatment and give rise to a steady stream of new leukaemia cells. And the CD33 receptor targets the main bulk of AML cells. Dr Lui says that although the two approved CAR-T therapies (for hard to treat forms of aggressive lymphoma and acute lymphoblastic leukaemia [ALL]) are working well, AML is very diverse in terms of genetics and biology, making it prone to treatment resistance and relapse. Having a CAR-T that targets two receptors that are highly expressed in AML hopefully will overcome this.

CAR-T therapy CLL1b-CD33b attacks the tree (bulk of the AML cells) and roots (AML stell cells.

Dr Lui says the treatment could be a ‘bridge’ to stem cell transplant for aggressive, relapsing, hard to treat AML, much like our COLBALT trial in Diffuse large B cell lymphoma (DLBCL). Because they have been concerns about the safety of the treatment, with some patients developing ‘cytokine release syndrome’ which causes flu-like symptoms, and other neurological affects are seen, many CAR-T therapies in development now have a ‘safety switch’. This means doctors can administer an immunotherapy which shuts down the treatment, and CLL1b-CD33b has this built in. A phase I study is planning to recruit 20 people, and is already showing promising results.

New treatment in elderly people with chronic lymphocytic leukaemia

Dr Valentin Goede from The University Hospital, Cologne, Germany presented the 5 year final results of the CLL11 study, which wanted to improve the treatment of elderly people with chronic lymphocytic leukaemia (CLL) who had underlying conditions, such as diabetes. People who have not been previously treated for their CLL are usually given the immunotherapy rituximab plus chemotherapy when they start showing symptoms, but recent clinical trials have shown that another immunotherapy called obinutuzumab might work better than rituximab.

The final results from the CLL11 trial showed that obinutuzumab given with chlorambucil gives a better survival rate than rituximab plus chlorambucil, and appears to be safe and well tolerated. People receiving obinutuzumab were treatment free for around 4.5 years, which was double the time of those being treated with rituximab. These results support using obinutuzumab and chlorambucil as first line treatment for elderly people with CLL and who have underlying conditions.

Is RELEVANCE relevant in follicular lymphoma?

Professor Franck Morschhauser from the Hospital University Centre of Lille, France talked about the RELEVANCE trial. This trial is comparing lenalidomide given with rituximab against rituximab plus chemotherapy, followed by rituximab, in previously untreated follicular lymphoma. First line treatment for people with follicular lymphoma has been rituximab plus chemotherapy, followed by rituximab maintenance. Combination immunotherapy with lenalidomide and rituximab is a chemotherapy-free treatment that has shown promising results in previously untreated patients with follicular lymphoma.

This was a big study, with over 1000 patients recruited. At 3 years, both treatment groups were doing well and had comparable results, with around 77% of people not having a worsening of their disease (progression free survival). But the side effects were different – the rituximab group had lower white blood cell counts (sometimes with fevers), and the lenalidomide group had issues with rashes, diarrhoea, and ‘tumour flare’ where patients can experience a feeling of their disease worsening. 

So what does this study mean? Prof Morschhauser says that a further 2-3 years are needed to confirm the side effects of the treatments, and to see if there is any difference in overall survival because it’s still too early to tell. Information on improvements to patient’s quality of life are yet to be assessed, but lenalidomide has potential. The final results are expected in 2024.

Focus on Bloodwise research: CML – the DESTINY trial, and preventing GvHD in stem cell transplants

Saturday morning was full of Bloodwise funded researchers presenting their latest findings.

Professor Richard Clark from the University of Liverpool presented the final results from the DESTINY trial, which wanted to see if people with chronic myeloid leukaemia (CML) who were doing well on their TKIs could reduce, or even stop their medication. The trial found that around 72% of people were still in remission 2 years after stopping their TKIs, which is fantastic news. And in people who had relapsed, once they went back on their TKI they were able to reach remission within 5 months. Results for DESTINY were far better than other TKI stopping trials, such as EURO-SKI, which is perhaps due to the difference in the dose reduction guidelines.

Although TKIs work well, some people are unable to tolerate them due to the side effects, so being able to reduce or stop these drugs will really help improve life for people living with CML.

Dr Antonio Galleu from Kings College, London, presented further results on optimising treatment for graft-versus host disease (GvHD), a potentially life-threatening complication from stem cell transplants. People with GvHD can be treated by giving an infusion of mesenchymal stem cells (MSCs), which are a rare type of bone marrow cell. But responses have been unpredictable.

Dr Galleu has previously found that if the MSCs are dying, they have more of a therapeutic effect in mice with GvHD. Now he has found out that the killing of MSCs depends on the patient’s immune system, and is figuring out how to group patients for therapy according to their cytotoxic cell characteristics – the cells that are responsible for killing MSCs.

I’ll be posting up a round up blog later this week, so watch this space! And if you want to find out about what I heard at EHA earlier, you can read more here.

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