Reviewed by Dr. Michael Burke
Picard M, et al. J Allergy Clin Immunol. 2015 Oct 19; 137(4):1154-1164
Anti-neoplastics are among the leading causes of fatal anaphylactic reactions in the United States with taxanes leading as the most frequent causative agent. Due to the dependency on taxane therapy, desensitization protocols have emerged for the delivery of chemotherapy in the setting of potentially fatal hypersensitivity reactions. The present study sought to risk stratify patients with history of taxane hypersensitivity by both reaction severity and skin-testing into either desensitization or challenge and to identify patients who may tolerate conventional protocols on re-exposure. The study population included 164 patients with documented hypersensitivity to paclitaxel (142) and docetaxel (22) with a wide variety of malignancies including ovarian, endometrial, breast, and prostate. Nearly all (106/110) patients with history of positive or equivocal skin test to taxane were submitted initially to desensitization with 23 progressing to intermediate dosage challenge and 13 tolerating all successive regimens and resuming full-dose infusion protocol. Of the patients with negative skin testing, 2 of 13 with history of severe reaction tolerated desensitization and were able to progress to challenge; the mixed cohort of prior moderate reactions and desensitization graduates yielded 22 patients of which 16 tolerated challenge; those 16 joined 5 skin test negative patients with history of mild reaction, all of which tolerated resumption of conventional protocol. The majority of patients followed tolerated re-exposure well with 89/138 without recurrent reaction and 31% with mild hypersensitivity or delayed reaction, most commonly flushing, and notably no instances of anaphylaxis. Patients with a history of atopic disease (31% of cohort) were more likely to suffer recurrent hypersensitivity reaction on re-exposure during desensitization or challenge as were those with history of gynecological malignancy.
Towards their primary endpoint the authors were successful in the resumption of full-dose infusions in 22% of the total cohort without a single episode of severe reaction; this latter point is notable as more aggressive protocols favoring rapid re-challenge have been reported with greater success rates (40-89%), however, with a 1-8% incidence of anaphylaxis on re-exposure and 2 documented cases of death in smaller cohorts. A significant proportion was not advanced from desensitization to challenge due to changes in the protocol implemented mid-study rather than inherent failure of the algorithm, ultimately affecting the reported success rate. While the present study provides data on likelihood to resume conventional infusions, in the absence of a concomitant comparison, little can be meaningfully claimed towards the superiority of the current risk-stratified algorithm over prior re-challenge approaches.