关键词: 免疫检查点抑制剂, 免疫疗法, 心肌炎, Janus激酶抑制剂

Abstract:

Background and purpose: Outcomes for cancer patients with steroid-resistant immune checkpoint inhibitor-associated myocarditis (srICIAM) are poor. Intensified immunosuppressive therapies, including tofacitinib, a novel Janus kinase (JAK) inhibitor, may have some therapeutic benefits. However, due to the lack of sufficient clinical data, the effectiveness of such treatments and their impact on cardiovascular outcomes remain unclear. This study aimed to investigate the therapeutic effect of tofacitinib on srICIAM. Methods: This retrospective case-control study included 36 malignant tumor patients who received immune checkpoint inhibitor treatment at Zhongshan Hospital affiliated to Fudan University from July 2019 to May 2022 and developed srICIAM. Patients receiving corticosteroids in combination with tofacitinib were assigned to the tofacitinib group (n=19), while those not treated with tofacitinib were allocated to the control group (n=17). The study compared clinical characteristics, laboratory findings, and imaging results between the two groups. Additionally, follow-up was conducted to monitor the incidence of cardiovascular endpoints in these patients. The research plan was approved by the Ethics Committee of Zhongshan Hospital Affiliated to Fudan University (Approval Number: B2021-275R). This study was conducted in accordance with the ethical guidelines of the Helsinki Declaration. Results: Compared to the control group, and with no significant difference in the cumulative dose and duration of corticosteroids (P<0.05), the tofacitinib group showed a shorter myocarditis recovery time (median recovery time: 86.5 days vs 126.5 days, P=0.021). The myocarditis-related mortality rate was significantly lower in the tofacitinib group than in the control group (5% vs 35%, P=0.025). Conclusion: Tofacitinib may reduce mortality and promote cardiac recovery in srICIAM patients without impeding the anti-tumor effect. It may become one of the potential treatment strategies in the future.

Key words: Immune checkpoint inhibitors, Immunotherapy, Myocarditis, Janus kinase inhibitor