Australian researchers are close to making an exorbitantly expensive life saving immunotherapy treatment cheaper and more accessible to thousands of leukaemia and lymphoma patients whose disease has returned despite having bone marrow transplants.

The treatment involves collecting T-cells from a simple blood draw and then genetically engineering them in a laboratory to produce chimeric antigen receptors (CARs) on their surface.

The engineered CAR T-cells are then infused into the patient.

Back in the patient, the CARs allow the T-cells to specifically target and then eliminate the cancer cells, just as T-cells would normally target and eliminate virus-infected cells.

In some cases the treatments, two of which have just received FDA approval in the US, have led to long remissions.

The new therapy, Yescarta, (Gilead and Kite Pharma), was last week approved for adults with aggressive forms of non-Hodgkin’s lymphoma, who have undergone two regimens of chemotherapy that failed.

Meanwhile Kymriah (Novartis), for the treatment of acute lymphoblastic leukaemia (ALL) in children, was the first ever CAR T-cell therapy to receive FDA approval last month.

“The results have been remarkable in trials overseas – patients with very active leukaemia for instance, who would have no other options, have gone into a complete remission within a month after receiving the CAR T-cells and the majority of those are undetectable by even the most sensitive methods,” said haematologist and cancer researcher Dr Kenneth Micklethwaite at the Westmead Institute – who is leading a trial of a very similar therapy in Australia.

Speaking to the limbic ahead of the HAA 2017 where he will be presenting a session on CAR T-cells Dr Micklethwaite hailed the new cancer therapy as ‘revolutionary’.

“Obviously CAR T-cell therapy in ALL is the success story of the moment but there are a few others coming up, certainly it is looking very good in relapsed refractory lymphoma and there are some new CAR T products that are looking promising in the setting of multiple myeloma which until now has been incurable – controllable but incurable.

“There’s some really exciting work in this area but one of the big problems is that the production of these cells is quite an expensive process.”

“The one-time treatments aren’t cheap”

Published trials overseas have used a viral system to insert the receptors into the cells and stripping away the dangerous components of a virus. The exhaustive process to ensure the altered virus is safe costs hundreds of thousands of dollars.

Kymriah costs $US475, 000 per dose; that does not include any of the other care that’s needed around the drug to keep people alive without their healthy B-cells.

Meanwhile Yescarta would have a slightly lower price, each dose will cost $US373, 000.

Dr Micklethwaite said the exorbitant cost and limited treatment centres in the US means the potentially life saving therapy is beyond the reach of patients in Australia.

But that may be set to change. Researchers at WIMR, led by Dr Micklethwaite, say they are close to trialling a new way of manufacturing the CAR T-cells in Australia that will bypasses the viral delivery and will drastically reduce the cost of the therapy.

The phase I Study, called CARTELL, will test the safety of the WIMR developed CAR T-cells in patients with persistent and relapsed B-cell Leukaemia and Lymphoma who have already undergone stem cell transplantation.

“What we’ve been working on over the last five years is a really simple and inexpensive way of making these CAR t cells using a non viral system of genetic modification … essentially, we take two pieces of DNA and cut and paste the receptor into the DNA,” he said.

“We’ve got a simple and robust process that enables us to make these cells quickly for around $AU10, 000 per patient – a fraction of the cost of the CAR T-cell products just recently approved by the FDA in the US.”

Dr Micklethwaite said about six patients are expected to receive the Australian developed CAR T-cells in a few weeks and a further 14 patients will be recruited for the study.

“If we can provide a less expensive as effective alternative that is locally produced it gives us some degree of control over the process and it will also provide this therapy to patients sooner than otherwise might be possible.”

Based on the team’s pre-clinical data Dr Micklethwaite said he expects to see a similar safety and efficacy profile with CARTELL that is similar to the more expensive viral vector CAR T-cell products trialled overseas.

But the results aren’t guaranteed – it’s still not entirely clear who benefits from the therapy, Dr Micklethwaite said. It also comes with the risk of very serious side effects, he added.

Side effects can be deadly

Researchers will be on alert for side effects seen in trials overseas, including the potentially fatal cytokine release syndrome, in which the T-cells become over activated and release inflammatory chemicals that damage healthy cells.

The treatment can also cause neurotoxicity that damages the nervous system, which can cause confusion, memory loss, convulsions and other cognitive dysfunctions.

“These are not necessarily easy treatment to have – it’s important to note that there have been patients involved in trials overseas that have died from toxicities related to the therapy,” he said.

“There are some toxicities that we are expecting to manage and we’ve been proactive about trying to minimise the incidence of those and also having well defined pathways for management if they do occur.”

Still, he argued that the benefit of CAR T-cell therapy in patients who qualify for the treatment outweighs the risk compared to standard treatment with stem cell transplantation.

“When you look at the kinds of patients who have received the CAR t cells in clinical trials to date the alternative standard therapy is stem cell transplantation – the mortality rate associated with stem cell transplantation for B cell malignancies is higher than what has been seen with CAR T-cells.”

He said that was also true of long-term morbidity rates when comparing stem cell transplantation against CAR T-cell therapy because recurrent infections occur in a large proportion of patients who undergo stem cell transplantation, he told the limbic.

He made the other point that while a ‘reasonable number’ of patients will relapse after stem cell transplantation that doesn’t seem to be the case with CAR T-cell therapy.

The new trial is part of a series of trials conducted by the WIMR researchers, aimed at strengthening immunity to infection in cancer patients receiving chemotherapy and other toxic treatments.

They hope to apply for a second trial using participant’s own T-cells to create the CARs among leukaemia and lymphoma patients who have not responded to chemotherapy.

The CARTELL Study is expected to run for 18 months to two years. Dr Micklethwaite said he expects to report on initial one-month outcomes early next year.