AE Profile of Bispecific Antibodies Can Be Predictable in Myeloma Management

Management of CRS and ICANS depends on the grade.

Following the first approval in 2022, bispecific antibody therapy has added to the triple- and penta-refractory multiple myeloma treatment landscape. With this, there are adverse events (AEs) that oncology nurses must be aware of following the administration of these agents.

During a recent Community Case Forum event, Donna Catamero, ANP-BC, OCN, CCRC, and colleagues discussed AE monitoring of patients being treated with 1 of the 3 available bispecific antibodies for relapsed/refractory myeloma: elranatamab-bcmm (Elrexfio), talquetamab-tgvs (Talvey), and teclistamab-cqyv (Tecvayli).

“[Adverse events] can be predictable, depending on the drug we’re using,” Catamero, who is the associate director of the Multiple Myeloma Research Program at the Mount Sinai Health System in New York, NY, said. “[Immune effector cell-associated neurotoxicity syndrome (ICANS)] will typically follow a [cytokine release syndrome (CRS)] event, but we know that that can happen at any point. Cytopenia, [hypogammaglobulinemia], and then infections–I think that all goes hand in hand.”

ICANS (commonly referred to as “neurotoxicity”) and CRS are some of the more severe adverse events associated with bispecific antibody treatment. Catamero stressed that providers in the academic setting and the community setting should know how to approach AEs–especially as patients may start treatment in an academic or specialized institution and then move on to the community setting.

“Sometimes there are knowledge gaps, nothing major, because we told them what needs to happen. But we also check on them,” forum attendee, Michelle Lyn, MD, MPH, said during the event.

CRS management depends on the grade:

• Grade 1 can be treated with supportive care; for fever treatment, consider tocilizumab for persistent fever.
• Grade 2 should be treated with intravenous fluids, tocilizumab, and low-dose vasopressor therapy, if needed; or treat with intravenous dexamethasone if there is persisting hypotension.
• Grade 3 requires admission to the intensive care unit (ICU); continuation of tocilizumab and dexamethasone; the addition of anakinra if the condition is unresponsive; consideration of anti-TNF antibodies; or an echocardiogram if hypotension persists.
• Grade 4 should be treated in the ICU with continuation of grade 3 protocol plus intravenous high-dose methylprednisole.

Similarly, ICANS treatment should also be grade-specific:

• Grade 1 should undergo observation, while withholding oral food/medication and opting for intravenous administration; for agitated patients, administer haloperidol or lorazepam; for high-risk patients give high-dose dexamethasone, start non-sedating AEDs, and conduct an MRI of the brain, lumbar puncture, funduscopic exam, and EEG.
• Grade 2 should be treated with dexamethasone every 12 hours, and if that does not improve symptoms, patients should then be treated with a higher dose of the drug (20 mg every 6 hours), given more frequently or an alternate like anakinra or tocilizumab, if they have concurrent CRS.
• Grade 3 protocol changes to the addition of 10 mg of dexamethasone every 6 hours; in addition to grade 2 criteria, if there is increased CSF pressure, use acetazolamide, mannitol, or hypertonic saline.
• Grade 4 should be treated with 20 mg of dexamethasone every 6 hours or high-dose methylprednisolone if the patient is dexamethasone-refractory. If refractory, the consideration of other treatments such as lymphodepletion with cyclophosphamide; consider mechanical ventilation, EEG, and CT-MRI imaging. If CSF pressure is > 20 mm Hg, drain CSF via Ommaya reservoir or cranial or lumbar catheter.

“Anything about the CRS and infections aside, which can be managed, the side effect profile [of bispecific antibody therapy] was actually pretty manageable, especially for people who have been through so much,” forum attendee, Patrick Spencer, RN, OCN, of Mount Sinai said. “They handle it very well, and it’s refreshing for them.”