D3.67 - Desensitization to Pertuzumab in a Patient with a Mixed Hipersensitivity Reaction

The increasing use of monoclonal antibodies has expanded the range of therapeutic targets but has also led to a rise in hypersensitivity reactions (HR), driven by different underlying mechanisms. Recognizing and appropriately managing these reactions is crucial, as alternative treatments with comparable efficacy and safety are often unavailable. In such cases, desensitization protocols can serve as a key therapeutic strategy.  Pertuzumab, a humanized monoclonal antibody, is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer in combination with other agents. We present a patient who developed an HR to pertuzumab, whose subsequent administration followed a 12-step desensitization protocol.

A 69-year-old woman diagnosed with invasive lobular breast carcinoma was scheduled for neoadjuvant treatment with carboplatin, docetaxel, trastuzumab and pertuzumab. During the 2nd cycle of treatment, shortly after initiating pertuzumab infusion, she developed facial/cervical flushing, sweating, dyspnea and desaturation (min SpO₂ 85%). The infusion was immediately stopped, and she was treated with hydrocortisone, clemastine and oxygen, with progressive symptom resolution. Acute tryptase level was not assessed. During this cycle and 3 subsequent ones, she tolerated individual infusions of the remaining drugs.

She was subsequently referred to an allergist and, 3 weeks after the reaction, skin testing was performed. A prick test (1.6 mg/mL) was negative, while intradermal testing (0.0016–0.16 mg/mL) was positive at 0.16 mg/mL. Given the necessity of an additional pertuzumab administration, a 12-step, 3-bag desensitization protocol was implemented, including a pre-medication regimen. Despite this, she developed urticaria, chest tightness and desaturation (min SpO₂ 90%) within minutes of the final step. The infusion was halted, and she was treated with hydrocortisone and clemastine. Once symptoms subsided, the infusion was resumed at a slower rate with continuous monitoring. However, shortly before completing the treatment, she experienced a recurrence of symptoms, now accompanied by fever (tympanic temperature 38.4°C). With symptom control achieved after clemastine and paracetamol administration, the full therapeutic dose was achieved. Acute tryptase value was within the normal range.

The patient has since undergone surgery and is now being considered for a new adjuvant treatment regimen.

This case highlights the challenges allergists face in diagnosing and managing HR to monoclonal antibodies. Proper classification into distinct phenotypes is essential for optimizing treatment; however, some patients may present with mixed reactions or experience phenotype shifts, complicating this process. Desensitization remains a valuable strategy for managing HR with diverse underlying mechanisms. Nevertheless, breakthrough reactions can still occur, requiring allergists to be prepared to adjust protocols accordingly.