Hypersensitivity reactions to mAbs: 105 desensitizations in 23 patients, from evaluation to treatment
Received 13 July 2009; received in revised form 3 September 2009; accepted 8 September 2009. published online 12 November 2009.
Background
Rapid desensitization, a procedure for graded drug administration, allows for the safe readministration of a medication after certain types of hypersensitivity reactions (HSRs) and is indicated in cases in which there are no reasonable therapeutic alternatives. The use of rapid desensitization for HSRs to mAbs has not been validated.
Objective
We sought to describe our experience with rapid desensitization to mAbs, including rituximab, infliximab, and trastuzumab.
Methods
One hundred five rapid desensitizations were performed in 23 patients with a standardized 12-step, 6-hour protocol. Our approach to patient evaluation before desensitization is described. The severity, characteristics, and timing of both initial HSRs and HSRs during desensitization were determined by means of retrospective review of medical records. After a reaction during desensitization, patient-specific protocol modifications were made before each subsequent desensitization.
Results
104 of 105 desensitizations undertaken were successfully completed. We observed HSRs during 29% of desensitizations, including 27 mild reactions, 1 moderate reaction, and 2 severe reactions. Overall, reactions during desensitization were markedly less severe than initial HSRs, but reactions did recur in a minority of successive desensitizations.
Conclusions
Rapid desensitization is a promising method for the delivery of monoclonal therapeutics after an HSR, but the possibility of a reaction remains with each desensitization.
Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Mass
Reprint requests: Mariana Castells, MD, PhD, One Jimmy Fund Way, Smith Building, Room 626D, Boston, MA 02115.
The desensitization program at Dana Farber Cancer Institute and Brigham and Women's hospital is supported in part by Ovations for the Cure.
Disclosure of potential conflict of interest: P. J. Brennan received research support from the National Institutes of Health. T Rodriguez Bouza received research support from Real Colegio Complutense. F. I. Hsu received research support from Dyax. D. E. Sloane previously served on the speakers' bureau for Genentech and Novartis. M. C. Castells served as a consultant for Schering-Plough and ICON, received research support from Ovations for the Cure, and served as an expert witness on adverse drug reactions and desensitizations.
ABSTRACT