From the Experts: An Exclusive Look at Immunotherapy for Melanoma

Immunotherapy is a different approach to fighting cancer, and melanoma is one cancer type that this treatment is now approved for. As immunotherapy for melanoma has gained publicity, more patients are aware of it and are asking for more information about it.

What is Immunotherapy?

Immunotherapy boosts a patient’s own immune system to attack cancer. This approach is different than traditional strategies, such as chemotherapy and radiation, which attack both healthy cells and cancer cells equally.

According to Dr. Balch, “Health care professionals should understand that immunotherapy on its own does not treat cancer. Immunotherapy treats a deficient or abnormal immune system to treat the cancer. We want the patient’s immune system to recognize the cancer and attack it as a foreign invader.”From_Experts_Dr__Balch.jpg

Since immunotherapy is engaging a person’s own immune system, it mostly leaves healthy cells alone, resulting in different side effects compared with chemotherapy. The side effects of immunotherapy are in a category of autoimmunity, because these checkpoint inhibitors may break tolerance to “self-antigens.” Not losing their hair and not suffering from intense nausea can make a difference to patients in terms of quality of life. This, along with the fact that many people are living longer after receiving this treatment, are big draws for people to try this treatment.

“There are many reasons to use immunotherapy,” says Dr. Kaufman, who served as President of SITC from 2014-2016. “In addition to the different side effect profile mentioned, we often see more durable responses with immunotherapy than with chemotherapy. Although chemotherapy often works quickly by directly killing tumor cells, immunotherapy responses may occur later because it takes time to activate the immune system and then target the cancer. What doctors and professionals need to realize is this may result in a more delayed response, but typically the patient may actually be looking better and feeling better.”

Dr. Balch emphasizes that the health care industry is still learning about and evaluating this treatment as its application is being incorporated into standard care practices.

“We are still learning how immunotherapy works. More research needs to be done. We are not yet sure if it can be used alone or if it’s best in combination with other therapies. We need more trials involving patients with earlier stage disease.”

As more immunotherapy success stories are promoted in the media, patients are beginning to ask about it, and health care professionals should be prepared.

“Patients frequently request immunotherapy now,” Dr. Kaufman says. “Many people seek me out for that. I even had a patient with breast cancer come to me seeking immunotherapy. I told her I specialize in melanoma. She said, ‘I know, but you’re the only one I can get immunotherapy from.’”

People need to understand that immunotherapy isn’t a blanket strategy for every type and stage of cancer right now, but more clinical trials are being conducted to expand the reach.

Managing Side Effects

Since immunotherapy works differently than other cancer treatments, health care professionals need to be aware of immunotherapy complications and monitor closely, because early intervention can reverse the symptoms after the immunotherapy is stopped and steroids begun.

“Monitoring is key with treating patients with immunotherapy,” Dr. Balch says. “In fact, immunotherapy requires more monitoring, assistance and follow-up than any other cancer treatment option. It is important for health care professionals to understand that and to educate patients that professionals are available 24/7 to call and discuss their problems.”

Both Dr. Kaufman and Dr. Balch agree that health care professionals need to monitor and assist patients more closely because of the side effects. Although the side effects with immunotherapy are typically less common than with chemotherapy or radiation therapy, some side effects, usually in the form of an autoimmunity, can be severe and may need immediate attention.

“Professionals must educate the patient on how to recognize the early warning signs of a potentially serious side effect,” says Dr. Balch. “Patients need to not be afraid to call the doctor at the earliest signs of symptoms. With autoimmune responses, if caught early, 90 percent of the time, an autoimmunity [caused by the immunotherapy] can be reversed with steroids and by temporarily taking the patient off of the immunotherapy. If the patient waits too long [to report symptoms], it can cause irreversible autoimmunity and possibly death. Colitis can progress to death, and an attack on the endocrine system can be permanent. Patients need to be told whom to call after normal office hours if they have side effects. Stress to them that they should not be afraid to call. If they experience any symptoms that are beyond what is normal for them, they should call their doctor’s office immediately.”

It’s also important to realize that side effects can be delayed with immunotherapy, sometimes occurring even months after going off the drugs.

“Professionals need to watch patients closely when they are on immunotherapy drugs,” says Dr. Kaufman. “Patients on immunotherapy need to be monitored more, even as long as three to four months after treatment stops since both therapeutic responses and side effects may occur late.”

Determining Candidates

From_Experts_Dr__Kaufman.jpgIn determining which patients are good candidates for this treatment, Dr. Kaufman offers several tips.

“We need to look at the tumor and cells as well as the patient and his or her condition and age. One thing we’ve found in a newly published study is that older patients who’ve used immunotherapy are showing better survival rates than expected. It was believed that elderly patients, or those over 65-70 years of age, were not good candidates for immunotherapy and it wasn’t safe for them because their immune systems may not work as well. We are finding that thinking is wrong. Age is not a good reason for preventing a patient from trying immunotherapy.

“Candidates with autoimmune or suppressed immune systems or chronic steroid use typically have not been considered good candidates because they were excluded from clinical trial participation. But we are finding now that some people with these conditions can benefit from immunotherapy with minimal increase in potential adverse events. They may just need more monitoring than other patients.”

Dr. Balch explains that in clinical trials, patients with later-stage melanoma are responding better to immunotherapy.

“It is amazing that even in patients with advanced disease who have failed other systemic treatments, we are getting a strong response,” Dr. Balch says. “We must systematically evaluate the benefits and risks of immunotherapy, including combinations of therapies in a progression of clinical trials, starting with patients with advanced cancer to assess the risk versus benefits, and then progressing to a goal of increasing survival rates in surgical patients in the form of adjuvant or neoadjuvant therapy.”

Clinical Trials

Patients may have multiple fears about participating in clinical trials for immunotherapy for melanoma. It is important for health care professionals to help calm their fears.

Cost is one of the biggest fears patients may have with joining a trial. Encourage your patients to read the fine print in their consent forms, and discuss costs with their insurance company before beginning a trial.

“Immunotherapy is a revolutionary treatment and has shown amazing results, but because it’s so new, it’s very expensive. Even if the insurance company will pay for part, having to pay 5 percent to 10 percent of the copay can still be very expensive for the patient,” Dr. Balch says. “Also, patients need to know that many pharmaceutical companies will pay for the drugs if they are eligible for a clinical trial, which can be a significant incentive to consider.”

Patients often think if they don’t get the clinical trial drug they may risk not getting good treatment. Dr. Balch says he assures all of his patients they get the standard of care treatment, which has been built upon the results of clinical trials of the past.

Dr. Kaufman offers other reminders for professionals to share.

“Every drug used today was developed through a clinical trial,” Dr. Kaufman says. “That’s how we approve new drugs. Tell the patient they will get a lot of attention on a trial, and doctors can intervene more effectively. People often will say they don’t want to be a guinea pig. It’s important to remind them that these studies are reviewed by many groups and are very well-vetted. Trials are the best form of medicine today. They are the cutting edge of medicine now.”

More Research Needed

Both Dr. Balch and Dr. Kaufman agree that much more research is needed on immunotherapy.

“I’m involved in a study with the oncolytic virus therapy, talimogene laherparepvec (Imlygic). We’ve tested it in Stage III and IV, now we are working backward and testing it in Stage II melanoma,” Dr. Kaufman says. “We know that 50 percent of Stage II melanomas recur after surgery and often at a higher stage. So, in this study, we are looking at giving patients with Stage II melanoma oncolytic virus therapy six weeks before their planned surgery. We want to see if they will have an immune response to the cancer after the surgery. If successful, this could be one of the first neoadjuvant immunotherapy approaches for the treatment of melanoma.”

Other areas of research include immunogenomics and the value of immunotherapy drugs.

“Immunogenomics is going to be one of the hottest topics discussed over the next decade,” says Dr. Kaufman. “We don’t have a good handle on it now, and it may be more established for targeted therapy and precision medicine right now. We need to learn more about immune-related genes. We’d like to get to a place where we can predict a patient’s immune response to know if they are a good candidate for immunotherapy. [In the future,] we may be able to better predict a patient’s response to immunotherapy, which in turn may help us determine which immunotherapies to use first.

“Also, I want to mention the value proposition of immunotherapy drugs. Value incorporates clinical benefit, adverse event profile and economic costs. In addition, impact of patient quality of life should also be considered. Recently, there has been significant focus on the cost aspects of cancer treatment. While value is, of course, important, we have very little, if any, data on value for immunotherapy drugs. To date, most value analyses in oncology have focused on chemotherapy endpoints, which are completely different. Since patients on immunotherapy are living longer and have different side effects, the value proposition may be very different. These factors need to be weighed against the economic costs of the drugs. Furthermore, since immunotherapy works differently than chemotherapy, we need to consider if we can reduce the costs by reducing the amount of the drugs we are giving to patients. Some patients respond slowly, but the question of whether they need to stay on treatment waiting for the response is not clear. Maybe we can still get the response we want but at lower doses. Maybe patients don’t need to stay on the drugs as long to reach the same desired effect. We can’t approach immunotherapy with a chemotherapy mindset. We need to design end points and studies that are specific to immunotherapy and that are separate from chemotherapy. We are not there yet, but we need to get there.”

Photos: Dr. Balch & Dr. Kaufman
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