Comparison of Efficacy in Patients with Metastatic Melanoma Treated with Ipilimumab and Nivolumab Who Did or Did Not Discontinue Treatment Due to Immune-Related Adverse Events: A Real-World Data Study

Abstract

Immune-related adverse events (irAEs) are very prevalent when treating patients with ipilimumab and nivolumab in combination, and 30–40% of patients discontinue the treatment for this reason. It is of high clinical relevance to investigate the consequences of discontinuing the treatment early since combination therapy with ipilimumab and nivolumab is the first line of treatment for many patients with metastatic melanoma. In this follow-up study, with real-world data from the nationwide DAMMED database, we investigated whether there was a difference in progression-free survival (PFS) and overall survival (OS) for patients who discontinued or did not discontinue treatment within the first four doses of treatment due to irAEs. In total, 448 patients were treated with ipilimumab and nivolumab. Of these, 133 patients discontinued due to irAEs in the induction phase. Using the Cox proportional hazards model, there was no significant difference in PFS when comparing the group that discontinued with the group that did not discontinue. The group that discontinued had a significantly longer OS than the group that received the full length of treatment. Therefore, we conclude that there is no significant negative impact on efficacy for patients who discontinue due to irAEs in the induction phase of combination immunotherapy for metastatic melanoma.

Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial

“…These results are consistent with previous reports in patients who discontinued dual nivolumab plus ipilimumab due to TRAEs, including data from CheckMate 227 and from patients with advanced sarcomatoid renal cell carcinoma in CheckMate 214. 8 37 Similar findings have been reported recently from a real-world data analysis in melanoma 38 and NSCLC, 39 40 which showed that patients may experience a durable response even after discontinuing immunotherapy for any reason or due to adverse events.…”

Sentinel lymph node biopsy is unreliable in predicting melanoma mortality for both younger and older patients

“…However, up to or over 15 patients can be expected to suffer grade 3 to 4 adverse events 31–33 . If ipilimumab is combined with PD‐1 therapy, up to 50 patients could be expected to discontinue therapy because of adverse events 34,35 . The impact of immune related adverse events associated with PD‐1 therapy has been identified, including the prolongation of these events following drug cessation 36 .…”

“…[31][32][33] If ipilimumab is combined with PD-1 therapy, up to 50 patients could be expected to discontinue therapy because of adverse events. 34,35 The impact of immune related adverse events associated with PD-1 therapy has been identified, including the prolongation of these events following drug cessation. 36 Thus, the potential risk of patient harm may outweigh the benefit for these young very low-risk patients.…”