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Aims Background: Temozolomide is an oral chemotherapy drug widely used in the treatment of glial tumours. This is generally well tolerated however, immediate and delayed hypersensitivity reactions have been described, necessitating treatment interruption that could significantly impact survival. Method Case description: We report a case of a 39-year-old young woman with WHO grade 2 IDH1mutant diffuse astrocytoma (MGMT promoter methylated) of the left temporal lobe. She had tumour resection in 2012 followed by radical radiotherapy. Afterwards, she had close surveillance with regular brain imaging. The tumour started to progress in early 2020. We agreed to commence on temozolomide to control tumour growth. She developed an itchy rash with easy bruising towards the end of the first cycle. It responded to a course of prednisolone. We proceeded with the second cycle and she developed a worsening rash on the third day. However she did not have signs or symptoms of anaphylaxis. This episode was again managed by a course of steroids and oral antibiotics. Since Temozolomide was the optimal treatment to control the disease progression at this stage, we agreed to persevere with temozolomide using a rapid desensitisation protocol. Results On the first day of third cycle, she was brought to the day chemotherapy unit and given prednisolone 30mg, fexofenadine 180mg and ondansetron 8mg, 30 minutes before the treatment. Our protocol was as follows; 5mg, 10mg, 20mg, 30mg, 50mg and 90mg of temozolomide at an interval of 30 minutes between the doses. She was advised to follow the same regime for the next four days of the third cycle. On days 6 -28, she has been advised to take fexofenadine 180mg once daily. Although there was a minor rash appeared on days 6/7, they subsided gradually. She tolerated the treatment without sinister symptoms or signs. We proceeded with the next 4 chemotherapy cycles adhering to the same protocol. The intensity of the rash gradually improved, and she became almost completely asymptomatic by the 7th cycle. It was also encouraging to see the radiological response of the tumour with the treatment. Conclusion Although the published literature is minimal, rapid desensitisation is shown to be a safe and effective method to counteract temozolomide hypersensitivity. In an era where there is still a paucity of systemic treatment options for primary brain tumours, adopting rapid desensitisation to induce tolerability to temozolomide, a drug which has shown to improve survival, would be a valuable addition in managing our patients. Further, our experience suggests that this protocol is safe, effective, and does not necessitate inpatient admission.