Liz Burtally
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Bloodwise researchers present exciting new research at international haematology

Liz Burtally
Posted by
08 Dec 2016

The biggest international haematology meeting took place at the weekend, and many of our Bloodwise researchers were there. Find out what they had to say.

What is ASH all about?

This weekend, the annual conference of the American Society of Hematology (ASH) took place in sunny San Diego, California. More than 20,000 haematology experts from around the world gathered to present exciting new research, and shared ideas on how these findings can be transformed into improving the outlook for patients with blood cancer, and other blood disorders.

Some of our Bloodwise researchers talked about their findings at ASH, and below is a quick summary on what was presented.

Finding the right combination therapies in CLL and AML

Chronic lymphocytic leukaemia (CLL) is characterised by a build-up of faulty versions of white blood cells called B cells in the bone marrow and the blood, crowding out the healthy B cells and other blood cells. Ibrutinib is a new targeted drug that is already showing great promise in patients with CLL, as demonstrated in our IciCLLe trial, which is part of our Trial Acceleration Programme (TAP). But some patients will experience side-effects, or start to become resistant to ibrutinib after prolonged treatment.

In the IciCLLe extension study, researchers wanted to know if patients with CLL who hadn’t responded well on ibrutinib, would benefit more if they also received another targeted drug called obinutuzumab. Patients who hadn’t received ibrutinib were also included. Dr Andy Rawston from St James’s Institute of Oncology in Leeds presented the first results from the IciCLLe extension trial, which assessed 17 patients with CLL who had received combination therapy for one month.

Healthy B cell. Credit: Wellcome Images.

Results suggest that adding obinutuzumab to ibrutinib can lead to big drops in CLL cells in the bone marrow and blood after just one month of treatment. Researchers found numbers of CLL cells in the bone marrow of patients receiving the combination treatment were reduced by 20% compared with no change seen in patients treated with ibrutinib alone who were on the original iciCLLe trial. Also, the B cell count in patients’ circulating blood was an average of 35% of pre-treatment levels compared with average levels of 215% in patients after a month of ibrutinib treatment alone. Combination treatment appeared to be safe and patients could withstand the treatment. These early results look promising for patients with CLL who aren’t doing well on ibrutinib, and we will be watching the progress of the trial closely, so come back again for further updates.

Keeping along the lines of combination treatment to tackle ibrutinib resistance, Dr Sara Farag from the St James University Hospital in Leeds, presented research that is linked to another one of our TAP trials called CLARITY, in which patients with CLL are receiving ibrutinib with the targeted drug venetoclax.

Chronic lymphoblastic leukaemia. Credit: Professor Erhabor Osaro.

Dr Farag wants to understand the molecular mechanisms in cells that lead to ibrutinib resistance in CLL. Using lymphoma cells in the lab, she found that the most common mechanisms of resistance to ibrutinib was the increased activity in B-cell receptor signalling that promotes the growth of CLL cells, and also an elevated production of the ‘pro-survival’ protein BCL2, which causes the cell to resist shut-down. Combining ibrutinib with venetoclax, which blocks BCL2, may help in overcoming resistance to ibrutinib in patients with CLL.

Professor Charles Craddock from the University of Birmingham presented the findings from one of our TAP trials called RAvVa, which tested azacitidine and vorinostat in people who can’t have intensive treatment for acute myeloid leukaemia (AML) or high risk myelodysplastic syndrome (MDS). Although the chemotherapy azacitdine is already used to treat people with AML who can’t have intensive treatment, patients inevitably relapse, or experience just a modest response. Vorinostat is a type of biological therapy that blocks cancer growth, and earlier studies have shown that it can improve the activity of azacitdine.

Professor Charlie Craddock talks about the RaVVa trial at ASH.

After six months of treatment, researchers saw that patients didn’t respond better to azacitidine when given vorinostat. Even though these trial results aren’t what were expected, trials with negative results really matter because they tell us what doesn’t work in a particular patient population — which can be as important as knowing what does. We hope that patients would be comforted by the idea that contributing to a trial, regardless of how it turns out, is really important.

Overtreating patients with CML

Professor Mhairi Copland from the University of Glasgow talked about the Bloodwise DESTINY trial. Outlook for chronic myeloid leukaemia (CML) has been transformed by the development of targeted drugs, known as tyrosine kinase inhibitors (TKIs). But these drugs are thought to control the disease, rather than cure it, so patients currently have to stay on treatment long term. Some patients eventually stop responding to a TKI so then need to find another that works, and many patients experience substantial side effects while on treatment. This trial investigated whether some patients with excellent responses to these targeted drugs can remain well on either a lower dose of treatment or without treatment at all.

Professor Mhairi Copland presents the DESTINY trial results at ASH.

Results from the study suggest many CML patients with excellent responses may be able to safely reduce TKI side effects by cutting their dose in half. Of 174 study participants, the vast majority (93%) showed no evidence of leukaemia relapse one year after cutting their TKI dose. Many patients experienced a significant decrease in TKI-associated side effects within the first three months. Just 12 participants showed signs of leukaemia relapse, all of whom regained their initial remission level or better within four months of resuming a full TKI dose.

Taken together, these findings indicate that many patients with stable CML are being over-treated. Reducing the TKI dose by half appears safe, and is associated with improvements in TKI-related side effects.

New immunotherapy shows promise in myeloma

Dr Lydia Lee from University College London presented her work on testing a new immune-based treatment that directs patients’ immune cells to kill myeloma cells.

T-cell therapy relies on giving patients high doses of T-cells that have been engineered in the lab to possess different receptors than normal, which can recognise their specific cancer, stimulating the immune response back to life. Successful outcomes of T-cell therapy arise because many cancers have unusual proteins on their surface and so engineering artificial receptors is a useful way of targeting these cancer-specific markers. She talked about using T-cell therapy to target two proteins called BCMA and TACI, which are found on multiple myeloma cells.

Multiple myeloma cells from bone marrow. Credit: KGH.

Researchers used chimeric antigen receptors (CARs) on T cells, in which surface receptors were modified into shapes that specifically bind BCMA and TACI. They also attached another protein called APRIL, which is highly attracted to binding to BCMA and TACI, creating a specific immune-based therapy called APRIL CAR.

Using multiple myeloma samples from 50 patients, APRIL CAR efficiently killed cells grown in the lab that expressed BCMA or TACI. APRIL CAR also completely eliminated multiple myeloma in mice without any signs of toxicity. Although this is very early work, researchers hope that by targeting two antigens, APRIL CAR could offer the potential to treat a wider range of multiple myeloma patients. We very much look forward to following the progress of this exciting new approach in tackling multiple myeloma, which is currently incurable.

Preventing CNS relapse in lymphoma

Some lymphomas can invade the central nervous system (CNS), which is made up of the brain, the spinal cord and the nerves to the eyes. Unfortunately, relapse of lymphoma that is found in the CNS is fatal in most patients.

Dr Elizabeth Phillips from University College, London, has analysed data from one of our trials called HOVON 127 BL, which is looking at chemotherapy and rituximab for people with diffuse large B cell lymphoma or Burkitt lymphoma. Patients were treated with chemotherapy combination, and received either one cycle of R-CODOX-M, and then one cycle of R-IVAC, or they received three cycles of DA-EPOCH-R. Dr Phillips was interested in the patients who received cytarabine – found in the R-IVAC chemotherapy – which should stop the lymphoma spreading to the CNS.

Dr Phillips analysed 108 patients from the trial, eight of whom had signs of lymphoma spreading to the CNS. Of these, five (62.5%) were alive with no signs of their lymphoma spreading to the CNS when followed up over two years later. Although the patient numbers were very small, the results are promising. Dr Phillips now hopes to carry out the analysis in a bigger group of patients.

Remembering Professor David Grimwade

On Sunday, Dr Richard Dillon from King’s College London accepted an Exemplary Service Award on behalf of Professor David Grimwade, who sadly passed away this year.

Remember Professor David Grimwade at ASH.

The Exemplary Service Award recognises Prof Grimwade’s creative and untiring service to two blood cancer initiatives. One was The International Consortium on Acute Leukemia (ICAL) – an international network that seeks to improve the care of patients with acute leukaemia, and the other was the Translational Research Training in Hematology (TRTH), which provides junior researchers with a unique, year-long training and mentoring experience. His contributions to both programmes have made a huge impact around the world.

Our Director of Research, Dr Alasdair Rankin who was at ASH, said: “Professor Grimwade was a great man whose work we are proud to have supported, and is sadly missed by all of us. It was wonderful to see him honoured for his fantastic efforts in accelerating blood cancer research and improving the care of patients. We know he meant a lot to the many patients and supporters whose lives he touched. His colleagues are continuing his groundbreaking work at King’s College London, and he leaves a resounding legacy in that his research will go on changing lives for many affected by AML.”

Professor David Grimwade.

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