Prospective cohort study of JAK inhibitors for treatment of life-threatening and refractory irAEs secondary to immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but can induce immune-related adverse events (irAEs), which are sometimes severe, life-threatening, or refractory to corticosteroids. Dysregulation of the JAK-STAT pathway has been implicated in irAE pathogenesis. A prospective cohort study at the Jewish General Hospital (Montreal, Canada) evaluated JAK inhibitors (JAKi) for patients developing grade ≥ 3 or persistent grade 2 irAEs unresponsive to corticosteroids or life-threatening irAEs requiring urgent intervention. Among 29 patients, 5 were excluded due to death within 30 days of initiation of JAKi, leaving 24 evaluable patients. Indications for JAKi use included myocarditis, arthritis, colitis, hepatitis, encephalitis, pneumonitis, myasthenia gravis, and sicca syndrome. JAKi were employed as second-line therapy in 7 patients, third-line in 11, and fourth-line or later in 6. Clinical response, defined als irAE resolution to grade ≤ 1 while on ≤ 10 mg prednisone equivalent without relapse for ≥ 30 days, was observed in 17 patients (70.8%), with median time to resolution of 41 days. Response rates were highest for myocarditis (75%) and arthritis (100%). No opportunistic infections or JAKi-related hepatotoxicity occurred; thrombotic events were identified in three patients (10.3%). The authors conclude that these findings suggest that JAKi are a promising and well-tolerated option for managing corticosteroid-refractory or life-threatening irAEs.