Long-Term Monitoring for CRS and AEs With Bispecific Therapy
Long-term considerations for the detection and treatment of CRS and other adverse events when managing patients with multiple myeloma.
Transcript:
Cesar Rodriguez, MD: Once we’re done with the step-up dosing and the patient is already on the full dose [of teclistamab], at Mount Sinai [Hospital], we discharge the patient and they can continue their weekly dosing in the clinic. This merges with what the Mayo Clinic is doing. Franny, I’d like your input on discharge. When the patient is being discharged from the hospital, we already have approval for outpatient treatment for teclistamab. The patient is still at risk of CRS [cytokine release syndrome], but it’s less likely. How do you evaluate, manage, and monitor for CRS once the patient is under weekly doses in the clinic?
Frances A. Bell, NP: We’ll usually see the patient on day 8 for their first outpatient weekly dose. In terms of monitoring, either the NP [nurse practitioner] or the provider will see the patient. They’ll usually check their labs—CRP [C-reactive protein] and ferritin—for monitoring. With CRS, we [check that] every visit, along with their vital signs. We haven’t seen much CRS after the first inpatient week. Along with the infusion nurse, when they’re in the infusion center, we’ll go through CRS and ICANS [immune effector cell-associated neurotoxicity syndrome] screening tools with them before they get the dose to discuss symptoms and how they’re feeling.
Cesar Rodriguez, MD: At Sinai, once they get discharged, for the first dose that’s going to be in the clinic, we make sure the patient is being seen and evaluated by a physician and an NP to ensure that there was no CRS from the time of discharge till day 8. From there, the patient is seen at the beginning of each cycle by a physician. They’re evaluated by a nurse or APP [advanced practice provider] with each dose, and they have their ICE [Immune Effector Cell-Associated Encephalopathy] score performed. We’ve been focusing a lot on CRS and ICANS because those are the biggest of the new adverse effects that we didn’t have to deal with in myeloma until now. It’s a new adverse effect, so we need to learn how to treat and manage it. But we can’t ignore the other adverse effects that we’re seeing with bispecifics and other immunotherapies. Franny, what is Mount Sinai doing to mitigate other adverse effects, like infections or reactivation of viruses?
Frances A. Bell, NP: Typically, along with the approval of teclistamab, we’re putting in for insurance authorization and approval for IVIg [intravenous immunoglobulin] for infection prophylaxis. This starts within or by the second cycle of teclistamab. If it’s not approved, we may need to do a peer-to-peer to get it approved. Like all BCMA agents, IVIg is used to prevent infection and is important.
Cesar Rodriguez, MD: On that note, IVIg is a very good topic that I want to elaborate on. In terms of infection, 63% of patients with teclistamab have reported infections. Of those, 35% have had a grade 3/4 infection, which is a significant number of infections. Up to 75% of the patients who received teclistamab are going to become hypogammaglobulinemia anemic if they’re not already hypogammaglobulinemia anemic from prior therapies. The idea of giving IVIg to try to reduce this risk of infections is important. It’s a new concept. We’re used to giving IVIg in patients who were hypogammaglobulinemia anemic and had frequent infections. We’ve taken it a step further. Instead of waiting for the shoe to drop and using it for patients who have more than 2 infections a year, we’re doing it in all patients who receive BCMA. Unlike other agents, like daratumumab, that could also cause hypogammaglobulinemia anemia, the risk of infections isn’t as increased as it is with BCMA-directed therapy. The majority of insurances allow it. However, some require peer-to-peer. Scottand Kirollos, are you doing IVIg prophylaxis? How are you managing IVIg to try to mitigate the risk of infections?
Kirollos S. Hanna, PharmD, BCPS, BCOP: We’re not. We’re utilizing infectious prophylaxis. A lot of the patients who come to us are already on infectious prophylaxis from a maintenance perspective. If they’re not, many of my providers who are certified like to initiate some type of acyclovir or Bactrim prophylaxis. Many of these patients have already been on these prophylactic measures for a very long time. We aren’t doing anything around IVIg unless they are present with recurrent infections. Unfortunately, we’ve seen some of these patients present with infections. Scott, are you doing anything differently in terms of the IVIg?
Scott A. Soefje, PharmD, MBA, BCOP, FCCP, FHOPA: Yes, we’re using it. We wait till the patient becomes hypogammaglobulinemia anemic and then start it, vs starting it up front automatically. We’re measuring those levels and watching them come down. If we see them trending down and coming down, we’ll start it. We do all the prophylactic antibiotics, antivirals, and fungal. All of those go out.
Cesar Rodriguez, MD: That’s a good point because there isn’t any guideline on what we should do with IVIg in this setting. It’s not cheap, and it can have some adverse effects. This is another financial burden to add on to the equation of medications, hospital stay, hotel, or transportation. We definitely need to find a way of reducing the risk of infections because it’s approved for patients who are heavily pretreated. The majority of these patients are [around age] 70, and they’re already prone to infections because they have diabetes or uncontrolled hypertension or because they’ve been on dexamethasone for a long time.
To reduce the risk of infections, acyclovir is recommended to reduce the risk of shingles reactivation. In some cases we’re seeing reactivation of CMV [cytomegalovirus]. In rare cases we’re seeing EBV [Epstein-Barr virus]. We’ve seen PCP [pneumocystis pneumonia] in patients receiving treatment with the BCMA bispecific agent, which we’re not used to seeing in myeloma care. We’re used to seeing this in allogeneic transplants, but not in this scenario. The introduction of Bactrim prophylaxis is also in discussion, and it’s another agent that needs to be considered in addition to acyclovir. This is another cost to keep in mind, especially if a patient has an insurance co-pay for oral medication or a deductible for oral medication.
Transcript edited for clarity.
