Incidence of immune-related adverse events and its association with treatment outcomes: the MD Anderson Cancer Center experience

Abstract

Background Immunotherapy is emerging as the cornerstone for treatment of patients with advanced cancer, but significant toxicity (immune-related adverse events [irAEs]) associated with unbridled T cell activity remains a concern. Patients and methods A retrospective review of the electronic medical records of 290 patients with advanced cancer treated on an immunotherapy-based clinical trial in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center between February 2010 and September 2015 was performed. Clinical and laboratory parameters were collected to determine the incidence of irAEs, risk factors, and their association with treatment outcomes. Results Ninety eight of 290 patients (34%) experienced any grade irAEs. Among the 15 (5.2%) patients with grade ≥ 3 irAEs, the most common irAEs were dermatitis and enterocolitis. Although 80% of the patients with grade ≥ 3 irAEs required systemic corticosteroids, all the 15 patients recovered from the irAEs. On re-challenge, 4 of the 5 patients who had received systemic corticosteroids for irAE continued to respond. There were no irAE-related deaths. Importantly, patients with grade ≥ 3 irAEs had improved overall response rate (25 vs. 6%; p = 0.039) and longer median time to progression (30 weeks vs. 10 weeks; p = 0.0040) when compared to those without grade ≥ 3 irAEs. Conclusion Incidence of irAEs with immunotherapeutic agents indicates an active immune status, suggestive of potential clinical benefit to the patient. Further validation of this association in a large prospective study is warranted.

Cancer outcomes in patients requiring immunosuppression in addition to corticosteroids for immune‐related adverse events after immune checkpoint inhibitor therapy

“…Although better outcomes have been suggested for patients who experienced irAEs by some series, others have found no correlation . Where patients required immunosuppression in these studies, almost all were treated with corticosteroids only.…”

“…Although better outcomes have been suggested for patients who experienced irAEs by some series, [9][10][11][12]21 4 With regard to understanding the role of TNF to both immunemediated anticancer activity and irAEs, preclinical data are conflicting.…”

“…There has been significant interest in the relationship between irAEs and cancer outcomes. Several case series have demonstrated ongoing clinical benefit, and perhaps even a heightened response, from checkpoint inhibitor therapy despite cessation for irAEs . The largest of these, a case series from the Memorial Sloan Kettering Cancer Centre, reported on the outcomes of 103 patients who received corticosteroids or additional immunosuppressive medications to treat irAEs.…”

“…Several case series have demonstrated ongoing clinical benefit, and perhaps even a heightened response, from checkpoint inhibitor therapy despite cessation for irAEs. [7][8][9][10][11][12] The largest of these, a case series from the Memorial Sloan Kettering Cancer Centre, reported on the outcomes of 103 patients who received corticosteroids or additional immunosuppressive medications to treat irAEs. In their series, 31 steroid-refractory patients received TNF inhibitors or mycophenolate for immune-related adverse effects secondary to ipilimumab, without a discernible impact on time to treatment failure (TTF) or overall survival (OS).…”

FDG PET/CT for assessing tumour response to immunotherapy

“…The irAE pattern is different across immune checkpoint inhibitor classes and could be driven by the different patterns of immune cell activation that can occur with different classes of immune therapy [9]. The rapid identification of these irAEs and the initiation of systemic immunosuppression, for example with corticoids [10, 11], can improve patient outcomes.…”