Early Intervention for CRS Is Key for Patients With Multiple Myeloma Receiving Bispecific Antibodies

By monitoring patients with multiple myeloma who are undergoing treatment with teclistamab-cqyv (Tecvayli) for signs of cytokine release syndrome (CRS), such as fever, nurses can rule out infections and administer supportive care measures.¹ The bispecific antibody was granted accelerated approval for patients with multiple myeloma who have already undergone 4 prior lines of therapy, in October 2022.²

At the 48th Annual Oncology Nursing Society (ONS) Congress, Donna Catamero, ANP-BC, OCN, CCRC, presented safety data from the pivotal phase 1/2 MajesTEC-1 study (NCT03145181/NCT04557098), which supported the accelerated approval.^1,2 The safety data that Catamero presented demonstrated that 72.1% (n = 119) of patients receiving teclistamab on the trial (n = 165) developed CRS. Among these patients, most cases were either grade 1 (50.3%) or grade 2 (21.2%) events; 1 patient experienced a grade 3 event in an infection setting. Supportive care measures included tocilizumab (Actemra), intravenous fluids, low-flow oxygen, and steroids, among others. There were no recurrent cases of CRS reported, which Catamero attributed to early intervention.¹

“[In] our real-world experience managing CRS [that occurs] with bispecifics, we intervene early,” she told Oncology Nursing News®. “All our institutions use tocilizumab with grade 1 CRS, and we found that, by intervening early on, we did not have recurrence of CRS. Our CRS experience was mainly limited to grade 1 and 2.”

In an interview following her presentation, Catamero, a nurse practitioner and the associate director of Myeloma Research at Mount Sinai Hospital, detailed how nurses should intervene with supportive care measures after identifying CRS in patients.

Oncology Nursing News: What was the rationale behind this research?

Catamero: The MajesTEC-1 trial was a pivotal clinical trial that led to the FDA approval for teclistamab—a monoclonal antibody that targets the CD3 receptor on the T-cell and then the BCMA receptor on the myeloma cell. This being a novel drug, comes with novel adverse effects [AEs] and because it's redirecting T-cells in a similar fashion to chimeric antigen receptor T-cell [therapy], we see similar AEs. Our project was looking what are the best practice strategies to mitigate and manage CRS?

What were the different interventions used to identify and manage CRS?

The hallmark symptom for CRS is fever, so vital sign monitoring is key; in our various institutions, we were monitoring vital signs every hour to every 4 hours per institutional guidelines.

My colleagues and I are a global team, Europe was represented [as well as] the United States, and our institutions were very aggressive in managing CRS. We would intervene at grade 1 CRS, so [at a] 100.4 fever we would intervene with tocilizumab or other supportive care measures [which included] administering steroids, IV fluids, and vasopressors if needed. Usually, the first symptom is fever, but patients can also present with hypotension or hypoxia.

How important is it to rule out infections when assessing a patient and how often should physicians be consulted when monitoring patients?

Fever can mean anything. CRS with bispecifics is predictable, we know it is going to happen within that step-up dosing period, but you do not ever want to assume that it's an AE from the bispecific [because] you do not want to miss an infection. In conjunction, while managing CRS, we are doing that fever workup, so we are sending out cultures [because] we want to rule out the fever [and] make sure it's not an infection.

In our institutions, we have standard protocols for managing CRS. I can speak towards my institution where, at the first sign of CRS, we notify our physician colleagues, and we have a CRS attending available 24 hours. We have standing orders in place that if a patient meets the criteria, we are administering tocilizumab and steroids if needed—we have that interaction with the first symptoms of CRS.

What are the overall implications for oncology nurses practicing with teclistamab?

As nurses we are on the front line—we are at the bedside, we are monitoring patients for the symptoms of CRS. Educating our frontline providers, our nurses, on what the signs and symptoms are and how to best mitigate that [is important]. The step-up dosing rationale is to try to mitigate the occurrence of CRS and then once we see it, we want to intervene early to prevent recurrence or worsening rate of CRS.

Editor’s Note: This study was funded by Janssen Research & Development. The principal study author has received payment from GSK, BMS, and Janssen.

Reference

1. Catamero D, Blázquez Benito P, Shenoy S, Chastain K, and Kruyswijk S. Managing cytokine release syndrome in relapsed/refractory multiple myeloma: experience with teclistamab in the MajesTEC-1 study. Poster Presented at: 48th Annual Oncology Nursing Society Congress; April 26-30, 2023; San Antonio, Texas. Accessed May 4, 2023. https://ons.confex.com/ons/2023/meetingapp.cgi/Paper/13452
2. FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma. FDA. October 25, 2022. Accessed October 25, 2022. https://bit.ly/3f3HffB