Rapid immune response following melanoma treatment leads to excellent prognosis

8 Feb 2021 17:00

The risk of recurrence for patients with metastatic melanomas is much smaller if their immune system starts cleaning up the tumor cells rapidly following immunotherapy, according to two studies published in Nature Medicine on February 8. “An early immune response appears to be an accurate tool to measure the efficacy and assess new therapies.”

Christian Blank, medical oncologist at the Netherlands Cancer Institute, has been involved in both Nature Magazine publications. “One of them concerns our own research. It reveals that patients who show an early immune response to immunotherapy before surgery – a treatment known as neoadjuvant immunotherapy – can rest assured that their illness won’t come back later.”

Rapid immune response, rarely a recurrence

The study investigated nearly 100 patients receiving immunotherapy for stage 3 melanoma before surgery. After the therapy, the immune system had to start attacking tumor cells. A rapid response appears to have an important predictive value, the study showed.

98% of the 71 patients who displayed a rapid response did not relapse within two to four years. Out of the small group of patients who did not show an immune response, two out of three saw a recurrence of the cancer. Blank is working on new treatments for these patients to improve their chances as well.

In the second publication, researchers compared different neoadjuvant therapies (therapies that precede surgery) in patients with melanomas, focusing on the relationship between patients’ response rates and their survival rates without recurrence. The research combined data from six different studies.

Almost no recurrence

The researchers compared four different therapies: two immunotherapies and two targeted therapies. Targeted therapy consists of drugs that inhibit tumor cell division.

The most important result: if  patients responded well to the neoadjuvant treatment (pathological response), there was almost no recurrence. This was most prominent in immunotherapy compared to targeted therapy. A plausible explanation is that immunotherapy activates the immune cells to attack the tumor cells, which continues to occur once the therapy is completed.

That could explain why even a partial pathological response to immunotherapy proved to have a highly beneficial long-term effect. Without this response, the prognosis for all therapies was significantly worse. Blank: “This is important news for drug administration agencies like the FDA or EMA: early immune response is an important indicator for the efficacy of the therapy.”

Good news

Blank emphasizes that it seems beneficial to deliver immunotherapy to melanoma patients before their surgery. “At this point, all different types of tumor cells that make up the tumor are still present. This optimizes the immune response activated by immunotherapy.”

These new results bring an important new dimension. “During surgery several weeks after immunotherapy, we can see whether the treatment elicited the desired response. And we now know what such a response really means. If the tumor has not disappeared or shrunk at the time of surgery, which happens to approximately 20% of patients, we know that the patient will need additional treatment after neoadjuvant therapy.”

Don’t operate right away

Blank will set up a large-scale clinical trial in the Netherlands and Australia based on the recently published data as soon as possible. Patients with stage 3 melanomas can participate in this neoadjuvant immunotherapy trial in several months at regional melanoma centers throughout the Netherlands. Blank urges medical and surgical oncologists not to operate on melanoma patients right away. Delivering immunotherapy six weeks before surgery seems to improve the outcomes significantly.

The study appearing in Nature Medicine as well as another clinical trial currently running in the Netherlands are part of the International Neoadjuvant Melanoma Consortium (INMC), of which Blank is a founding member. “Evidence is increasing. I want to make sure that neoadjuvant therapies will become the standard treatment as soon as possible. Together we can speed up the process. We design our trials after consulting each other so they can complement one another.”

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