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'Breakthrough’ therapy for the most common type of leukaemia among children approved in Singapore

'Breakthrough’ therapy for the most common type of leukaemia among children approved in Singapore

White blood cells are removed, genetically modified to attack cancer cells and put back into patients, in a treatment that was recently approved in Singapore. (Photo: Novartis)

SINGAPORE: A type of cell therapy for cancer has been approved for use in Singapore, providing another treatment option for patients with certain types of advanced blood cancers which are not in remission despite having gone through other forms of treatment. 

Such patients include children with acute lymphoblastic leukaemia - the most common type of paediatric blood cancer in Singapore - if they fulfil certain criteria.

The new treatment works by removing disease-fighting cells called T cells from patients, genetically engineering them to attack cancer and putting the cells back into them. 

Developed by Swiss pharmaceutical firm Novartis, the therapy is called CAR-T, or chimeric antigen receptor T-cell. It is marketed commercially as Kymriah.

It was approved under Singapore's new cell, tissue and gene therapy products (CTGTP) regulatory framework which came into effect on Mar 1.

Singapore is the first country in Southeast Asia to offer the treatment. 

Explaining how the therapy works, Professor William Hwang, medical director of the National Cancer Centre Singapore said: “Imagine cancer cells as criminals and T cells as policemen. If there are strong, persistent and covert criminals in the city that the policemen cannot get rid of, the CAR-T process is like taking the policemen out, giving them training to recognise all the criminals and returning them to the city to root out the enemies.”

Prof Hwang described it as a "breakthrough".

“It is a major advancement in the emergence of immune-based treatment strategies and is a significant step forward in offering patients life-saving, individualised cancer treatment for blood cancers and disorders,” he said.

The treatment is, however, expensive and there are potentially serious side effects. 


The therapy is approved for children and young adults with advanced blood cancers, in particular, patients aged two to 25 with B-cell acute lymphoblastic leukaemia (ALL) that is resistant and where a relapse has occurred subsequently or post-transplant.

Acute lymphoblastic leukaemia causes most patients to become anaemic and prone to infection. Signs and symptoms include being prone to bruising easily or prolonged bleeding from minor wounds.

Adults who have diffuse large B-cell lymphoma (DLBCL) that is resistant or have relapsed after two or more lines of systemic therapy may also be eligible for the therapy.

Singapore General Hospital (SGH) is the first Kymriah treatment centre to become operational in Southeast Asia, Novartis said. The National University Hospital (NUH) is making the necessary preparations to become a qualified Kymriah treatment centre.

At SingHealth, which includes SGH, there have been a “number of patients” who have received the therapy as part of clinical trials, said Dr Hwang, who is also head of the SingHealth Duke-NUS Cell Therapy Centre and senior consultant for haematology at SGH. 

As the therapy has only been recently approved, fewer than 10 patients have undergone the therapy out of the trial, and they are being monitored, he added.

"All patients who received CAR T therapy for lymphoma at SGH have responded very well to the therapy and are being monitored," he said.

Doctors said the treatment opens up options to patients who are not eligible or who do not respond to current standards of care and are likely to otherwise die from the disease from the lack of alternative treatment options. 

For patients with B-cell ALL who have relapsed or have resistant cancer, fewer than 10 per cent of patients survive for five years, noted Dr Allan Yeoh, head of the Division of Paediatric Haematology and Oncology of the Khoo Teck Puat-National University Children's Medical Institute at NUH.

With the new treatment, several studies have shown "significant improved patient outcomes with durable responses", he added.

"This gives hope to eligible patients, including paediatrics patients, in Singapore and the region who are seeking a different way to try to treat their cancer because previous treatments have not kept their cancer in remission," said Dr Yeoh.

During processing, the modified T cells are grown, washed, formulated and frozen before they are shipped back for infusion. (Photo: Novartis)

Dr Hsieh Wen Son, a medical oncologist at Icon Cancer Centre said that the availability of Kymriah brings a “much-needed” therapy to patients who do not have other therapeutic options. 

“In addition, it opens the door in terms of the infrastructure and expertise for this and other novel cellular therapies for treatment of a variety of cancers,” he said.


While the therapy could be lifesaving, it comes with potentially serious side effects. 

One common side effect is cytokine release syndrome, which also signals that cancerous cells are being eliminated, the doctors said. The syndrome also means that the CAR T-cells are at work, eliminating the cancerous cells.

Symptoms can include high fever and low blood pressure in the days after treatment is given. 

Other side effects include changes in the brain that cause swelling, confusion, seizures or severe headaches.

However, doctors said the side effects can be effectively managed by a trained clinical care team.

Similar to chemotherapy, CAR T-cells can kill off some of the good B cells that help fight infection, so the patient undergoing treatment may be at higher risk for infection, said Dr Hwang, adding that this can be managed. 

“As the patient undergoing treatment would be closely monitored by a clinical care team, these side effects would be managed and symptomatic treatment would be administered,” he said.

More severe symptoms might temporarily affect speech or cause hallucinations or seizures.

“In most cases, symptoms occur within eight weeks of receiving the therapy and resolve within 12 days," Dr Yeoh said. 

According to the Health Sciences Authority's patient education leaflet on the therapy, “very common” side effects that may affect more than one in 10 people include heart, lung, kidney failure and liver injury, usually within 10 days after the treatment.

Other potential side effects are feeling warm, fever, chills, shivering, sore throat or mouth ulcers, which may be signs of an infection.

“Some infections may be life-threatening or fatal,” according to the leaflet.


Dr Hsieh and Dr Colin Phipps Diong, a senior consultant in haematology at the Parkway Cancer Centre, said that the high cost of the treatment would be a significant barrier for patients.

While Novartis did not say how much the one-time treatment is in Singapore, it costs up to US$475,000 (S$635,170) in the United States.

Dr Hwang said that the cost would “depend on the overall treatment that the patient receives for their condition”. 

“Patients may be eligible for financial support from different government subsidies and from various charity funds at SingHealth institutions, such as the NCCS Cancer Fund, which provides financial assistance for patients in need,” he said. 

Similarly, Dr Yeoh said: “We recognise that cancer treatment can be a heavy financial burden, and patients in need may be eligible for financial support under various government assistance schemes."

He added that there is also the NCIS Cancer Fund that caters to patients in need who may require additional support.

Dr Hsieh also said that the “significant side effects” that may occur in some patients can be a limiting factor. 

“Careful consideration of risk and benefit needs to be applied for each patient," added Dr Diong. 

"Patients who have highly active ALL or DLBCL have a high chance of failing CAR-T therapy while at the same time being at high risk of severe treatment complications,” he said.

Source: CNA/ja(gs)


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