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Slowed Infusions Cut Hypersensitivity Reactions in Rituximab Desensitization

April 5, 2012

A slowed, rate-controlled infusion of rituximab during a desensitization protocol significantly reduced the number of hypersensitivity reactions compared with faster, standard-rate desensitization infusions.

“The safety of rituximab desensitization was improved using rate-controlled protocols,” said Dr. Caroline L. Sokol, who discussed a review of 16 patients who underwent 103 desensitizations at a single U.S. center. The findings prompted her division to switch to rate-controlled infusions for all rituximab desensitization protocols, said Dr. Sokol of the division of allergy and immunology at Massachusetts General Hospital, Boston (J. Allergy Clin. Immunol. 2012;129[suppl.]:AB371).

Hypersensitivity reactions to rituximab primarily occur among patients who receive the drug to treat cancer. Patients who receive rituximab for other indications, such as rheumatoid diseases, rarely have hypersensitivity reactions. The explanation for this difference isn’t clear, Dr. Sokol said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In the series she reviewed, 15 patients received rituximab for cancer and one patient received it to treat multiple sclerosis.

She and her associates also plan to assess the safety of rate-controlled infusions for desensitization to other drugs, including other types of monoclonal antibodies and platinum-containing cancer chemotherapy drugs.

They compared the safety of standard and rate-controlled infusions with rituximab because some cancer patients who receive the drug experience hypersensitivity reactions that are not controllable with antihistamine or steroid pretreatment. These patients must therefore undergo desensitization, a step that usually needs to be repeated every time they start a new course of the drug.

To compare the two infusion protocols, the researchers reviewed the Massachusetts General experience using the rate-control method during 2006-2008 as well as in 2011-2012. Those results were compared against the outcomes using a standard-infusion protocol during 2008-2011.

Dr. Caroline L. Sokol


Among the 103 total rituximab desensitization procedures done on 16 patients during 2006-2012, 75 protocols used the rate-controlled method with a fixed infusion rate that delivered no more than 200 mg/hr of rituximab and 28 used a standard protocol that delivered a fixed fluid volume with varying rituximab concentrations that finished at 320 mg/hr. Most patients underwent desensitization with each of the two methods at some point during the 6 years included in the review. The average age of the 16 patients was 51 years, and they were equally split between men and women.

The 75 rate-controlled desensitizations resulted in 13 hypersensitivity reactions (17%), including 6 mild reactions, 5 moderate, and 2 severe. The 28 standard desensitizations produced eight reactions (29%), a statistically significant difference compared with the rate-control incidence, and included two mild, five moderate, and one severe reaction, Dr. Sokol reported.

The reaction rate was highest in three patients who converted from rituximab skin-test negative to skin-test positive during the course of their 28 desensitization protocols. Hypersensitivity reactions occurred in nine of these 28 protocols (32%). In contrast, the reaction rate was 19% in patients who remained skin-test negative throughout their desensitizations. Among those who remained consistently skin-test positive, the reaction rate was 16%, she said.

Dr. Sokol said that she had no disclosures.



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