Sorry you and your husband are dealing with all this, betsyl! Melanoma is never easy. Responses are variable – always. However, here is a report that addresses some of what you are asking:
Ultimately, this report indicates that starting ipi/nivo in patients who have been or are currently being treated with anti-PD-1 (Opdivo or Keytruda) alone when they progress provides the best results.
Another thing you may want to ask your doc about if your husband’s recurrence is only in sub q nodules is something called intralesional therapy. This is medication that is injected directly into melanoma tumors (therefore they must be accessible to the process – and sub q lesions certainly would be). We have found that when intralesional therapy is combined with systemic therapy results can be very good with the injected tumors being done away with along with “by-stander” lesions as well. There are many different products. Here are a zillion reports: https://chaoticallypreciselifeloveandmelanoma.blogspot.com/search?q=intralesional&max-results=20&by-date=true
Another option if your husband’s tumors are BRAF positive, targeted therapy may be a treatment option as well.
Here is a primer that addresses all of this that you might find helpful: https://chaoticallypreciselifeloveandmelanoma.blogspot.com/2017/08/melanoma-intel-primer-for-current.html
Hope all this is of some help. I know there are those on this board who have responded to immunotherapy after progressing on it and perhaps some of them will chime in. I wish you and your husband my best. Celeste