ML-12 Clinical impact and management of skin-related disorders during treatment of relapsed PCNSL by tirabrutinib

BACKGROUNDS: Tirabrutinib is a second-generation Bruton’s tyrosine kinase (BTK) inhibitor, approved by the Japanese Pharmaceutical and Medical Devices Agency (PMDA) for relapsed and refractory PCNSL in March 2020. Skin-related disorder (SRD)s are the most prevalent adverse events in tirabrutinib, which accounted for 54.5% in a phase I/II trial. While the use of tirabrutinib is increasingly considered in clinical practice, the prevalence and clinical impact of tirabrutinib-related SRDs in real-world practice remains unclear. METHODS: Relapsed PCNSL patients treated with tirabrutinib at the author’s institution were identified, and divided into those with SRDs (SRD group), and without SRDs (non-SRD group). Response rate and progression-free survival (PFS) were retrospectively analyzed and compared between the two groups. RESULTS: Eleven patients were identified (median age: 73 [range: 50–83], median KPS: 70 [range: 40–90]), which included six (54.5%) from the SRD group and five (45.5%) from the non-SRD group. Response rate was 100% in the SRD group and 60% in the non-SRD group. Median PFS was 2.8 months in the SRD group and 36.3 months in the non-SRD group, which yielded no significant difference (p=0.446). While antihistamine prophylaxis using fexofenadine was performed in seven patients, among them SRDs were observed in three (27.3%). SRDs lead to tirabrutinib interruption (for seven days or more) in two (18.2%), dose reduction in three (27.3%), and discontinuation in two (18.2%) patients. Four patients in whom tirabrutinib was interrupted or discontinued due to SRDs had shorter PFS, compared with the two patients from the SRD group in whom tirabrutinib was continued (median PFS: 2.3 and 29.6 months, respectively) (p=0.049). CONCLUSIONS: SRDs substantially lead to tirabrutinib interruption or discontinuation, which could result in early PD. Since fexofenadine prophylaxis seems ineffective for preventing SRDs, other antihistamines should be considered. Establishment of the optimal management of tirabrutinib-related SRDs is warranted.