A NZ trial using immunotherapy to beat a form of blood cancer is expanding after promising results – and it’s hoped the ‘gold standard’ treatment will soon be widely available.
It took just one minute for Peter Jefferies to be infused with a CAR T-cell treatment that saved his life. On August 22, 2022, the now 60-year-old lay in a bed at Wellington Hospital and was given a single shot of his own genetically modified immune cells to fight his deadly lymphoma B.
It was liquid gold for the West Coast police officer, who had endured five rounds of aggressive chemotherapy and was facing palliative care. Without CAR T-cell treatment, his haematologist told him he would die.
Jefferies is one of 16 patients out of 30 who were successfully treated in the first stage of the CAR T-cell therapy trial being run by the Malaghan Institute of Medical Research in Wellington. Others who have publicly shared their stories include Auckland poet Michele Leggott (Listener, April 15, 2023) and Kirsty Horgan of Christchurch.
All those in the clinical trial have been diagnosed terminally ill and have exhausted conventional options to fight non-Hodgkin lymphoma B – a type of blood cancer. Stage II of the trial is now under way, with 60 patients being recruited, and results are expected by mid-2026.
CAR T (chimeric antigen receptor T cell) immunotherapy is a highly specialised treatment in which a patient’s own immune system cells are extracted and modified in the laboratory to recognise and attack cancer cells when injected back into the body.
It’s a one-dose transfusion and it’s a curative treatment, not just one that prolongs life.
Points of difference for the WZTL-002 drug Malaghan is trialling include that it is a one-shot dose and has a better safety profile, with fewer side effects, than Car T-cell therapies available overseas.
In an exciting development for lymphoma B patients here, the trial is this month extending to hospitals in Christchurch and Auckland, making the treatment more accessible to qualifying patients around the country.
Even better, Malaghan’s research has gone so well that its biotech partner, BioOra, aims to open a CAR T-cell manufacturing facility in Christchurch by July next year.
Manufacturing cancer treatments at an international scale will be a first for New Zealand, and the hope is that terminally ill lymphoma patients will no longer have to travel overseas for the potentially life-saving treatment.
BioOra – a partnership between the Malaghan and investment firm Bridge-west Ventures NZ – is the only licensed contract and development manufacturer of CAR T-cell therapeutics in New Zealand. Although the planned facility will initially offer CAR T therapy to only lymphoma B patients deemed suitable to receive it, Malaghan and BioOra hope the immunotherapy may eventually be offered to patients with other types of blood cancer, and in future, even be used to trial and offer immunotherapy treatments for other cancer tumours.
There is, of course, a long way to go with the trial and subsequent approvals will be needed for general release of the drug. But the 56% positive response rate in stage I suggests it is superior to current treatments.
Jefferies was fit and healthy and had never spent a night in hospital when he felt a pain in his shoulder, which after many tests and scans, turned out to be B-cell lymphoma. He talks from his home at Moonlight Creek, near Greymouth, where he lives with his partner, Leanne Coburn, about the most dramatic year of his life.
A tumour the size of a football was attached to his spleen and cancer cells were hurtling through his bloodstream. Six rounds of chemotherapy made him ill and radiation wasn’t an option. The tumour – and his spleen – were eventually cut out. But to get rid of the lymphoma, he abandoned the prospect of a stem cell transplant and wanted to try CAR T-cell therapy. He was lucky to be a successful candidate for the stage I trial, which had a waiting list.
As he went back and forth to Wellington for treatment, he was monitored for a few weeks. A few days after the infusion, he had a few hours of a fever – often a side effect – but that was it.
Jefferies had a PET scan (imaging to check for cancer) and, a month before Christmas 2022, he got the gift he’d been waiting for: his lymphoma had been cured.
“I feel very lucky and so grateful to all the medical staff who saved my life,’’ he says with a quick smile. “It’s amazing stuff – expensive though – and it would be pretty amazing to have it here in New Zealand.
“The difference is that it’s your immune system fighting the cancer, rather than chemotherapy, which is a poison.’’
Big plans
In the Malaghan Institute’s basement, a pressure-tight, filtered laboratory holds two cocoons – small plastic devices filled with a bright pink fluid the sickly shade of dishwashing liquid that will transform a lymphoma B patient’s blood cells into cancer killers.
In another lab, technicians in full PPE are isolating T cells which, in lay terms, are like bullets that can attack cancer cells. These cells have been switched off in a blood cancer patient, causing the disease to multiply through the blood and bone marrow.
Malaghan and Bridgewest formed BioOra in 2021 to progress the clinical trial, and Bridgewest’s John Robson is managing director of the joint venture. It’s now formulating plans for the Christchurch facility, which will – at scale – have the ability to offer up to 3000 CAR T-cell treatments a year.
It has to be commercialised to pay for it, but Robson hopes talks with Pharmac will lead to it being publicly funded.
“It’s curative – no ongoing costs,” he says. “It reduces the impact on the health system from 1-3 years to 1-3 months, which is a massing saving to New Zealand.”
Though the cost per dose is significant, the bill to taxpayers could eventually be offset by medical tourism: in the same way that people go to Thailand for dental treatment, patients from other parts of the globe could come here.
By treating patients in an outpatient setting rather than hospital admission and using automated production, BioOra aims to manufacture the therapies for about a quarter of the cost of those produced overseas. Nevertheless, Robson says the cost per infusion will be “somewhere north of $200,000″.
“The single shot may be expensive but not when you look at the cost of a bone marrow transplant or two, or long-term chemotherapy and radiotherapy.
“It’s a one dose, one- to two-minute transfusion, and it’s a curative treatment, not just one that prolongs life or makes life more comfortable until the inevitable point.”
Last year, BioOra raised $5 million to fund the new facility. It is looking for more investment and hopes to begin building in the second half of this year. Robson will outline the plans at the Cancer Society’s “In Pursuit” 2025 Cancer Research and Innovation Conference in Christchurch on March 6 and 7.
The joint venture plans to manufacture 400 CAR T doses in the first year – more than enough to help the 250 or so patients diagnosed with lymphoma B each year who are deemed eligible. It aims to double production each year to reach 3000, then look at building other facilities. “We might apply to manufacture other immunotherapies, licensed overseas, that would help with profitability,’’ Robson says.
Robson was involved in the Child Cancer Foundation for 15 years, four of them as chair of the national board, and during this time, the treatments didn’t change. The current standard treatments – chemotherapy and radiotherapy – are invasive and have serious side effects.
Scaling up
Malaghan clinical director Dr Robert Weinkove is optimistic about the extension of the phase II trial to Auckland and Christchurch, and the planned manufacturing facility.
But the haematologist also points out that the treatment doesn’t work for everyone; sometimes the cancers grow too quickly for patients to get on the trial, or sometimes the patients are too ill to qualify.
However, speeding up the manufacture of CAR T-cells will allow the treatment to be scaled up. He also sees the potential to push the tech itself further so other types of blood cancer and myeloma could be treated here. Collectively, lymphomas represent the sixth most common malignancy in New Zealand – about 1000 diagnoses a year.
The hope is that the facility would allow New Zealand patients to take part in international trials for other types of cancer. “We’re excited to do new science, but we need to pass it on to commercial partners for widespread availability in the health system, and that’s where BioOra comes in.’’
Much hinges on the outcomes of the stage II trial (due to end about July next year), after which BioOra will have to prove the drug can be made safely. The drug will need medical approvals from Medsafe and other agencies, and Pharmac will need to give the go ahead if it is to be publicly funded for New Zealanders.
But Weinkove says whereas commercial CAR T-cell treatments in Australia, the US and Europe can come with severe side effects, these proved minimal in stage I of the trial. Stage II will allow the treatment to be tested for efficacy and safety with a larger cohort.
The Cancer Society is excited about the prospect of the treatment being offered on New Zealand soil. Chief executive Nicola Coom says it is “a gold standard service’' that has the potential to revolutionise cancer outcomes.
Leukaemia and Blood Cancer New Zealand CEO Tim Edmonds says CAR T-cell therapy is the poster child of increasingly innovative blood cancer treatments, and offering it in New Zealand will be life changing for those deemed eligible.
New Zealanders can apply to Health New Zealand – Te Whatu Ora for funding for high-cost treatment such as CAR T therapy. According to information supplied to Leukaemia and Blood Cancer NZ under the Official Information Act, Health NZ has paid for the cost of the treatment in Australia for four Kiwi patients since 2019, at a cost of $3.89 million.
In some countries, including Australia, the treatment is routinely funded by the government, and Edmonds hopes Pharmac will urgently fund it here if manufacturing begins. “In many cases, what were once terminal diagnoses are becoming chronic or even curable conditions.’’
Mortgaging the house
For many years, New Zealanders have fundraised, mortgaged their homes and exhausted all their savings to go to China, the US, or other destinations for CAR T treatment. Eight years ago, businessman and author David Downs was diagnosed with non-Hodgkin lymphoma and travelled to Boston for CAR T therapy which saved his life.
Another example is Chris Jolly, who would most likely have died four years ago if he hadn’t self-funded a trip to China for the treatment. About the time of his 60th birthday, the now 72-year-old former Taupō tourism operator was diagnosed with multiple myeloma, a type of blood cancer that affects plasma cells in the bone marrow, the second most common blood cancer in the world.
Jolly was given just a few months to live after enduring two stem cell transplants and months of radiation and chemotherapy. He took his first trip to China for CAR T-cell treatment in 2021, which saved his life. He shrugs his shoulders as he talks about how he had to go back last year, in September, for another two rounds.
Though there is no cure for his cancer, the treatment bought him more years. He’s retired now in Ōhope with wife Sue.
He won’t say how much he spent on treatment, partly because he was part of a trial which meant he got a discount. But it was more affordable than getting the treatment in the US or Israel.
His cancer markers are still reducing from his last CAR T treatments. “This is no doubt the future of cancer treatment as we know it. But why do they wait until you’re damned near dead before they do this? You’ve been gobbling up drugs, and taking up hospital beds, and the medical system in New Zealand has spent a lot of money on you. Why wouldn’t you bring in this heavy artillery at the start, and do the CAR T?’’
The Malaghan’s Weinkove says immune therapy is only going to advance. But he adds conventional treatments such as radiotherapy, surgery and chemotherapy are also advancing, along with tablet medicines interrupting cancer cell pathways.
With many immunotherapy trials under way in China and the US, Weinkove talks about the explosion of new developments and the use of AI to find ways to get immune cells to recognise and conquer cancer cells.
“I’m confident that what we’re doing now will be very, very different 20 years from now and we’ll have much more sophisticated ways of modifying the immune system in very targeted ways to get good results.’’
To read more on CAR T-cell treatment, go here.