Bispecific Antibodies: Early Side Effects

Dr. Joe Mikhael: Throughout this series, we've been  exploring a novel way of treating myeloma, using bispecific antibodies or bispecifics.  These remarkable new drugs have two arms, one that hooks onto the myeloma cell and  the other that engages a local immune cell, usually a T-cell, to help destroy the myeloma.  These are highly effective treatments, but like all therapies, they do come with some potential  side effects. In this video, I will review the early side effects or those we typicall

y see  within the first month of starting therapy. Complications can occur right after patients  receive their first dose of a bispecific antibody. I will focus on the two most common  effects. Cytokine release syndrome or CRS, and immune effector cell-associated  neurotoxicity syndrome or ICANS. Cytokine release syndrome. When T-cells are  engaged, the body can have a systemic reaction called cytokine release syndrome or CRS for short.  It's like an overreaction of the immune system to the immu

notherapy given. We classify it grade one  to four or grade 1, 2, 3, and 4, based on the key symptoms and signs of fever and blood pressure.  Grade three and four CRS require admission to hospital in an intensive care unit as patients  need medications to boost their blood pressure. Thankfully, most CRS with bispecifics is grade  one or grade two, and can be managed rapidly, although usually in hospital or  at least an observation unit. CRS typically occurs with the  first few doses of a bispeci

fic. Indeed, most bispecifics will have a step up  dosing strategy to give the patient a very low dose of the drug to reduce the risk of CRS. This  step up dosing may be given over several days, often in a hospital or in a dedicated  observation unit. Some centers may do some of this entirely as an outpatient, so it is  critical that patients and their care partners be aware of the potential side effects so they  can be communicated to the healthcare team. What should patients and their care par

tners  expect early on when receiving a bispecific antibody? Well, most centers will admit their  patients for at least five to seven days, some may even have specialized units. The length  of admission and observation will vary and could be planned for up to two weeks. This, of course,  could even be longer if a patient develops CRS. Most CRS will occur within the first few doses,  and it is often signaled with fever. Approximately 50% of patients will need treatment of that fever.  Options for

treatment include close observation, fluids, a drug called tocilizumab or  toci for short, and steroids. Local institutional practices vary as to when  each of these approaches may be employed. The second side effect we watch carefully for  is a neurological one. Although we see this less commonly than we do with CAR T-cell  therapy, we can see varied and different effects on the neurological system of  a patient, often called neurotoxicity. One in particular we watch for is ICANS or  immune ef

fector cell-associated neurotoxicity syndrome. This side effect can manifest  as really any neurological symptom. Most common ones include difficulty speaking,  tremor, confusion, and even coma. These can become more severe if not treated,  so we are careful to watch for these. Patients and their care partners may be involved  in performing basic testing to monitor for ICANS in the form of the ICE score. Patients may be  asked to walk, write, and answer basic questions to assess their status. Th

ankfully, ICANS occurs  in less than 10% of patients receiving bispecific antibodies and tends to happen in the first few  weeks. The most commonly used treatments include fluids, steroids, and tocilizumab. Importantly,  we are beginning to learn that these effects may also be different based on a person's race  or ethnicity. As we treat more patients and understand these immunotherapies better, we will  have more optimal ways to manage all patients being treated with bispecifics. Looking to the

  future, we may even become more aggressive in trying to prevent CRS and ICANS in the form  of prophylaxis or prevention with drugs like tocilizumab. This is being tested. Now all drugs  in myeloma go through an evolution to maximize their benefit and reduce their toxicity.  We are going through that process now with bispecific antibodies so our patients can have  the greatest benefit and the least side effects.