Dr. Joseph Mikahel: What are some benefits of bispecific antibody therapy? Well, there are many potential benefits of this kind of therapy. Number one, as opposed to CAR T-cell therapy, these drugs are given directly off the shelf to the patient without the need of pre-collecting T-cells. Number two, because there is no need for T-cell collection, the process is much quicker as these drugs can be given to patients immediately. Number three, scientifically they employ both immune system processes of cellular and humoral immunity, which means they engage immune cells to kill the myeloma, but also engage the antibody system in the immune system to destroy the myeloma cell. Because bispecifics attached to both the myeloma cell and a local immune cell, that immune cell can be activated to kill the myeloma. There is a potential for these agents to engage different kinds of immune cells, and sometimes we may use T-cell engagers or natural killer cell engagers.
Number five, they can also be made to recognize different antigens on the surface of multiple myeloma. Although we naturally think of the BCMA antigen, others are now being developed to target antigens such as GPRC5D and FCRH5. Number six, bispecifics are proving to be highly effective with response rates of over 60% in patients who have been already heavily treated with multiple lines of therapy. Number seven, bispecifics are mostly given in the skin with a short injection, although there are some that still may be given intravenously. Number eight, currently bispecifics are being given as monotherapy, and after a few doses, they no longer even require steroids to be given with them. This can be very attractive to patients as we know steroids can be challenging.
What are the potential side effects of bispecifics? As with any therapy, there are considerable risks and side effects of bispecific antibodies. These can be divided into short term and long term effects. In the short term, this treatment can overwhelm the immune system cause it to almost overreact, especially in the first two treatments, causing what we call CRS or cytokine release syndrome. This can be manifested in many ways, such as fever, confusion, low blood pressure, and other complications. This may require intense monitoring and treatment, and this is why most patients are admitted to hospital for at least the first one or two treatments of a bispecific antibody. Other short-term effects include neurological complications like confusion or neuropathy. Most often these side effects are predictable, short lasting, and are managed by the healthcare team during the first few treatments. After the first few doses, the drugs are given in the outpatient setting.
In the longer term, one of the greatest risks is the development of infections. These can be severe as patients' immune systems are already compromised by their multiple myeloma in addition to the treatment they're receiving. Patients may need antibiotics, supplementary immunoglobulin or IVIG and certain vaccinations along with being monitored closely by their healthcare team. Patients who experience these side effects should always communicate this to their provider. As we develop newer bispecific antibodies, we are also discovering newer side effects that include change in taste, hair loss, nail changes, and several other effects, so it really depends on the individual bispecific therapy that we're using.
