The ipi/nivo combo - responses in melanoma patients ~

As with most things in melanoma land, this is a topic I've covered before!  Here are lots of reports from recent years that cover response rates and outcomes for melanoma patients treated with the ipi/nivo combo:  Results of the ipi/nivo combo in melanoma patients

Now there is a report breaking down those responses:

Site-specific response patterns, pseudoprogression, and acquired resistance in patients with melanoma treated with ipilimumab combined with anti-PD-1 therapy.  Pires da Silva, Lo, Quek, et al. Cancer. 2019 Oct 4.  Patients with metastatic melanoma have variable responses to combination ipilimumab and nivolumab. The objectives of this study were to examine the patterns of response and survival in patients treated with combination ipilimumab and anti-PD-1 therapy (IPI + PD1) and to explore the nature of pseudoprogression and acquired resistance. Patients with metastatic melanoma who received treatment with first-line IPI + PD1 had all metastases ≥5 mm measured on computed tomography/magnetic resonance imaging studies. The lesional response rate (LRR) and the overall response rate (ORR) were determined according to Response Evaluation Criteria in Solid Tumors, version 1.1. In total, 140 patients who had 833 metastases were studied. The ORR and the overall complete response (CR) rate decreased as tumor burden or the number of metastases increased. Metastases that had a CR (49%) were smaller than metastases without a CR (median, 13 vs 17 mm). Soft-tissue and lung metastases had the highest LRR (79% and 77%, respectively), whereas liver metastases had the lowest (46%). In multivariate analysis, patients with lung metastases had superior ORR and progression-free survival, whereas those with liver metastases had inferior ORR, progression-free survival, and overall survival. Pseudoprogression occurred in one-third of patients who had progressive disease as their best response, with an overall survival that was comparable to that of patients without disease progression. Acquired resistance occurred in 12% of responders after a median of 9.6 months, with an overall survival rate of 83% at 1 year from progression. Metastases in different anatomical locations display distinct response patterns and also are associated with overall response and survival with combination immunotherapy. Specific sites of disease may hold unique mechanisms of resistance and should allow for more personalized treatment.

This report looked at 140 patients as well as their combined 833 lesions.  Smaller tumors responded better than big ones.  Lung and soft tissue tumors responded better than tumors in the liver, leading to greater overall response rates, progression free survival, as well as overall survival in patients with lung mets versus those with liver tumors.  Pseudoprogression is real, but only occurs in 1/3 of patients with progressive disease.  And finally, about 12% of responders stopped responding at about 9-10 months.

None of this is real news.  We know that patients with the lowest disease burden respond best to immuotherapy.  Sadly, we have also known for some time that folks with liver mets have a very tough go of it.  These reports go back to 2015:  Liver mets and response to immunotherapy  While researchers have long noted and worked to address resistance in targeted therapy, it is not often discussed in regard to immunotherapy.  But, this report does note that 12% of melanoma peeps on ipi/nivo may at first respond but stop doing so some months later.

We've come a long way, but there is still much we need to learn to improve the plight of melanoma patients.  For what it's worth. - c