Melanoma Treatment - Immunotherapy

Immunotherapy is a type of systemic (whole body) therapy used for treating metastatic melanoma or melanoma that has a high risk for recurrence (returning). Immunotherapy treats the whole body by attempting to activate a person’s immune system so that it will destroy any melanoma cells within the body.

Immunotherapy is prescribed and administered by a medical oncologist in a variety of ways, most commonly by using biologic agents that stimulate the immune system. Other mechanisms are currently under investigation in clinical trials and include vaccine therapy, intra-lesional therapy, stem cell manipulation and others.

View our Immunotherapy: Managing Side Effects webinar below, or view up-to-date recordings on a variety of melanoma treatments on our Educational Recordings page.

Immune Stimulants, FDA approved

Commonly prescribed immune stimulants include biologic agents such as antibodies, interferons and interleukins, which are administered in much higher doses than are usually present in the body. 

  • T-VEC (Imlygic®) received FDA approval in October 2015. Imlygic is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous and nodal lesions in patients whose melanoma has recurred after initial surgery. Imlygic is a genetically modified herpes simplex virus type 1 designed to replicate within tumors, causing tumors to rupture (cell death). Amgen's Assist® Program offers free medicines and co-pay assistance programs. 
  • Ipi + Nivo (Yervoy® (Ipilumumab) + Nivolumab®) combination received accelerated FDA approval in September 2015 based on improved response rates and progression-free survival in previously treated patients.
  • Nivolumab (Opdivo®) was approved in November 2015 as a first line therapy (previously untreated) for melanoma patients who do not have a positive BRAF V600 mutation. It was previously approved in 2014 for patients whose disease had progressed following ipilimumab and, if BRAF V600 mutation positive, also a BRAF inhibitor. It is the second anti-PD-1 drug to be approved for the treatment of unresectable (cannot be removed by surgery) or advanced (metastatic) melanoma, but the only anti-PD-1 therapy approved as a single agent for first-line use in patients with advanced BRAF V600 wild-type (not mutated) melanoma. In December 2017, Opdivo was approved (the first PD-1 inhibitor) as an adjuvant therapy in patients with lymph node involvement or metastatic disease who have undergone complete resection. This includes both BRAF mutant and BRAF wild-type patients. Opdivo is the first and only agent approved for the adjuvant treatment of melanoma based on head-to-head trial against an active comparator (Yervoy) with a proven overall survival benefit. Bristol-Myers Squibb's Access Support® offers financial assistance programs to help put treatments that your doctor has prescribed within your reach. Visit online or call 1-800-861-0048 from 8:00 A.M. to 8:00 P.M. EST, Monday through Friday. 
  • Pembrolizumab (Keytruda®) received accelerated approval in 2014 for demonstrating durable responses in patients whose disease has progressed following ipilimumab and, if BRAF V600 mutation positive, also a BRAF inhibitor. Randomized trials are in progress to assess the ability of pembrolizumab to improve time to progression and overall survival. Keytruda is the first anti-PD-1 drug to be approved by the FDA for melanoma. The Merck Access Program provides certain Merck medicines free of charge to eligible patients. Visit online or call 1-855-257-3932 from 8:00 A.M. TO 8:00 P.M. EST, Monday through Friday.
  • Ipilimumab (Yervoy®), which stimulates T cells, was approved by the FDA in 2011. It was the first drug in 13 years to be approved for the treatment of metastatic melanoma. Randomized trials have shown an improvement in overall survival in patients with either previously treated or untreated advanced melanoma. In addition, in October 2015, Yervoy was approved as adjuvant therapy in patients with Stage III melanoma. Patients and physicians should be aware that immune-mediated toxicities may be severe so good communication with your physician will allow early identification and successful treatment. Common side effects include: tiredness, diarrhea, itching and rash. Bristol-Myers Squibb's Access Support® offers financial assistance programs to help put treatments that your doctor has prescribed within your reach. Bristol-Myers Squibb also launched the Adjuvant Patient Program for Melanoma, offering free medication to eligible patients for the duration of treatment. Visit online or call 1-800-861-0048 from 8:00 A.M. to 8:00 P.M. EST, Monday through Friday. 
  • Peginterferon alpha 2-b (Sylatron®) is the FDA-approved standard treatment for patients with metastatic melanoma that has been surgically resected and that are at high risk for recurrence (i.e., for adjuvant therapy). Analyses of randomized trials of interferon used in an adjuvant setting show that it can lengthen the time of melanoma recurrence, but it does not appear to prolong survival.
  • Interleukin-2 (IL-2; Proleukin®) was the first immunotherapy to be approved for metastatic melanoma (1998) and was approved on the basis of long-lasting complete response. Randomized trials of IL-2 have not been conducted, so precise information on long-term overall survival is not available.

Checkpoint Inhibitors and Clinical Trials

A decade ago, the discovery of what is now ipilimumab launched a breakthrough in immunotherapy. Scientists discovered CTLA-4, a receptor on the surface of T cells that blocks the immune response by inhibiting, or stopping, T cell activation. An antibody was then developed - anti-CTLA-4 - that actually blocks this immune checkpoint protein, allowing the body's immune system to attack cancer cells, causing tumor regression. Since that discovery, ipilimumab and two PD-1 drugs, nivolumumab and pebrolizumab, have been developed and approved by the FDA for the treatment of metastatic melanoma. 

Of note in recent clinical trials: 

  • Nivolumab showed improved survival in previously treated patients when compared to DTIC (chemotherapy). Results from other randomized trials are pending. 
  • Pembrolizumab showed improved survival in both previously treated and untreated patients when compared to ipilimumab. Results from other randomized trials are pending. 

Side Effects of Immunotherapy Treatments

Starting or considering immunotherapy as a melanoma treatment option?

Take a look at our Immunotherapy: Managing Side Effects webinar, hosted by Mike Postow, MD of Memorial Sloan Kettering Cancer Center.  

*Webinar was recorded on June 18, 2018.

Side effects of immunotherapy treatments are not the same as side effects of traditional cancer treatments, like chemotherapy. Side effect are not an indicator that the drug is working or not working. It is very important to report all side effect to your treatment team as soon as you notice them. Most side effects can be managed if they are treated early, and this may allow you to stay on the treatment longer. Because immunotherapies are still relatively new, little is known about the long-term side effects of these treatments. The most common side effects of immunotherapies include:

  • Fatigue
  • Muscle or joint pain
  • Itching or rashes
  • Colitis or other GI problems

If you are newly diagnosed, it is important that you learn about all available treatment options