Dermatologic Adverse Events in Acute Lymphocytic Leukemia Patients Treated with Bispecific T-Cell Engager Blinatumomab

Abstract

Blinatumomab is a novel FDA-approved bi-specific T-cell engager (BiTE) that significantly improves survival (vs standard chemotherapy) in adults with relapsed or refractory Philadelphia chromosome positive or negative B-cell precursor ALL (B-ALL) and is associated with high rates of clearing persistent measurable residual disease. Though the best known adverse effects associated with blinatumomab include cytokine release syndrome and neurologic toxicity, dermatologic adverse events (DAE) have also been reported in 16% of patients in clinical trials (FDA, 2018). In this study, we aimed to assess the incidence of DAEs in B-ALL patients treated with blinatumomab and characterize their associated clinical and histopathologic features. We conducted a retrospective analysis of B-ALL patients treated with blinatumomab monotherapy at Memorial Sloan Kettering Cancer Center from 1/1/2012 - 10/1/2021 (N=45). Seven patients experienced a total of nine DAEs (15.6%). Median number of blinatumomab cycles at time of DAE onset was one (range cycles 1-3). Median time to DAE onset following blinatumomab induction was 40 days (range 5-115 days). The most common DAEs were rashes (N=4); types included eczema, folliculitis, papular dermatitis, and panniculitis. Other DAEs (N=5) included new onset psoriasis, seborrheic dermatitis, acne, facial erythema, and nail dystrophy. All DAEs were grade 1, many DAEs did not require treatment, and no DAEs warranted interruption or discontinuation of blinatumomab. Four of the 7 patients with DAEs developed CRS at any point during blinatumomab therapy (ASTCT consensus grade 1, N=3; grade 2, N=1). Six of 7 patients with DAE achieved undetectable minimal residual disease (MRD) in the course of blinatumomab therapy or maintained MRD negativity. This is the most comprehensive study to report incidence and clinico-morphologic patterns of DAEs associated with blinatumomab monotherapy. Blinatumomab DAEs may be more common in patients who experience CRS; this finding may support that DAEs are the result of increased circulating cytokines secondary to effective immune activation by blinatumomab. DAEs are mild and we recommend that patients with severe rash during blinatumomab infusion are carefully evaluated for other etiologies of rash.