Toxicities in immunotherapy: Can they predict response?

Abstract

e14534 Background: Checkpoint inhibitors have been shown to improve survival outcomes in patients with metastatic malignant melanoma. However, the use of these agents is associated with a unique spectrum of immune related toxicities. Despite this, durable responses on immunotherapy are still possible even in patients who experience grade 3 toxicities. Furthermore, trials to date have shown that steroids do not appear to affect survival. We present the long term data on real world toxicities and response rates for patients treated previously with Ipilimumab at a national academic cancer centre. Methods: All patients treated previously with Ipilimumab at our centre were identified from pharmacy records. We performed a retrospective paper and electronic review and extracted relevant demographic data (age, sex) and clinical data (number of cycles, incidence and grade of immune related adverse events, interruption/cessation of therapy, need for immunosuppression, initial response to treatment and time to progression). Results: 33 patients with metastatic malignant melanoma were treated with Ipilimumab at our centre from 2011 to 2016. The incidence of G1, G2 and G3 toxicities was 33% (n = 11), 6% (n = 2) and 29% (n = 9), respectively. 23% (n = 7) of patients required steroids and 6% (n = 2) required TNF-a inhibitors. Treatment was stopped in 23% of patients due to Grade 3 toxicites. Of the grade 3 toxicities, colitis was the most common (46%, n = 6). In addition, rare toxicities were idenfied including orbital myositis (1 patient) and myelitis (1 patient). The response rate in the patient subset that required steroids was 42% vs. 15% in those that did not. The median duration of response in those that required and did not require steroids was 8 and 7 months respectively. Conclusions: Higher response rates and a longer median duration of response was seen in patients with grade 3 toxicities requiring steroids. The incidence of toxicities may reflect increased immunotherapy activity, thus leading to superior response rates. Further studies are needed to assess if earlier use of steroids to mitigate toxicities and the possibility of