Biologics in the treatment of immune-related adverse events: A systematic review.

Abstract

e14650 Background: Immune-related adverse events (irAEs) are frequently reported among oncology patients undergoing immune-checkpoint inhibitor (ICI) therapy. Biologic agents have emerged as a promising irAE treatment, but the extent to which biologics are used in the management of ICI-induced irAEs, its efficacy and safety, remain unclear. Methods: Empirical, peer-reviewed studies from PubMed, EMBASE, and Cochrane were searched. Studies were included if they included adult oncology patients undergoing ICI (anti-PD(L)-1, anti-CTLA-4, or combination) therapy who developed irAEs, and were treated with biologics. Studies were excluded if patients were undergoing clinical trials. Results: 116 studies were included. The most frequently reported irAEs were colitis (32.8%), cutaneous irAEs (cirAEs) (27.6%), and pneumonitis (12.9%). 87.0% of studies reported complete or partial resolution of irAEs. Infliximab was the most prescribed (48.3%) biologic for irAEs, particularly colitis, though it had the lowest response rates (32.1%). Highest complete response rates were reported in tofacitinib and secukinumab (100% and 75.0%, respectively). Anti-IL-17 and anti-IL-23A agents showed the highest rates of complete resolution of cirAEs. Dupilumab was also associated with high response rates, though most studies reported subsequent cancer progression in treated patients. Conclusions: Biologics in the treatment of irAEs appear efficacious and well tolerated, particularly for steroid-refractory irAEs. Although most studies report on infliximab, other biologics may be more effective. Biologics had minimal toxicities, but close follow-up is needed for more vulnerable populations. More research reporting long-term outcomes following rechallenge of ICI is needed. Biologics and their efficacy in the top three most frequent irAEs: colitis, cirAEs, and pneumonitis. IrAE Biologic Response Colitis Infliximab CR [20,31,34,50,100,103,111,120,125] PR [19-21,28,30,34,39,66,71,96,105,108, 126,132] N/R [39,66,126] Worsened [40] Vedolizumab CR [24,50,105,116,129,131,133] PR [64,109,129,131] Tocilizumab CR [22] PR [22] Ustekinumab CR [83] PR [117] N/R [117] Tofacitinib CR [119,125] cirAEs Secukinumab CR [21,86] PR [72] Omalizumab CR [13,49,57] PR [13] Rituximab CR [13,35,45,48,57] PR [13,122] Risankizumab PR [11,51,73] Dupilumab CR [13,45,58,59,81] PR [11,13,27,36,45,56,122] Apremilast CR [69] PR [29,60] Ixekizumab CR [94] PR [78] Ruxolitnib CR [76] Upadacitinib PR [80] Ustekinumab CR [52] PR [11,52,122] Adalimumab PR [37] Guselkumab PR [122] Tocilizumab CR [41] Pneumonitis Infliximab CR [44,129] PR [28,44,63,68,74,104,121,128,129] N/R [38,129] Worsened [44,62,127,129] Tocilizumab NR [121] irAE, immune-related adverse event; CR, complete resolution; PR, partial resolution; N/R; no response, NR, not reported.