Understanding Cancer and Beyond 2018 — The New Paradigm in Cancer Management
In comparison to breast, lung, colorectal, prostate and liver cancers, blood cancers are relatively rare.
Since the development of radiation therapy in the early 1900s and chemotherapy in the 1940s, cancer researchers have continually sought the most effective ways to treat the different types of cancer.
In blood cancers, particularly liquid tumours such as leukaemia, treatment has generally required systemic chemotherapy. In recent years, however, newly developed targeted forms of therapies are increasingly being used in the treatment of blood cancers.
Blood cancers can be broadly classified into three categories: lymphoma, leukaemia and multiple myeloma.
Lymphoma affects the lymph nodes, liver and spleen, and is the most common blood cancer in Singapore. It is the fifth most common cancer in the male population and the sixth most common cancer in the female population. The incidence rate is increasing at 4 per cent annually; that is, about 2,000 cases every year (or six new cases every day) are being diagnosed.
Leukaemia affects the white blood cells and bone marrow. It is sub-classified into acute and chronic Leukaemia, with a 70 to 80 per cent cure rate for childhood acute leukaemia in children and less than 50 per cent cure rate in adults.
Multiple Myeloma, a cancer of the plasma cells, affects the bone marrow and also commonly the bones and kidneys.
Novel therapies, including immunotherapy and cellular therapy, have yielded very positive results, and are increasingly being utilised as forms of additional therapy particularly for the more aggressive forms of blood cancers.
Hematopoietic stem cell transplantations (HSCT) or bone marrow transplants are early examples of cellular therapy used in treating patients with advanced blood cancers. By replacing the patients’ bone marrow, we aim to replace the defective or ‘diseased’ bone marrow with cells from a healthy matched donor. This gives rise to a healthy functional bone marrow, and at the same time it is hoped that the donor cells will generate an effective immune system to police and destroy and remaining cancer cells.
In the late 1980s, cancer researchers have discovered that the efficacy of the immune system in detecting and fighting specific cells could also be enhanced through the combination of T Cells with “designer” receptors called Chimeric Antigen Receptors (CAR) into CAR-T Cells.
CAR-T cell therapy involves the harvesting of immune cells from a patients’ blood, and then genetically modifying these cells with a receptor which makes them recognise and target the cancer cells better. This therapy helps to create an army of cells that can zero in on cancer cells to destroy them, when injected back into the patient.
In the United States, CAR-T Cell therapies, including Kymriah (Novartis) and Yescarta (Kite), have been approved by the FDA in 2017 to treat certain patients with B-cell acute lymphoblastic leukaemia and non-Hodgkin lymphoma.
Very positive results have been shown in clinical studies on children and adults who are mostly suffering from very aggressive forms of blood cancers, like B-cell ALL, high grade B-cell Lymphoma and multiple myeloma, which are resistant to existing therapies. These patients have demonstrated remission rates of 80 to 90 per cent after being treated with Active Cellular Therapy (Living Drug) Immunotherapy.
These newer approaches in treating blood cancers hold tremendous potential and promise. However, while effective, these treatments still cause significant side-effects in a small but significant number of patients.
Patients can develop severe neurological (brain related) side effects, and some patients can also develop severe multi-organ damage due to the powerful effects of the cancer killing therapy. In addition, this new form of therapy is presently extremely costly with the first licenced products priced at in excess of USD$300,000 per patient.
Despite the potential limitations of access of treatment due to cost and concern on toxicity at present, the clinical success of CAR-T cell therapy will mean that its use will undoubtedly expand over the next few years. Advances in technology will likely aid in the reduction of the cost of CAR-T cell therapy, and newer generations of therapy are being explored to further improve the success rates while limiting the potential side effects.