Dr Rob Henderson
Consultant Haematologist, St. James’ Hospital
Dr Eoghan Molloy
Consultant Haematologist, Cork University Hospital
Patients with difficult-to-treat blood cancers that are not responding to first-line therapies are starting to benefit from new targeted treatments.
Some patients suffering from certain types of blood cancer find their disease progressing even after multiple lines of therapy. Patients who go through the intense toxic effects of treatments like chemotherapy and radiotherapy may find they work initially, but the disease comes back (relapsed) or they do not respond at all (refractory). These tough-to-treat areas include relapsed/refractory blood cancers, such as diffuse large B-cell lymphoma, follicular lymphoma, as well as leukaemia and myeloma. However, recent breakthroughs have led to new treatment options for these patients that harness the body’s own immune system to fight the cancer. One promising example of this kind of treatment is bispecific antibodies.
Bispecific antibodies as effective immunotherapy
The body’s immune system produces antibodies to protect against infections by tagging bacteria and viruses for destruction by immune cells. Bispecific antibodies are engineered by scientists to attack diseased cells, such as cancer cells. Bispecific antibodies have two different targets on the same molecule: one sticks to the blood cancer cells and the other sticks to the patient’s immune cells, thereby binding them together and harnessing the patient’s own immune system to attack the cancer cells.
Dr Robert Henderson, who has experience administering bispecific antibodies to patients at St James Hospital Dublin, insists: “There is encouraging evidence that these drugs work even after a number of lines of therapy have failed, including some complete remissions.”
Treatment process and side effects
Dr Henderson explains: “It’s vital that when patients relapse, we treat them promptly because these diseases can accelerate quite quickly.” Patients are initially administered low doses that are gradually increased in the hospital over the first few days to monitor for side effects. They are then able to go home and continue treatment as outpatients every few weeks.
Patients are monitored for side effects, including inflammatory reactions and neurological side effects. However, Dr Eoghan Molloy, Consultant Haematologist at Cork University Hospital, asserts that the side effects are manageable. “As a doctor treating lymphoma patients, I have witnessed patients achieving a much-improved quality of life, with far fewer side effects than with chemotherapy,” he says.
There is encouraging evidence that these drugs work
Dr Rob Henderson
even after a number of lines of therapy have failed.
Applications to achieve improved remission
Dr Henderson describes the treatment as ‘a great tool’ in fighting blood cancers but says: “More broadly, trials are being conducted to explore whether they work better in earlier phases in fighting diseases. Will they be used earlier on to get people cured without relapsing or needing other therapies later on? Could they work alongside — or instead of — chemotherapy; and will that achieve better remissions?” He hopes that bispecific antibodies could allow more patients to get a remission remission first.
Development of blood cancer treatments
Dr Henderson charts the progress in treating blood cancers over the past 30 years as evidence that progress can be rapid. “In the past, it was chemotherapy regimes alone. Then, monoclonal antibodies — which bind targets on cancer cells and destroy them — were added to regimes and now form the bread and butter for many B-cell lymphoma treatments. Bispecific antibodies represent the next step in this arm of immunotherapy.
“Many relapsed patients ultimately require a bone marrow transplant or CAR-T (chimeric antigen receptor T cells). CAR-T differs from bispecific antibodies, they are genetically engineered to create cells with a receptor that targets cancer cells and kills them. They have shown promising results, however, one challenge is that the engineering part takes a few weeks. Bispecifics can be available immediately and could bridge patients to these therapies”
Access to more treatment options
Bispecific antibodies provide an ‘off-the-shelf’ option that engages the body’s natural defences to recognize and eliminate cancer cells, potentially giving patients with a high risk of relapse access to more treatment options. Furthermore, as researchers continue to explore the use of bispecifics in combination with other drugs, there is hope for improved efficacy for patients throughout the treatment journey.
The primary discussion mentioned in this article is with reference to DLBCL.
M-IE-00001630 September 23