Liz Burtally
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Exciting news on clinical trials in blood cancer from ASCO Annual Meeting 2018

Liz Burtally
Posted by
07 Jun 2018

Lots of interesting clinical trials results in blood cancer were presented at a meeting held 31 May to 4 June in Chicago.

The American Society of Clinical Oncology (ASCO) meeting recently took place in Chicago. More than 30,000 researchers, clinicians and pharmaceutical companies gathered to share their latest findings and learn from each other.

Lots of exciting results were presented from clinical trials, which are testing new drugs and treatments in people. I thought I would cover a few stories that I found particularly exciting.

Is more better in myeloma treatment?

We’ve come really far in improving the outcomes of people living with myeloma, with 5-year survival rates rising from 10% in the 1970s to nearly 50% today. But although the outlook for myeloma is better, it’s still incurable and comes back after treatment. And when it comes back, it becomes even harder to treat.

At the moment, the usual treatment for myeloma is chemotherapy (lenalidomide) with a steroid (dexamethasone), but many people do not respond to this treatment, or relapse after a time. In the last decade, thankfully, we have seen a raft of new therapies becoming available, and with so many new drugs to work with, researchers are now looking at optimising dosing and combinations, using drugs that attack myeloma cells in different ways.

Myeloma cells: credit KGH

Trials presented at ASCO were looking at combining 3 therapies together:

  • The OPTIMISMM trial - pomalidomide (a targeted drug that stops myeloma cells developing and also encourages the immune system to kill the myeloma cells), bortezomib (a proteasome inhibitor, which allows protein to build up in the myeloma cells), and dexamethasone (dampens down the immune system)
  • A trial of daratumumab (a new monoclonal antibody that attacks myeloma cells), carfilzomib (a proteasome inhibitor) and dexamethasone
  • A trial of venetoclax (a biological therapy that targets a specific cancer protein), carfilzomib and dexamethasone

Each of these combinations looks promising, but the cost could add up if using multiple therapies, which may affect their availability through the NHS.

A trial called ARROW showed that changing the dose of carfilzomib from two times a week to once a week made no difference to the outcome of people with myeloma. This is great news because having to take treatment only once a week is more convenient, and increases the chance of people with myeloma sticking to their treatment schedule. Please speak to your doctor before considering change to your medication, as dosing reduction in this trial was closely supervised and monitored.

CAR-T in myeloma and non Hodgkin lymphoma

CAR-T therapy has been hitting the headlines for some time now, so of course, it was one of the main hot topics at ASCO.

CAR-T therapy is showing lots of promise in a range of different blood cancers, and has been hailed as a ‘game changer’ with regards to its success, giving people who previously only had a few months to live a chance of a cure. The treatment involves taking a patient’s T cells (which form part of the immune system) from their body, modifying them in the laboratory to attack cancer cells, and then are given back to the patient.

T cell: Credit NIAID/NIH

The results of the Bluebird study were presented, which uses a CAR-T therapy called bb2121 to attack a protein on the surface of the myeloma cell called BCMA. The people enrolled in the study were running out of treatment options and had been heavily pretreated, some having received at least 7 or more treatments. Overall, survival was extended for about a year with no significant safety risks. Because the group of people in this trial are far down the treatment journey, CAR-T may not be a cure for them, but the results show that this treatment may give them more precious time.

The TRANSCEND trial showed that a CAR-T therapy called JCAR017, which targets the CD19 receptor on lymphoma cells, looks encouraging for people with aggressive forms of non-Hodgkin lymphoma who have not responded well to other treatments. Patients who have had multiple relapses and had 2-3 prior therapies including stem cell transplants were included in this study. Doctors say that the response rates to the CAR-T therapy were far better than what they would expect with traditional therapies for this hard to treat patient group who have limited treatment options.

A CAR-T therapy called Yescarta is already available in the US for people with DLBCL who have not responded to at least two prior therapies. But now a new trial called ZUMA-7 has been opened, that wants to see if Yescarta helps people at an earlier stages, so is looking at DLBCL that has relapsed or not responded to first-line treatment of chemotherapy and rituximab. ZUMA-7 will test Yescarta against the standard second line treatment of chemotherapy, and stem cell transplant.

You can read more about what these results mean in our recent blog.

Food for macrophages

Some really exciting results were presented around a new drug called Hu5F9-G4, which encourages the immune system to attack cancer cells. Leukaemia and lymphoma cells have a large number of proteins called CD47 on the surface of their cells. CD47 acts as a “don’t eat me” signal, preventing the cancer cells from being swallowed by immune cells called macrophages, which scan the body for any harmful threats.

Macrophage: Credit מקרופאג

Hu5F9-G4 is a monoclonal antibody that strips away CD47 and its “don’t eat me” signal, allowing the macrophages to swallow and kill the cancer cells. When combined with rituximab, Hu5F9-G4 looks promising for people with hard-to-treat diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Early results show that about a third of people with DLBCL and nearly half of people with FL achieved complete response, meaning there was no cancer cells found in scans after treatment. You can find out more about the trial here. Hu5F9-G4 is also being tested in the Bloodwise Camellia trial for people with acute myeloid leukaemia (AML).

The promise of targeted therapies in acute myeloid leukaemia

After 40 years of chemotherapy being standard of care for acute myeloid leukaemia (AML), a flurry of new targeted therapies have been emerging. Four targeted therapies for AML were approved for use in the US in 2017, and two (mylotarg and midostaurin) and have been approved in the UK.

AML cells.

At ASCO, some encouraging results from a trial that is looking at a new targeted AML therapy called ivosedinib were presented. Ivosedinib targets a genetic mutation called IDH1 found in about 6-10% of people with AML. The trial included people with AML who have relapsed or have become resistant to treatment. Because the results were so promising (an average survival of nearly 20 months seen) doctors say that ivosedinib looks set to become the standard treatment for people with AML who have the IDH1 mutation. Ivosedinib is also being tested in the AGILE trial as a first line treatment in people with AML who are newly diagnosed and have not received any other treatment yet.

Unfortunately, as the name suggests, targeted therapies only work in small populations of people with AML who have the specific gene change that the drugs target. In the UK, the targeted drugs mylotarg (a biological drug that targets a protein called CD33 on the surface of cancer cells; only available through clinical trials at the moment) and midostaurin (targets the FLT3 mutation; approved for use in newly diagnosed AML) are the only targeted drugs available. These drugs are given in combination with standard intensive chemotherapy, so this means probably only younger people with AML who can tolerate the harsh chemotherapy, and who have been previously untreated will benefit. The benefits this group are incremental rather than transformational, and its currently unclear if NICE (who approve drugs for use in the UK) will approve funding for mylotarg. So while we are beginning to see change in the way we treat AML, progress is still limited.

Results from the M14-358 trial also showed that venetoclax combined with a less harsh chemotherapy worked well for people aged 65 and over with previously untreated AML, and who could not have standard chemotherapy because they were too frail. Nearly three quarters of the people enrolled achieved complete remission.

Moving towards chemotherapy free treatment

Targeted therapies such as rituximab, ibrutinib and acalabrutinib could begin to replace chemotherapy as first line therapies for people whose blood cancers affect white blood cells called lymphocytes. This includes non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia and chronic lymphocytic leukaemia (CLL). While targeted therapies still come with side effects, they are designed to specifically attack cancer cells leaving healthy cells relatively untouched, so are less toxic than chemotherapy.

Results from the large international trial MURANO were presented, which compared venetoclax plus rituximab to standard treatment of chemotherapy plus rituximab and bendamustine in people with hard to treat CLL. People treated with venetoclax and rituximab achieved deep and durable remission, meaning that no cancer could be detected after treatment. Also presented were early results from the CAPTIVATE trial, which suggests people who have not been treated for their CLL could benefit from venetoclax and ibrutinib treatment. These two trials add to a series of mounting data – including that from the Bloodwise trial CLARITY - that suggests that people with CLL could move away from traditional chemotherapy, which comes with lots of unpleasant side effects.

More hope for people with hard to treat lymphoma

Polatuzumab vedotin is an ‘antibody conjugate drug’, or ADC: an antibody (a protein that can recognise other proteins) linked to chemotherapy. In the case of polatuzumab vedotin, the antibody is directed at a protein called CD79b, which is found on the surface of many B cell non-Hodgkin lymphomas. ADCs have been around for a while, but newer and more effective ADCs are giving some fantastic results in aggressive lymphoma.

Results were presented from the GO29365 trial, which showed that adding polatuzumab vedotin to chemotherapy and rituximab significantly improved response and survival time, for people with hard to treat DLBCL. What was really promising is that the trial included people who were running out of treatment options and were unable to have stem cell transplants. Polatuzumab vedotin is also showing promise other types of lymphoma, including relapsed or hard to treat follicular lymphoma.

New cancer blood test to detect early signs of myeloma and lymphoma

You may have seen some of the media coverage of a simple blood test being developed that can detect some cancers – including myeloma and lymphoma - in their early stages,. The test acts as a ‘liquid biopsy’, and is still in its early stages of development, so we are still a long way off from this being routinely used in the clinic. You can read more about this story in our recent blog

Take home messages for blood cancer

  • Myeloma treatment could be made more effective by using 3 therapies in combination
  • CAR-T therapy continues to impress, with some really exciting results in people with myeloma and aggressive lymphoma who are running out of treatment options
    • Studies are being set up to test if CAR-T therapy works for people earlier on in their blood cancer
  • Targeted therapies are showing promise in AML, but benefits are still small
  • Chemotherapy free treatment looks set to become a possibility in CLL

As always, ASCO this year generated some really interesting discussion, and illustrates how much progress is happening in improving treatments and quality of life for people living with blood cancer. We hope you enjoyed reading about it here.

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