Successful Desensitization to Brentuximab Vedotin After Hypersensitivity Reaction
June 2014 | Volume 13 | Issue 6 | Case Reports | 749 | Copyright © June 2014
Sara K. Story MD,a Andrej A. Petrov MD,b and Larisa J. Geskin MD FAADa
aUniversity of Pittsburgh, Department of Dermatology, Pittsburgh, PA
bUniversity of Pittsburgh, Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Pittsburgh, PA
Monoclonal antibodies (mAb) have become the standard of care for numerous diseases.
However, side effects including infusion and hypersensitivity reactions experienced by patients
continue to be a limiting factor in their use. In the therapy of cancer, treatment choices are
frequently limited and minimizing side effects of a life-saving or life-prolonging therapy becomes
of the utmost importance. We report the successful use of a rapid desensitization protocol in a
patient with NHL, treated with a novel antibody-drug conjugate, chimeric monoclonal antibody linked
to the antimitotic agent monomethyl auristatin E (MMAE) Brentuximab vedotin, who had previously
developed a hypersensitivity reaction. J Drugs Dermatol.
Monoclonal antibodies (mAb) are a growing area in the therapeutic
armamentarium of numerous conditions including various cancers,
autoimmune diseases, psoriasis, transplant rejection and cardiovascular diseases
among others1. They allow for targeting of specific proteins, cell markers and
cell receptors with the aim of maximizing treatment efficacy while minimizing
adverse effects.2 The use of mAb can be limited by hypersensitivity reactions
that occur during or shorty after infusion. These reactions can range from fever
or rigors to systemic anaphylaxis. In cancer patients, where therapeutic choices
are limited, such reactions represent significant setback and necessitate the use
of less optimal and more toxic alternatives, hindering successful therapy.
Desensitization protocols have been developed and successfully implemented
for patients that have previously had reactions to several mAb.3 Though desensitization
does not completely eliminate the risks associated with re-administration of medications
it does open the option to patients who otherwise may be treated with less optimal or
more harmful medications. Desentization protocols differ among various antibodies; hence it is important to gather
new information for successful management of these rare, but significant reactions.
Brentuximab vedotin is a novel antibody-drug conjugate approved to treat
anaplastic large cell lymphoma (ALCL) after failure of at least one prior
multi-agent chemotherapy regimen and Hodgkins lymphoma. It is a chimeric
monoclonal antibody which targets the cell-membrane protein CD30, linked
to an antimitotic agent monomethyl auristatin E (MMAE).4 Two cases of
anaphylaxis were reported in phase 1 trials. In phase 2 trials 19 patients (12%),
reported a Grade 1 or 2 infusion-related reaction.5
Here we report the successful desensitization of a patient with folliculotropic mycosis fungoides (F-MF)
after a hypersensitivity reaction to brentuximab vedotin (BV).
CB is a 57-year-old Caucasian female with a 3-year history of progressive
CD30+ F-MF who had failed adequate courses of interferon-α2β, oral bexarotene (>300mg/m2) and
romidepsin (14mg/m2). She enrolled in a clinical trial for brentuximab vedotin receiving 1.8mg/m2 over 30 minutes every 21 days. No pre-medications were permitted in the trial. Her first infusion was
tolerated well; she reported fatigue, mild muscle aches, intermittent tingling of her fingers and toes and
loose bowel movements. During her second infusion she began to have hives on her forearms approximately
half way through the infusion. The infusion was stopped and she received 50mg of diphenhydramine
and 125mg of methylprednisolone with resolution of all symptoms.
The infusion was restarted and completed without