D1.376 - Successful Desensitization with Temozolomide in a Patient with a Hypersensitivity Reaction to Temozolomide

Introduction

Temozolomide (TMZ) is an alkylating agent widely used in the treatment of glioblastoma and refractory anaplastic astrocytoma. Hypersensitivity reactions to TMZ are rare, with a limited number of early and late type reactions reported in the literature. Here, we present a case of generalized urticaria induced by temozolomide that was successfully managed using a rapid desensitization protocol.

Case

A 46-year-old woman was referred to our clinic for evaluation of a suspected allergic reaction following TMZ. She was diagnosed with glioblastoma in April 2024 and received concomitant radiotherapy and with daily TMZ 125 mg/day (75 mg/m²) for six weeks. Maintenance therapy was initiated in June 2024, consisting of TMZ administered for 5 consecutive days per month, planned for six cycles at 340 mg/day (150–200 mg/m²); the dose was subsequently reduced to 300 mg/day due to fatigue and thrombocytopenia.

She tolerated the July cycle without complications. During the August cycle, she experienced mild pruritus on days 3 and 4 but completed treatment. In September, on day 5 of the fourth cycle, she developed generalized urticaria within four hours after TMZ ingestion and was treated in the emergency department with intravenous dexamethasone and pheniramine. At presentation to our clinic, the lesions had resolved; however, patient-provided photographs were consistent with urticaria (Figure 1). Given the timing and clinical features, an immediate-type hypersensitivity reaction to TMZ was considered.

As no effective alternative treatment was available, continuation of TMZ was deemed necessary at a dose of 240 mg/day. Following premedication with cetirizine and methylprednisolone, a 12-step rapid desensitization protocol (Table 1 and 2) was performed successfully. The protocol began at approximately 1/10.000 (0.025mg) of the target dose, with scheduled dose escalation followed by oral administration to the full target dose without adverse reactions. The patient successfully completed desensitization with 240 mg TMZ on two separate occasions.

Conclusion

Hypersensitivity reactions to TMZ are uncommon. In cases where alternative therapies are unavailable and continuation of TMZ is critical, rapid desensitization represents a safe and effective strategy that allows patients to continue essential treatment.