433MO - Tofacitinib for the treatment of immune-related adverse events in cancer immunotherapy: A multi-center study

Background

Treatment strategy against immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents. Tofacitinib is a rapidly acting JAK-STAT inhibitor with proven efficacy in multiple autoimmune diseases. We aimed to evaluate the efficacy and safety of tofacitinib in the management of irAEs in cancer patients.

Methods

Cancer patients who received ICIs and treated with tofacitinib for the management of irAEs at 6 institutions were retrospectively included in this study. Demographic and clinical characteristics were obtained from electronic medical records. Longitudinal assessment of cardiac troponin T (cTnT) with clinical assessment was utilized to evaluate the benefit of tofacitinib treatment in patients with ICI myocarditis. Progression-free survival (PFS) and overall survival (OS) were also assessed.

Results

Fifty-three patients were included in this study. Median time from irAE onset to tofacitinib therapy was 17 (range, 2-186) days and median duration of tofacitinib treatment was 48.5 (range, 3-277) days. Enrolled patients were subdivided into 3 groups based on clinical severity and steroid responsiveness including 11 life-threatening cases, 30 steroid-resistant cases and 12 cases with steroid taper failure. Clinical remission rate in each group was 54.5%, 96.7%, and 100%, respectively (p<0.01). Tofacitinib was well-tolerated with 4 patients (7.5%) developing infectious events. From the ICI initiation, the overall median PFS was 5.6 (95% CI, 4.0-14.1) months, and the median OS was 16.1 (95% CI, 7.7-NR) months.

Conclusions

Tofacitinib showed promising clinical efficacy in patients experiencing irAEs, particularly in patients who failed to respond to steroid or experienced failure during steroid tapering. Moreover, and most importantly, tofacitinib exhibited a favorable safety profile in cancer patients developing irAEs in terms of both toxicity and anti-tumor activity. Future prospective studies are warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Zhongshan Hospital Affiliated to Fudan University; Chinese Society of Clinical Oncology.

Disclosure

All authors have declared no conflicts of interest.