Monoclonal antibody cancer treatments such as rituximab have a high risk for hypersensitivity reactions (HSR) from cytokine release syndrome. The symptoms, which can range from mild to life threatening, result from tumor antigen-expressing cells releasing cytokines (e.g., tumor necrosis factor, interleukin, interferon) into the blood as they are destroyed. Symptoms include fever, chills, rigors, rash, headache, hypotension, shortness of breath, bronchospasm, nausea, vomiting, and abdominal pain.

In their article in the August 2018 issue of the Clinical Journal of Oncology Nursing, Laudati, Clark, Knezevic, Zhang, and Barton-Burke shared findings from their study comparing the incidence of HSR when IV lines for first infusions of rituximab were primed with the drug versus a diluent.  

Hypersensitivity Reactions With Rituximab

According to Laudati et al., the manufacturer reported a 77% incidence of HSR with the initial dose of rituximab. “The highest percentage of targeted cells are destroyed with this first dose, resulting in a decreased tumor burden and less cytokine release with subsequent infusions,” the authors explained.

When HSR occur, they can prolong infusion time; require administration of rescue medication; increase stress and anxiety for patients and caregivers, as well as healthcare professionals; and disrupt nursing workflow. Preventing HSR is key for optimal experience and outcomes.

Routine premedication with antihistamines and antipiretics and titrating infusion are standard prevention strategies. A slow, titrated infusion allows patients to have incremental exposure to the drug and cytokines to release more gradually. Laudati et al. cited the drug’s original studies, which started infusions at 50 mg per hour and titrated to a maximum of 400 mg per hour. However, they noted that those studies did not investigate whether priming the lines with diluent (normal saline or dextrose 5%) or the drug itself had an effect on the incidence of HSR.

Priming With Diluent Versus Drug

 When priming IV lines with diluent, patients receive diluent instead of the drug during early titration phases. Using a highly reactive drug such as rituximab to prime the IV line, however, allows for slow exposure to the drug, as recommended in the literature, Laudati et al. explained.

Their institution changed practices in mid-2016 from using diluent (normal saline) to using rituximab. Laudati et al. conducted a descriptive study using a retrospective chart review to compare the incidence of HSR before and after the practice change took place. They reviewed 200 patient charts: 100 in the diluent arm and 100 in the drug arm.

Overall HSR incidence across both arms was 27% (n = 54), which Laudati et al. (2018) noted was lower than the manufacturer’s reported 77%. But when broken down by priming practice, incidence was significantly higher in the diluent-primed arm than the drug-primed arm (35% versus 19%, respectively; p = 0.01). Overall median time to HSR was 96 minutes for both arms, but patients in the diluent arm had a significantly longer median time to HSR than those in the drug arm (105 minutes versus 86 minutes, respectively; p = 0.008). Patients in the diluent arm also had a significantly higher median infusion rate than those in the drug arm (150 mg per hour versus 100 mg per hour; p = 0.01). Across both arms, all HSRs were classified as grade 2 according to the Common Terminology Criteria for Adverse Events.

The researchers also compared demographic data in the charts for all arms and found that women were nearly twice as likely to experience HSR than men (34% versus 21%, respectively),p=.04. Laudati et al. said that demographic data were not reported in the drug’s original studies.

Finally, they also looked at clinical characteristics across the charts and found that patients who received dexamethasone premedication were 59% less likely to experience HSR than those who did not (19% versus 37%, respectively; p = 0.005).

What This Means for Oncology Nurses

When the IV line was primed with rituximab, Laudati et al. found that patients were 66% less likely to experience HSR than when diluent was used. However, priming methods did not affect HSR severity.

Based on their study findings, the researchers recommended incorporating the priming of rituximab IV lines with the drug as a best practice to the already recommended use of standard premedication and slow titration of rituximab infusions to reduce HSR, adding that manufacturers could add it to the prescribing information to help standardize practice.

Additionally, because of the significantly lower HSR rate when dexamethasone premedication was administered, Laudati et al. suggested that “when weighed against patient tolerability and side effects, the use of this premedication seems to be a beneficial addition to the standard premedication regimen.”

Finally, the authors suggested that future research explore whether these findings could also be applied to reduce HSR from other titrated high-risk monoclonal antibody agents (e.g., daratumumab, obinutuzumab, ofatumumab, elotuzumab).

For more information and the opportunity to earn 0.5 contact hours of continuing nursing education (free for ONS members), refer to the full article by Laudati et al.

This monthly feature offers readers a concise recap of full-length articles published in the Clinical Journal of Oncology Nursing (CJON) or Oncology Nursing Forum. This edition summarizes “Hypersensitivity Reactions: Priming Practice Change to Reduce Incidence in First-Dose Rituximab Treatment,” by Carissa Laudati, BSN, RN, OCN®, Caroline Clark, BSN, RN, OCN®, Andrea Knezevic, MS, Zhigang Zhang, PhD, and Margaret Barton-Burke, PhD, RN, FAAN, which was published in the August 2018 issue of CJON. Questions regarding the information presented in this article should be directed to the CJON editor at Photocopying of this article for educational purposes and group discussion is permitted.