A proof-of-principal phase II study shows that the white blood cell booster GM-CSF added to an increased dose of the immunotherapy ipilimumab extends survival for patients with metastatic melanoma.

More than two-thirds of patients were alive after one year of combination therapy vs. half of those treated with ipilimumab alone, a significant advance for metastatic melanoma.

Interestingly, the combination also appears to be safer for patients than ipilimumab alone — GM-CSF decreased some of the serious side effects of ipilimumab.

Both ipilimumab and GM-CSF work by activating the immune system to fight cancer.

Ipilimumab is a new treatment for advanced melanoma targeting CTLA-4, a protein that keeps immune T-cells in an inactive state. GM-CSF is a growth factor commonly used to boost white blood cell counts after chemotherapy or stem cell transplantation.

“This is the first randomised phase II study looking at the combination of ipilimumab and GM- CSF in any cancer,” said lead author F. Stephen Hodi, MD, an associate professor of medicine at Dana-Farber Cancer Institute in Boston, Mass. and principal investigator for this ECOG-ACRIN clinical trial. “The results of the E1608 study provide another important sign that immunotherapy can have a big impact for patients with advanced melanoma. At the same time, we still need to clarify the best way to apply these findings in everyday practice.”

In this study, 245 patients with metastatic melanoma who had undergone up to one prior treatment were assigned to receive ipilimumab plus GM-CSF or ipilimumab alone (at a dose of 10 mg/kg). The median follow up time was 13.3 months.

Tumour shrinkage rates were comparable in both arms (11-14 percent) but the overall survival rate was longer in the combination treatment arm: one year after the start of therapy, 68.9 percent of patients who received the combination were alive, compared to 52.9 percent of patients who received ipilimumab alone.

Patients who received the combination treatment had a 35 percent lower risk of dying compared with those that received ipilimumab alone.
In addition, the combination treatment was associated with fewer serious side effects compared to ipilimumab alone. The most significant differences were in lung and gastrointestinal toxicities. There were two possible treatment-related deaths in the combination arm vs. seven in the single- drug arm.

“This melanoma study builds upon the remarkable successes and advances we have seen for patients with advanced melanoma over the past two years,” said Lynn Schuchter, MD, ASCO spokesperson and melanoma expert.

The researchers noted that additional immune system boosters are being explored in early clinical trials, though the advantage of GM-CSF is that it improves both efficacy and safety of immunotherapy. The next step is to better define the role of GM-CSF in combination with other immune checkpoint targeting drugs, such as PD-1 and PD-L1.

This research was designed and conducted by the ECOG-ACRIN Cancer Research Group (formerly the Eastern Cooperative Oncology Group) and supported in part by the National Cancer Institute (Cancer Therapy Evaluation Program), Sanofi, and Bristol-Myers Squibb.

Source: ASCO