AI Summary
The content discusses the rising incidence of Merkel cell carcinoma (MCC) in the USA and the use of anti-programmed cell death (ligand) 1 (PD-(L)1) agents as the first-line treatment for advanced cases. However, approximately 50% of patients do not benefit from this treatment. In such cases, the addition of ipilimumab, an anti-cytotoxic T lymphocyte antigen-4, is sometimes used but its clinical benefit is debated. The review of one prospective study, three retrospective studies, and three case reports shows that the combination of anti-PD-(L)1 and ipilimumab resulted in an aggregate response rate of 32% with variability in response duration and immune-related adverse events. While adding ipilimumab may be beneficial for some patients with refractory MCC, there is still a significant unmet need for treatment options, highlighting the importance of further clinical trials in this area.
Merkel cell carcinoma (MCC) incidence has risen to approximately 3,000 cases annually in the USA. Although anti-programmed cell death (ligand) 1 (PD-(L)1) agents are now the first-line treatment for advanced MCC, approximately 50% of such patients do not persistently benefit. In PD-(L)1-refractory cases, ipilimumab (anti-cytotoxic T lymphocyte antigen-4) is often added; however, the extent of the clinical benefit of this combination is controversial. We identified one prospective study, three retrospective studies, and three case reports regarding this combination in refractory MCC. The aggregate response rate from retrospective studies was 32% (13 of 41 patients) with 4 complete responses (CR) and 9 partial responses (PR). In the prospective study, the response rate was very similar at 31% (8 of 26 patients; 4 CR, 4 PR). Response durability was highly variable (range 2 to >43 months), with patients achieving CR having greater durability. Immune-related adverse events (irAEs) were ≥grade III in 29% (retrospective cohort, N=41) and 36% (prospective cohort, N=50). While these aggregate data indicate adding ipilimumab should be considered in this setting, many patients with refractory MCC are ineligible due to comorbidities/irAEs, and approximately 70% will not benefit from this regimen. There is thus a significant unmet need in PD-(L)1-refractory MCC and clinical trials in this setting should be encouraged.