This story was first published in Singapore Health, May-Jun 2016 issue.
 
For patients suffering from peripheral T-cell lymphoma or PTCL, a rare type of the cancer that starts in the lymphatic system, a relapse almost always has a grim prognosis.
 
However, a multicentre phase II trial led by Singapore General Hospital (SGH) that uses a combination of two drugs not usually prescribed for PTCL is offering these patients fresh hope.
 
“We decided to combine panobinostat and bortezomib to treat this group of patients as studies have suggested that both drugs work very well together,” said Associate Professor Goh Yeow Tee, Senior Consultant, Department of Haematology, SGH, and senior author of the study.
 
“This is the first time that a two non-chemotherapy drug combination has been shown to be useful in treating this very difficult disease.”
- Dr Darryl Tan, lead author of the study and Visiting Consultant, Department of Haematology, SGH
 
Usually, when PTCL recurs, the standard treatment is to prescribe one of several approved chemotherapy drugs. But, few patients respond to the treatment as their tumours did not shrink by at least half.
 
“The response rate of patients with relapsed PTCL is extremely poor – a very modest 25-29 per cent,” said Dr Darryl Tan, lead author of the study and Visiting Consultant, Department of Haematology, SGH.
 
But with the trial treatment, over 40 per cent of the PTCL patients involved responded to the panobinostat and bortezomib drug combination. More significantly, half of them no longer had signs of cancer after the treatment.
 
“This is the first time that a two non-chemotherapy drug combination has been shown to be useful in treating this very difficult disease,” said Dr Tan, who is in private practice.
 
The study was done at five tertiary hospitals in Singapore, Malaysia and South Korea between 2009 and 2013, with 25 participants aged 35 to 79.
 
Most were in stage III or IV of the disease and were no longer responding to current standards of care. The small number of participants was due in part to the rarity of the disease. Many also could not start treatment because they had become too sick.
 
In Singapore, close to 700 people are diagnosed with lymphoma each year.
 
At the time of the trial, bortezomib was an approved drug used to treat multiple myeloma, another type of cancer, but not PTCL. Panobinostat, meanwhile, was a new drug that had yet to receive the approval of the US Food and Drug Administration (FDA).
 
Not only did more patients respond to the treatment, they also survived longer. This allowed five of them to undergo “curative stem-cell transplant, which was not an option for them previously,” said Prof Goh.
 
The trial found that patients had a prolonged survival of 10 months on average, and that progression of the disease was delayed by about three months.
 
The drugs did bring on side effects such as dehydration, fatigue and diarrhoea. “But those side effects were nowhere as severe as those experienced when undergoing chemotherapy, and are tolerable even for older patients,” said Prof Goh, noting that their oldest patient was nearly 80.
 
The findings of the study were published in the prestigious medical journal The Lancet last July, and presented at a meeting of the American Society of Hematology (ASH).
 
Because many newer drugs and agents have become available since the trial started in 2008, the team is planning to look at other drugs and drug combinations, as well as dosages, with the aim of making treatment more tolerable and durable.
 
At the same time, biomarker samples from the trial will be analysed to find out, if any, their correlation with the clinical responses.
 
Lymphoma, in its many forms, occurs most often in people in their 60s or older. PTCL accounts for 10-15 per cent of all non-Hodgkin lymphomas worldwide.
 
But in some parts of Asia, the incidence of this rare and aggressive cancer is a higher 20-25 per cent. In Singapore, close to 700 people are diagnosed with lymphoma each year.
 
New drugs have improved the survival prospects of lymphoma patients in general, but not for PTCL patients who often don’t respond to conventional treatment after a relapse.
 
For patients who undergo conventional treatment for the disease, including chemotherapy and stem cell transplant, less than 30 per cent are alive three years after. And at the 10-year mark, the survival rate is under 10 per cent.