Combination Immunotherapy Produces Striking Results against Melanoma

By Jim Stallard,

Friday, May 8, 2015

A smiling physician in white coat talking to patient whose back is to the camera.

A clinical trial showed that giving melanoma patients a combination of two immunotherapy drugs, ipilimumab and nivolumab, resulted in significantly better outcomes than treating them with ipilimumab alone. One patient even had a grapefruit-size tumor disappear in weeks after a single treatment. Both drugs work — in slightly different ways — by removing a natural brake on the immune system.

  • Melanoma patients were given two immunotherapy drugs together.
  • The drugs were ipilimumab and nivolumab.
  • The two-drug combination worked better than ipilimumab alone.
  • This could be a significant advance in melanoma treatment.

Excitement continues to grow about new treatments that unleash the immune system to destroy cancer cells. In particular, great promise is being shown by immune checkpoint blockade (ICB) therapy — a class of drugs that boost the cancer-fighting powers of immune T cells, a type of white blood cell, by blocking certain receptor molecules on the cells’ surface.

MSK has played a leading role in developing this approach and testing these drugs, which include ipilimumab (Yervoy™), nivolumab (Opdivo), and pembrolizumab (Keytruda™). The therapies have produced remarkable results, eliminating cancer completely, as judged by scans, in some patients with highly advanced melanoma.

Now, two related reports by MSK researchers in the New England Journal of Medicine show that giving two of these drugs together can dramatically increase their effectiveness.

“Incredibly High Response Rate”

One study showed that giving both ipilimumab and nivolumab produced significantly better outcomes than ipilimumab alone in patients with advanced melanoma. The researchers tested the two-drug combination in 142 patients with metastatic melanoma who hadn’t yet received other treatment. The response rate — based on tumor shrinkage — was significantly higher in the patients receiving the combination therapy (61 percent) compared with patients receiving ipilimumab plus a placebo (11 percent).

 The effect of the combination therapy also proved more durable, as patients receiving both drugs survived longer without their disease progressing. Those receiving the combination therapy were more likely to have side effects (54 percent) than those receiving ipilimumab plus placebo (24 percent), but these side effects were manageable.

“The incredibly high response rate seen in this trial for patients receiving the combination therapy now lets us tell patients that they have a high chance of significantly shrinking their melanoma with this treatment,” says MSK medical oncologist Michael Postow, the report’s first author. “More research is needed, however, to know if it is necessary to give all patients this combination or if patients should receive drugs like nivolumab and ipilimumab in sequence.”

“We are excited about these results and believe they support the principle that rationally combining effective medicines is an approach to achieving better outcomes for patients,” adds medical oncologist and immunologist Jedd Wolchok, who led the study together with Stephen Hodi, an immunologist at the Dana-Farber Cancer Institute in Boston.

We are excited about these results.
Jedd D. Wolchok
Jedd D. Wolchok Lloyd J. Old/Virginia and Daniel K. Ludwig Chair in Clinical Investigation; Chief, Melanoma & Immunotherapeutics Service; Associate Director, Ludwig Center for Cancer Immunotherapy

The US Food and Drug Administration has approved ipilimumab and nivolumab separately as melanoma drugs but has not approved their combined use. More study is needed to see whether patients receiving the combination therapy ultimately live longer. Future trials also could help researchers determine the optimal number of treatments to be effective while minimizing side effects.

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Large Tumor Dissolves after Single Treatment

In addition to this study, NEJM also published a letter written by Dr. Wolchok and medical oncologists Paul Chapman and Sandra D’Angelo describing the remarkable effect of the ipilimumab-nivolumab combination in one patient whose melanoma had returned several years after surgery. The woman had a grapefruit-size tumor under her breast, but a single treatment with the two drugs caused the entire mass to disappear in only three weeks, leaving a cavity.

“This is one of the most astonishing responses I have seen,” Dr. Chapman says. “It reminds us of the potential power of the immune system if we can remove the brakes that keep it from attacking cancer cells.”

This is one of the most astonishing responses I have seen.
Paul B. Chapman
Paul B. Chapman Medical Oncologist

The researchers write that the potent effect illustrated by this single case also raises possible safety concerns. While no such problems have been reported thus far, Dr. Chapman notes that in rare cases, very quick tumor shrinkage could lead to complications. For example, a sudden hole in the heart muscle — a common site for metastatic melanoma — could hypothetically lead to bleeding.

“The irony that we are now concerning ourselves with an overly vigorous anti-melanoma response has not gone unnoticed,” he adds.

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Hi my husband has had a return of malignant melanoma after 16 years. it was in his left lung lower section, which they took out. then found it in his smaler section of liver again took it out. he went on chemo tab {tandao?} and inferon {retroviral} 9 months into treatment they found it growing on his heart and aorta, this was inopperatable and was a new growth while on treatment. they used an experimental drug called lilinumab {yervoy}with good results. as i understand this will buy us time as they are only outrunning the cancer. my question is
1. will he be able to use your drug should it become necesesary?
2. will it be availble on trials?.
We live in South Africa.
thank you.
Jean Parsons.

Jean, we're sorry to hear about your husband's recurrence. We are not able to answer personal medical questions on our blog, so you should discuss with your husband's healthcare team whether this treatment would be right for his situation. If you'd like to arrange for a consultation with MSK, you can contact our Bobst International Center at 1-212-639-4900 or go to for more information.

To find out whether this trial is available near you, you can go to This is a database maintained by the US National Institutes of Health that provides information on open clinical trials around the world.

Thank you for your comment.

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