Sequential immunotherapy in melanoma: is it a realistic alternative to dual immunotherapy?

Abstract

The treatment of metastatic melanoma has been revolutionised with the emergence of checkpoint inhibitors. The combination of Ipilimumab and Nivolumab offers the longest overall survival but is considerably more toxic than single-agent therapy. For patients who received single-agent immunotherapy it is unclear whether secondline immunotherapy is efficacious or tolerable. This study looked at outcomes for patients treated with sequential immunotherapy and compared them to patients who received dual immunotherapy. Fifty-eight patients received both Ipilimumab and an anti-PD-1 agent during the 5-year period, twenty-seven received dual immunotherapy, twenty received first-line Ipilimumab and eleven received an anti-PD-1 agent first line. The median overall survival (OS) was 24.8 months. The 5 year survival was greatest in patients treated with dual immunotherapy (42%) compared to first-line anti-PD-1 (33.3%) and first-line Ipilimumab (0%). As second-line treatments, anti-PD-1 agents had a median OS of 16.5 months compared to Ipilimumab at 3.4 months. 77.8% of patients had grade 3/4 toxicity with dual immunotherapy compared to 10% of patients treated with first-line Ipilimumab and 0% with anti-PD-1 agents. In the second line, 72.7% of patients treated with Ipilimumab experienced grade 3/4 toxicity, compared to 20% of patients treated with second-line anti-PD-1 agents. This study suggests Ipilimumab is not efficacious in patients who progress after anti-PD-1 agents, and this sequential approach does not avoid toxicity. The emergence of new checkpoint inhibitors will hopefully provide more efficacious treatment options for patients unable to tolerate Ipilimumab. Melanoma Res 31: 366

Remodeling the tumor-immune microenvironment by anti-CTLA4 blockade enhanced subsequent anti-PD-1 efficacy in advanced nasopharyngeal carcinoma

“…This temporal characteristic suggests that sequential therapy, administering anti-CTLA4 followed by anti-PD-1 treatment, could potentially synergize the effects of these two drugs, making the toxicity more manageable. Previous trials in melanoma support this, showing that sequential therapy was associated with better survival outcomes than monotherapy and dual immunotherapy 13 . Therefore, sequential therapy may offer a more efficacious and safer alternative for NPC patients.…”

“…To address this limitation, as displayed by previously trials in melanoma, sequential administration of anti-CTLA4 followed by anti-PD-1 treatment might synergize the effect of these two drugs and make the potential toxicity more controllable 12 , 13 . In a cohort of 271 patients with melanoma, treatment with sequential anti-CTLA-4 and anti-PD-1 was associated with a better survival outcome than monotherapy with anti-PD-1 or anti-CTLA-4, anti-PD-1 followed by anti-CTLA-4 or dual immunotherapy 12 .…”

Durable Responses in Patients With Advanced Cholangiocarcinoma on Sequential Dual-agent Immunotherapy After Progressing on Single-agent Immunotherapy

“…In another trial, it was shown that ipilimumab was not effective in patients with melanoma, which progressed after anti-PD-1 agents. 12 A group of researchers from Hong Kong published results of sequential immunotherapy in HCC. Patients who progressed on either nivolumab or pembrolizumab were switched to either ipilimumab/pembrolizumab or ipilimumab/nivolumab on the basis of a prior anti-PD-1 agent.…”

“…The switch of checkpoint inhibitor in this trial was scheduled regardless of response. In another trial, it was shown that ipilimumab was not effective in patients with melanoma, which progressed after anti-PD-1 agents 12…”