Clinicians are struggling to understand why the therapy is not more widely sought-after in Australia.
CAR T-cell therapy is an approved therapy in Australia and a proven valuable treatment for hard-to-treat and relapsed patients with certain forms of leukaemia and lymphoma.
But clinicians are perplexed about the relatively low uptake, especially given the fact it is available in every state except South Australia, Tasmania, the Northern Territory and the ACT. Even those states and territories where there are no dedicated services, patients can still access the fully funded treatment through established referral processes.
“The demand is not anywhere near what we expected,” said haematologist Professor Simon Harrison, director of the Centre of Excellence in Cellular Immunotherapy at Peter Mac in Melbourne, a centre which has pioneered the therapy and research for more than a decade.
“I think it’s partly awareness and that people might not really understand it. But as a standard of care funded by the government, it’s a little puzzling as to why the uptake is not higher.”
In addition to the approved uses, early studies are underway at Pater Mac looking at using CAR T-cell therapy as a treatment for solid cancers.
“Solid tumors are still a way off,” Professor Harrison said. “But we are working hard to identify malignant and other diseases that can benefit from this exciting technology.”
Trials are currently running in renal cell, and cancers expressing the Lewis Y and NY-ESO antigens. Professor Harrison said the challenges were: identifying suitable cancer specific antigens that have no expression on normal tissues to avoid severe “on target off tumour effects”; getting the CAR T-cells to penetrate the tumour; and stopping the CAR-T cells being “turned off” (suppressed) by the tumour micro-environment.
The revelation comes as one of the first longitudinal study of two patients with chronic lymphocytic leukaemia (CLL) – not an approved indication in Australia – revealed CAR T-cell therapy kept them disease-free for 10 years. While it is a small number, experts say the results are encouraging. And they hope news of the research, published in Nature, will raise much-needed awareness of the therapy.
CAR T-cell therapy is a form of immunotherapy that uses specially altered T-cells to directly and precisely target cancer cells. After a small portion of a patient’s own T-cells has been collected from the blood, these cells are re-engineered in a laboratory to carry special structures called chimeric antigen receptors (CARs) on their surface.
When these CAR T-cells are infused back into the patient, they multiply rapidly, and the engineered receptors may help the T-cells to identify and attack cancer cells throughout the body.
CAR T-cell therapy has been shown to be effective in B-cell acute lymphoblastic leukaemia (ALL) and adult diffuse large B-cell lymphoma (DLBCL).
The treatment currently has TGA and MSAC approval for paediatric and young adult patients up to 25 years of age who have refractory B-cell precursor acute lymphoblastic leukaemia, in relapse post-transplant, or in second or later relapse; and for the treatment of adult patients with relapsed or refractory diffuse large B cell lymphoma after two or more lines of systemic therapy. Approval for its use in myeloma is also expected by early next year.
CAR T-cell therapy is not designed to replace allogeneic stem cell transplant but may replace autologous stem cell transplant for proven indications over the next five years.
In the Nature article, the authors said the long-term effects of this treatment were largely unknown.
They followed two patients with CLL who received CAR T-cell therapy as part of a Phase 1 trial in 2010. Both patients achieved complete remission in that year.
“Ten years later, the CAR T-cells remained detectable, and a highly activated population of cells has emerged which continued to demonstrate tumour-cell-killing characteristics,” they wrote.” Both patients remain cancer free … These cases represent long-lasting CAR T-cell responses and provide insights into how long the treatment effects may last.”
The authors observed an evolution of the CAR T-cells over time, with a highly activated population emerging and becoming dominant in both patients.
“These cells continued to demonstrate tumour-cell-killing characteristics and ongoing proliferation. These findings help us to understand the CAR T cell characteristics associated with anti-cancer response and long-term remission in leukaemia,” the authors concluded.
Professor Harrison said the study, although small, was significant as it showed that persistence was key to achieving long-term outcomes for patients.
What also made it interesting was the fact that CAR T-cell therapy has not proved to be well-suited to CLL at this stage, but these findings may help address how the cells could be re-engineered for lasting results.
“The 10-year persistence of memory is a fascinating finding,” he said.
Professor Harrison said CAR T-cell therapy had plenty of advantages, including the fact it was a one-off infusion with proven long-lasting efficacy.
It does come at a high cost though. While he would not be drawn on the total cost of care for each patient’s therapy course, sources have put it at more than $500,000.
And it is not without risk. There is a risk of cytokine release syndrome in the days following infusion; neurotoxicity in the week after infusion; and infection can occur during or after the therapy.
To be eligible for therapy, patients need to be fairly fit and relatively well. A national patient prioritisation committee meets every week to review all referrals and confirming eligibility for CAR T-cell therapy.
Professor Harrison, who heads the committee, said it had a strong mandate to ensure everyone who fit the criteria could access the therapy, no matter where they live. And centres have the capacity to take more patients right now.
“The data suggests that this is better than traditional treatments for patients who meet the criteria,” he said.