Rituximab Desensitization in Pediatric Patients: Results of a Case Series

Abstract

Rituximab is a monoclonal antibody (mAb) primarily used to treat oncologic and autoinflammatory conditions. Although hypersensitivity reactions (HSRs) and desensitization protocols to mAbs have been well described in adults, the experience in the pediatric population is very limited. We sought to determine the safety and efficacy of desensitization to rituximab in the pediatric population at our institution. We retrospectively reviewed the experience with HSRs and desensitization to rituximab during a 5-year period in our tertiary care pediatric center, including reaction evaluation, premedication regimens, and desensitization procedures and protocols. A total of 17 desensitizations to rituximab were performed in three patients. A 14-year-old patient underwent successful desensitization to rituximab using a published adult protocol without incident. Two younger patients (ages 7 years and 23 months) experienced significant reactions during initial desensitization attempts. Therefore, we designed a modified desensitization protocol to rituximab, with particular attention to the rate of infusion as mg/kg/h. This new patient weight-based protocol was successfully used in a total of 13 desensitizations in these two patients. Desensitization to rituximab was a safe and effective procedure in our pediatric population. We present a new patient weight-based desensitization protocol for pediatric patients who develop HSRs to rituximab, with particular usefulness for younger pediatric patients and potential utility in pediatric patients with HSRs to other mAbs.

Hypersensitivity Reactions to Monoclonal Antibodies in Children

“…RDD protocols to mAbs have been well defined in adults but there is limited experience in the pediatric population. Successful desensitization protocols in children has been reported for rituximab [125,134,135], infliximab [103,136] and tocilizumab [135]. Desensitization to infliximab had already successfully performed in 2001 for a 10-year-old boy with severe ulcerative colitis who had experienced an immediate severe anaphylactic/anaphylactoid reaction after repeated infusions of this drug.…”

“…Dilley et al [134] present three cases of pediatric patients. A 14-year-old boy with X-linked lymphoproliferative disease had a systemic reaction to rituximab for treatment of granulomatous lymphocytic interstitial lung disease.…”

“…This protocol involved 14-steps using three solutions with different concentrations. The initial dose was 1:50,000 of the total dose and the increment of the infusion rate was approximately 0.5 mg/kg/hour, with the final infusion rate not exceeding 2 mg/kg/hour [125], similar to the protocol proposed by Dilley et al [134]. RDD is a costly and time-consuming procedure, possibly associated with serious reactions.…”

Desensitization to biological agents used in rheumatology

“…A recent publication proved that desensitization is a safe and cost-effective procedure [3]. Desensitization to drugs used in rheumatology such as TNF blockers , rituximab [8,15,18,19,[30][31][32][33][34][35][36][37][38][39][40][41][42], tocilizumab [43][44][45][46][47][48], IL-17 blockers (ixekizumab) [49] and anti-IL-1 (anakinra) [50][51][52][53] has been described. Most of the described procedures were performed in patients with rheumatoid arthritis [8,32] but desensitization in patients with lupus or spondyloarthropathies [24], adult-onset Still disease [43], IgG4-related disease [40] and autoinflammatory disorders [51][52][53] has also been performed with success.…”

Rituximab desensitization in pediatric acute lymphoblastic leukemia with severe anaphylaxis

“…Desensitization should be considered when treatment options are limited for continued use of these drugs in patients with a history of HSRs. 6…”