Despite the excitement surrounding cancer immunotherapy, most patients don’t respond to immune checkpoint inhibitors. There is, however, growing interest in combining these agents with chemotherapy, radiotherapy, and other treatments to boost their efficacy.1,2

A recent study of patients with advanced melanoma, for example, suggests that the combination of local chemotherapy and ipilimumab, a CTLA-4 inhibitor, may improve response rates and progression-free survival (PFS) over either treatment alone.3

Included patients had unresectable stage III or IV melanoma with regional metastasis in an extremity. They received isolated limb infusion (ILI) of 2 chemotherapies, melphalan and dactinomycin, in the affected limb, followed by ipilimumab 1 to 3 weeks later.

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Of the 26 patients in the phase 2 trial, 85% responded: 62% had a complete response; 58% were progression-free at 1 year. By comparison, studies have reported response rates of about 10% with ipilimumab monotherapy and about 50% with isolated limb infusion (ILI), although the response is typically not durable. Median PFS for melphalan and ipilimumab alone is 8 months and 2.9 months, respectively.

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“The most powerful thing is how well patients in this study responded and how many of them seem to be continuing to do well 5 to 6 years out,” Charlotte E. Ariyan, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, New York, told Cancer Therapy Advisor. Some of the patients are still progression-free and median PFS has not been reached, added Dr Ariyan, who is the trial’s lead author.

The patients experienced side effects common for limb infusion, such as swelling, and for immunotherapy, including diarrhea, rash, and fatigue. There was concern for possible synergistic toxicity going into the study, Dr Ariyan said, because of data suggesting that combining melphalan-based ILI with tumor necrosis factor alpha was associated with higher rates of limb amputation and other toxicity.4 “We did not see any side effects that were worse than normal,” Dr Ariyan said.