Leader in lymphoma bolsters Monash’s blood cancer research

When haematologist Professor Constantine (Con) Tam joined the Central Clinical School and The Alfred last month he brought with him a wealth of expertise in blood cancers, some Australia-firsts in treatments for them and a new vision for Monash University.

Professor Tam was recruited to become the inaugural Head of the Lymphoma Service at Alfred, a unit that will push the boundaries of treatment for the diverse forms of the disease.

According to the Cancer Council, lymphoma are the sixth most common form of cancer overall (excluding non-melanoma skin cancer).

“The Alfred has always treated lymphoma as a part of its malignant haematology service but what we wanted was to have a program of excellence for lymphoma; the latest protocols and latest therapies, bringing in new research into the precinct, and integrating cutting edge technologies such as CAR- t-cell therapy – expanding the clinical research portfolio for lymphoma,” Professor Tam said. CAR-T cell (Chimeric antigen receptor) therapy is an emerging form of immunotherapy that engineers a patient’s immune T cells to attack cancer cells.

“It’s a really exciting time to set up and run a program from the ground up in a way I think it should be done – to start and mould a newly formed program based on my personal experience at some of the premier cancer centres in the world,” he said.

“The Alfred and Monash has huge potential. It’s got a very large patient population and a stellar reputation for clinical care.”

The unit is also establishing a tissue bank to collect specimens from patients. It has about 10 members doing some work into lymphoma currently and will become a core group of five specialists including a lymphoma nurse, lymphoma fellow and Car-T cell fellow.

“Professor Con Tam is very highly regarded internationally in the area of lymphoma," Professor Nandurkar said. "Con has been the lead author on several innovative clinical trials that have given us much improved options for the treatment of lymphoproliferative conditions. We are excited to work with Con at Alfred Health and Monash University,” he said.

Lymphoma research is a growing area, Professor Tam said. “There’s been an explosion in the number of therapies for the whole group of diseases including new targeted drugs combinations.”

Professor Tam is bringing in a number of new clinical trials with industry into Monash, including targeted drugs and antibody therapies.

He is currently the international principal investigator on seven new drugs. One is a more potent version of the highly successful anti-cancer drug venetoclax, he said. Another new project uses a new technology (PROTAC) to destroy an enzyme called BTK (Bruton tyrosine kinase), a protein that is a regulator of cell growth and survival in various B-cell lymphomas and CLL (chronic lymphocytic leukaemia).

Professor Tam was instrumental in bringing the BTK inhibitor ibrutinib into Australia after hearing about its successful effects at an international meeting in San Diego in 2011. “We went straight up to the podium and said we wanted to see it brought here, so Australia joined the program of development of that drug,” he said. “I was very excited to jump on that global movement very early. Now BTK inhibitors are standard treatment for CLL, mantle cell lymphoma and Waldenstrom Macroglobulinemia round the world.”

Other groups recognised his action and invited Professor Tam to develop second-generation BTK inhibitors. He later led a Phase 1 study into BGB-3111 (zanubrutinib) with patients in Melbourne, taking that inhibitor through to international licensing studies worldwide. “That was a real personal satisfaction to watch that drug go from test-tube to first in-human trial all the way to registration,” he said. “It’s an absolute blockbuster for the company, BeiGene, now.”

The drug, taken as a small tablet, interrupts the pathway of the cancer cells in patients with blood cancers including CLL and non-Hodgkin lymphomas. It’s given to patients who develop resistance to chemotherapy who would otherwise die of resistant cancer.

“There are very few side-effects, and the effects are dramatic,” Professor Tam said. “Some of my patients called me after having their first tablet during the trial – four hours later when they were driving home – saying ‘for the first time in my life my lymph gland feels softer’,” he said. “After two weeks their very large glands were completely gone and blood counts returned to normal. The drug is a real miracle.

“Patients have lived normal lives for the past eight years when they should have died seven-and-a-half years ago,” he said.

Professor Tam designed and conducted the first global study to combine ibrutinib and venetoclax.

Another career highlight came in 2015 when he was invited to become the principal investigator in Australia for the study of Tisagenlecleucel in diffuse large B-cell lymphoma. The Therapeutic Goods Administration (TGA) approved the use of Kymriah® (tisagenlecleucel) CAR T-cell therapy in paediatric and young adult patients mostly with relapsed disease in 2020 – the first CAR-T therapy approved in Australia. Now it is publicly funded, and CAR T-cell is now standard treatment in centres around Australia.

“We are currently in advanced discussions about bringing into the clinic a whole suite of bi- and tri-specific antibodies, which tag the lymphoma with one arm and tag the T cell with the other arm to it, essentially forcibly dragging the immune cell to the cancer – and that has been very effective,” Professor Tam said.

“We’ve had some discussions about the first-in-line to develop some second and third generation bi- and tri-specific antibodies. And we’ve got a CAR T-cell program working with new CAR-T therapies from several companies.”

Professor Tam’s passion for researching new treatments for blood cancers extends back to his early working life as a Haematology registrar. “I was really interested in haematology because of its ability to cure cancer,” he said. “It was also the era of targeted therapy, a very exciting time to be treating cancer patients, when you could design a molecule around particular genetic characteristics and get very good outcomes with almost no toxicity.”

He was chosen as a recipient of a fellowship at the MD Anderson Cancer Center in Houston, Texas, US, at the end of his advanced training in haematology. “It’s the biggest cancer centre in the world,” he said. “It really exposed me to the top leaders, the top doctors in, basically, every disease known to man, the way they think, the way they analyse data and design studies.”

He said his research and clinical practice are intertwined. “My patients are my ‘lab’ – I don’t have a lab that’s separate from them.

“I deliver the best care possible to my patients and treat all those cases with new drugs.”

Prior to moving to The Alfred, Professor Tam served as Disease Group Lead for Low Grade Lymphoma and CLL at Peter MacCallum Cancer Centre and Royal Melbourne Hospital for more than 10 years. He is also past Director of Haematology at St Vincent's Hospital.

Among his publications are 240 peer-reviewed papers in ‘New England Journal of Medicine’, ‘Lancet’, ‘Journal of Clinical Oncology’, ‘Blood’ and other top-tier journals. His work has been cited more than 17,000 times in scientific literature.