Dr Jason Chan speaking with Madam Ang Swee Teen, a 69-year-old patient with diffuse large B-cell lymphoma whose cancer has relapsed six times. ST PHOTO: CHONG JUN LIANG

SINGAPORE - Retiree Ang Swee Teen, 69, has seen her cancer relapse six times in nearly 20 years.

She was first diagnosed with follicular lymphoma in December 2006, after finding a lump on the left side of her neck, as well as experiencing other symptoms such as frequent urination.

Scans showed the cancer was in remission after she received 10 sessions of R-CVP chemotherapy, which combines four drugs.

“When I was first diagnosed with cancer, it was very sudden, as my mother had passed away less than a week ago, also from cancer,” said Madam Ang, who previously worked in the publishing industry.

Her cancer later recurred and Madam Ang received chemotherapy again in 2008 and 2011 after discovering lumps in her right leg and neck. Scans later showed the cancer to be in remission. However, after she discovered a lump in her left leg in 2018, a biopsy showed the cancer had become high-grade, double-hit B-cell lymphoma – a rare and aggressive subtype of diffuse large B-cell lymphoma, which typically has a very poor prognosis.

About 300 patients are diagnosed with diffuse large B-cell lymphoma each year in Singapore.

She underwent six sessions of chemotherapy and experienced side effects such as hair loss.

Subsequently, Madam Ang had to undergo treatments such as chemotherapy and radiotherapy after malignant lumps were found in the area of her ribcage on three separate occasions in 2022 and 2023.

“To be honest, I felt discouraged and at times helpless, but I told myself that I have to be strong and move forward to overcome this hurdle,” said the divorcee, who has two adult children.

Madam Ang’s experience with lymphoma, one of the most common cancers in Singapore, highlights the inadequacy of conventional cancer treatments for some patients, and the promise of precision medicine to be more effective for them.

It is not uncommon for cancer to relapse multiple times, said Assistant Professor Jason Chan, director of the Cancer Discovery Hub at the National Cancer Centre Singapore (NCCS).

He noted that this can occur when patients develop resistance to the drugs used to treat them.

More than a third of patients with diffuse large B-cell lymphoma in Singapore relapse or die within five years, according to a study by researchers at NCCS.

The study looked at 1,071 patients diagnosed with diffuse large B-cell lymphoma at NCCS between 2010 and 2022.

It found that 74.7 per cent of those with the cancer survived beyond five years, with 64.5 per cent of all patients remaining in remission at that point and considered to be effectively cured.

While this is consistent with global figures, it means that about 30 to 40 per cent of patients face relapse, said Prof Chan, who is also principal investigator for the study.

The study said this demonstrated that the R-Chop chemotherapy regimen – which comprises five drugs – or similar regimens in managing diffuse large B-cell lymphoma were inadequate.

“This basically highlights the disease burden that still exists in the country and why we need better treatments upfront in that setting,” said Prof Chan.

He pointed to new treatment options approved by the US Food and Drug Administration, reflecting the progress in the advanced treatment options that are effective.

These include novel classes of drugs known as antibody drug conjugates – which target and kill tumour cells while sparing healthy ones – chimeric antigen receptor T-cells (CAR-T), as well as bispecific T-cell engagers (BiTEs).

As at April, two CAR-T therapies and one BiTEs treatment have been approved to treat relapsed lymphoma in Singapore, but they are not on the Cancer Drug List, which includes only clinically proven and cost-effective treatments that can be covered by subsidies, MediShield Life and Integrated Shield Plans.

One antibody drug conjugate, Polatuzumab vedotin, has been approved for the treatment of newly diagnosed lymphoma cases and is included on the Cancer Drug List.

Prof Chan said he is looking forward to more such treatments in the future.

But he cautioned that such therapies may not be suitable for all patients, and that treatments should be personalised according to the needs of individuals in consultation with their doctors.

Madam Ang faced another relapse in December 2023 when she noticed a lump in her left underarm, which grew to the size of half an egg by February.

She was placed that month on BiTEs, the novel form of lymphoma treatment that was recently approved for use here on those whose diffuse large B-cell lymphoma has relapsed multiple times.

Madam Ang is now in remission.

“I think the key takeaway is that aggressive lymphoma can be effectively cured with modern treatment,” said Prof Chan.

However, there still needs to be more research done in the field, as well as greater access to such treatments for patients, in particular those in Singapore, he said.

This is the largest such study on clinical outcomes of diffuse large B-cell lymphoma patients here, with the last such study conducted in 2008 involving just 279 patients.

The patients in the recent study – who were followed up for about two years – had a median age of 63.8 years, with the youngest being just 19.

While the study has not yet been published, its findings were presented at the European Society for Medical Oncology Asia Congress in December 2023.