D1.369 - Immediate hypersensitivity to dostarlimab successfully managed with desensitization

Dostarlimab is an anti–PD-1 monoclonal antibody approved in combination with carboplatin and paclitaxel for the treatment of patients with advanced or recurrent endometrial cancer. Although infusion-related reactions have been reported, an underlying IgE-mediated mechanism has not been described to date.

A 67-year-old woman with a medical history of hypertension, type 2 diabetes mellitus, dyslipidemia, and endometrioid endometrial cancer was referred to our Allergy Unit after experiencing an adverse reaction during oncologic treatment administration. She attended the Oncology Day Unit for the first cycle of dostarlimab, paclitaxel, and carboplatin, with no previous exposure to oncologic treatments. After administration of 500 mg of dostarlimab and 10 minutes following completion of the paclitaxel infusion (237.6 mg), the patient developed intense erythema involving the face, décolletage, and upper limbs. Symptoms resolved after treatment, and carboplatin was not administered on that occasion.

An allergy workup was performed. Blood tests included measurement of serum tryptase levels during the acute reaction and at baseline. Skin testing with paclitaxel and dostarlimab was carried out, including testing of dostarlimab in healthy controls. Dostarlimab contains polysorbate 80 (PS80) as an excipient; however, the patient was already tolerating other PS80-containing medications in her ongoing treatment, so PS80 was not tested.

Serum tryptase levels measured during the reaction and at baseline were 4.86 µg/L and 5.10 µg/L, respectively. Skin testing was performed at least two weeks after the initial hypersensitivity reaction to minimize the risk of false-negative results. Skin tests and the drug provocation test with paclitaxel were negative. Intradermal skin testing with dostarlimab was performed using 1:100 and 1:10 dilutions, showing a positive result at a concentration of 50 mg/mL.

Dostarlimab was subsequently re-administered under allergist supervision with dexchlorpheniramine premedication, following a nine-step desensitization protocol using a single infusion bag (total dose 500 mg; volume 110 mL), starting at 1 mL/h with 15-minute dose escalations up to a final rate of 100 mL/h. The procedure was well tolerated, with no adverse events.

To our knowledge, this is the first reported case of suspected IgE-mediated hypersensitivity to dostarlimab, confirmed by positive skin testing, and successfully managed with an effective desensitization protocol that enabled safe continuation of treatment.