Understanding Jimmy Carter’s Surprise Cancer Turnaround: A Conversation with Jedd Wolchok

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Former US President Jimmy Carter

Former President Jimmy Carter announced this week that he is “cancer free” after receiving treatment for advanced melanoma. Photo Credit: The Carter Center.

Update: The immunotherapy drug that helped President Carter beat back cancer is yielding even more encouraging results. Data released on May 18, 2016 in advance of the annual meeting of the American Society of Clinical Oncology indicate that 40% of patients who received pembrolizumab (Keytruda®) as part of a large clinical trial are still alive three years later — a huge improvement over just a few years ago when average survival time for patients with metastatic melanoma was measured in months.

This week, former President Jimmy Carter announced that he is “cancer free” after receiving treatment for metastatic melanoma — a type of skin cancer that often spreads, or metastasizes, to other parts of the body. Mr. Carter’s cancer was discovered in his liver and spread to his brain.

In addition to surgery and radiation, Mr. Carter received a new immunotherapy drug called pembrolizumab (Keytruda®), which releases a brake on the immune system, empowering it to mount a stronger attack against cancer. The particular braking molecule targeted by this drug is called PD-1.

To get a better sense of what Mr. Carter’s surprise announcement means — especially for patients in a similar situation — we spoke with Jedd Wolchok, Chief of the Melanoma Service at Memorial Sloan Kettering.

Mr. Carter received three types of cancer treatment: surgery, radiation, and immunotherapy. At this point, can we say which was most responsible for his cancer-free outcome?

That’s a great question. My colleagues and I were just discussing this. I think it’s probably a contribution from all of the above. I don’t think it’s possible to ascribe the very favorable result to just one intervention. As time goes on, if he continues to have durable control of his disease, then I think we can be confident that immunotherapy played an important role.

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Can the combination of radiation and immunotherapy work together in a synergistic way to provide added benefit to patients?

There is that possibility. The hope is that when you kill a tumor with a tool like radiation therapy, you release cell debris that can trigger an immune response — similar to a kind of vaccination. Then, by blocking an immune checkpoint — in this case PD-1 — you allow that immune response to really take off.

Mr. Carter's case is a great example of how far the field has come in a relatively short period.
Jedd D. Wolchok immunologist and melanoma expert

We’ve certainly seen isolated examples of this phenomenon, called the abscopal response, with other immunotherapy drugs. I wrote a paper about this a couple of years ago with my MSK colleague Michael Postow. We’re now about to open a study using a combination of two immunotherapy drugs, ipilimumab and nivolumab, along with radiation for patients with melanoma. A lot of folks are really interested in this, and you can build a strong rationale for why it makes sense to use them together. But it has to be tested. 

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Are there times when it’s not possible to receive immunotherapy because of brain metastases?

We have a lot of issues yet to settle here. We know that the same medicines that can have a favorable effect on disease outside of the brain can have a favorable effect in the brain. There was a clinical trial that I participated in and published in Lancet Oncology about two years ago that looked at ipilimumab treatment in melanoma patients with brain metastases.

The challenge with brain metastases is that sometimes patients require corticosteroid treatments [which can suppress the immune system] to control swelling and symptoms. In the trial I referred to, the benefit of ipilimumab was seen only in the patients who were able to come off corticosteroids. So that’s an important consideration.

That’s why it’s good to do exactly what Mr. Carter’s physicians did, which was to control the brain metastases to the best of their ability — in this case with stereotactic radiosurgery — get him off the steroids as quickly as possible, and then initiate the immunotherapy.

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Is Mr. Carter’s experience representative of patients with metastatic melanoma and brain metastases?

It’s becoming more and more common. Mr. Carter’s case is a great example of how far the field has come in a relatively short period. If you turn back the clock ten years or so, people with melanoma and brain metastases had life expectancies that were measured in weeks and months. Now, there are patients in my practice who have had brain metastases and have been alive for years. And of course we hope the same is true for Mr. Carter.

I find it very inspiring that he’s been able to continue the important work that he’s engaged in without any side effects from treatment.

It’s also inspirational to patients, who can see that a devastating diagnosis doesn’t necessarily mean that you’re going to die immediately, or that the treatment is going to incapacitate you. Here’s a 90-year-old person not just living but fully active and engaged in activities that are making the world better for the rest of us. 

Pembrolizumab is one of two PD-1-blocking drugs approved by the FDA for the treatment of advanced melanoma, the other being nivolumab (Opdivo®). The five-year survival rate for patients treated with nivolumab is 34%, as reported last month at the annual meeting of the American Association for Cancer Research. Check back here on the MSK blog for more updates on progress in immunotherapy.

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Comments

James, thank you for reaching out. We consulted with an MSK radiation oncologist who responded that proton therapy would not be used for a patient with a PSA or 9.4 and at your age. If you would like to make an appointment with a Memorial Sloan Kettering physician about possible other prostate cancer treatments, please call our Physician Referral Service at 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment

How about PMP? Does this work on appendix cancer?

Hi Laurie, MSK currently has one clinical trial for appendix cancer, but it is not related to immunotherapy. You can find out more about it here: https://www.mskcc.org/cancer-care/types/appendiceal/clinical-trials

If you are interested in making an appointment with one of our experts, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more options. Thank you for your comment.

Is immunotherapy a possible treatment option (with radiation) for uterine cancer in lieu of chemotherapy for low grade tumors? Can MSK assist with this treatment?

Thank you all at MSK for your research and results. It is now two years since I was diagnosed with Melanoma. Dr. Callahan has treated me for the entire time at MSK and has been absolutely terrific; in addition to treating me with Keytruta she has been very supportive and professional. Two years ago when diagnosed I was sure that I had received a death sentence. I am still here and doing well. Thank

Dear Morris, we are sorry to hear about your diagnosis but are glad to know that you have felt well-cared for by Dr. Callahan. Thank you for sharing your thoughts and experience on our blog.

Good Morning -My spouse has stage IV melanoma that has spread to brain, lungs, liver and pancreas -He has had surgery to brain and lungs -He had 10 sessions of Radiation and currently immunotherapy every 3 weeks -We will not know if this has helped until repeat scans in December -He gets severe pruritis a fete immunotherapy so they prescribe Decadron by mouth -The oncologist told he he would have to be on Immunothrerapy for the rest of his life -Is this true? How can we afford this? What are the after affects of prolonged immunotherapy? Thanks Demy Blake

Dear Demy, we are sorry to hear about your husband’s diagnosis.

Immune checkpoint inhibitors are generally less toxic and easier to take than most chemotherapy drugs, however, because they are still fairly new and still being investigated, the long term effects are still unknown. In the short term, some patients do experience side effects. It’s important for your husband to continue to report any symptoms and side effects to his doctor so that he or she is able to help manage them. In some cases, patients are taken off immunotherapy if the
immune-related side effects become intolerable, but even then, the effects of the treatment can continue working after stopping treatment.

You may be interested in to know that there are organizations that provide financial assistance for patients in need of help with prescription costs, copays, and other medical expenses. Here are several resources that may be helpful:

The Patient Advocate Foundation allows you to do a focused search for organizations that meet your needs: http://www.patientadvocate.org/NURD/index2.php?application=financial

The patient website managed by the American Society for Clinical Oncology also provides a listing of organizations that offer financial aid for health-related needs: http://www.cancer.net/navigating-cancer-care/financial-considerations/f…

Cancer Care is another resource that you may find useful: http://www.cancercare.org/get_help/assistance/index.php

Thank you for reaching out to us.

My wife was recently diagnosed with angiosarcoma of the liver, involving the lymph nodes and peritoneum lining. Would a therapy using Keytruda be appropriate?

Hi Thomas, we’re sorry to hear about your wife’s diagnosis. There have been early studies suggesting that Keytruda may be effective against some types of sarcoma, but this is not an approved use for the drug. If your wife would like to come to MSK to learn about treatment options, including clinical trials, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment.

Good Morning-my sister in law had ocular melanoma 8 years ago. One of her eyes had been taken out, after that she was recovered. She was recently diagnosed with metastic liver melanoma. Many small and two bigger tumor was found on her liver. Can immunotherapy (Yervoy, Keytruda, etc.) help for her?

Thank You for your answer

Dear Skripeczky, we are sorry to hear about your sister-in-law’s diagnosis. We cannot make treatment recommendations on our blog without knowing more about her and her disease. If she would like to make an appointment to consult with one of our specialists and discuss possible next steps in her care, please ask her to call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

I have Stage IV Head and Neck cancer, positively testing for HPV 16. We found out recently that it has spread to my lung, and I will get my first treatment with Keytruda this week. I know that this drug has just recently been approved for Head and Neck. Was wondering how promising the results have been dealing with this type of disease, taking into consideration the HPV component. Also, I've been hearing rumblings about an HPV vaccine for patients already exposed to the virus. Does MSK offer a clinical trial for such a vaccine? Thank you kindly!

Dear Guy, based on its FDA approval, Keytruda appears to be effective in head and neck cancers that are HPV-positive as well as those that are not.

MSK does not currently have a trial looking at the HPV vaccine in those that have already been exposed to the virus, but we have other trials for cancers that are HPV-positive. If you’d like to learn more, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment, and best wishes to you.

My father was recently diagnosed with primary malignant melanoma of the duodenum. He is non-symptomatic as this was discovered during a procedure for an unrelated purpose. It has metastasized to the spleen and a few lymph nodes. There isn't much information available for this rare cancer. Does the origin of the cancer play a role in the treatment or clinical trial options for IV melanoma? What might be his options?

Dear Stacie, we’re sorry to hear about your father’s diagnosis. Usually, the part of the body where melanoma originates does not affect the treatment, but we recommend that you discuss this with his oncologist. If your father is interested in having a consultation at MSK, you can call 800-525-2225 during regular business hours or go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment, and best wishes to you and your family.

My father was recently diagnosed with gliosarcoma. Have there been any trials showing success using immunotherapy?

Dear Erik, MSK doesn’t currently have any trials specifically for gliosarcoma, but it’s possible that your father may qualify for a basket trial or other treatment based on the mutations in his tumor. You can read more about basket studies here: https://www.mskcc.org/blog/clinical-trial-shows-promise-basket-studies-…

If he would like to arrange for a consultation at MSK to discuss his treatment options, he can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment, and best wishes to you and your family.

My brother was diagnosed with metastatic melanoma in Jan. 2016. Has undergone surgery and radiation. Now in June, PET scan shows the spread of cancer to the lymph nodes near lungs as well as lesion in the liver. Oncologists are recommending Nivolumab before the BRAF test results. Is this the right method of treatment. Patient is 67 years old. Immunotherapy was not suggested immediately after surgery in FEb. radiation completed at the end of May . Was it wrong for us to wait for immunotherapy? Recommendation now by Indian doctors is 4 treatments of Nivolumab. What is your opinion. Thank you for your reply

Dear Sita, we’re very sorry to hear about your brother’s diagnosis. Unfortunately, we are not able to offer treatment advice on our blog. Thank you for your comment, and best wishes to you and your family.

Have you had any experience with using immunotherapy for metastatic endometrial cancer? And if so, does it require a specific genetic mutation? Thank you.

Dear Dale, we currently have several trials evaluating immunotherapy for endometrial cancer. You can learn more here: https://www.mskcc.org/cancer-care/clinical-trials/16-1491

and here: https://www.mskcc.org/cancer-care/clinical-trials/15-234

and here: https://www.mskcc.org/cancer-care/clinical-trials/16-490

In addition, if the cancer has a mismatch repair deficiency, the patient may be able to get pembrolizumab outside a clinical trial, because that drug is now approved for patients with that kind of mutation.

If you would like to learn more, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment.

Reading this article and seeing the influence Dr. Wolchok has had on his patients makes me immensely proud to be an employee here.

A year ago in June 2016 I was diagnosed with stage 3C metastatic ulcerated melanom,after first being misdiagnosed. I was referred to MSK and was operated on to remove the tumor and all my lymph nodes on my right side. Then Dr. Wolchok took over.I had never heard of melanoma but when I found out how aggressive it is I was devastated. Dr Wolchok took over my care and proceeded to treat me in every possible way. i had a PET scan numeros Cat scans and four weeks of radiation. I read everything I could on melanoma
and came to realize that the life span is usually short. Then Dr Wolchok started me on immunotherapy. I wish I could have had more treatments but the side effects stopped the treatments. I do hope that maybe I can continue with the treatments. I've gone through many traumas but I'm still here after 15 months thanks to Dr. Wolchock who saved my life more than once. It's because of him and Dr Weinstein that I haven't given up. It's a blessing to have him as my doctor.He is a genius but most of all a genuine human being.

D

Dear Christine, we’re very sorry to hear about everything you’ve been through. Thank you so much for your kind words. We will share them with your medical team. Best wishes to you.

My wife is currently in a trial with Keytruda for uterine cancer that's matastaticized to her T7, L4, L5, 4th ribs, lungs, vagina, 2 rumors on her skull that hadn't penetrated the brsin, 2 malignant pleural effusions. She's previously had surgeries (radical hysterectomy and corpectomy of T7), 6 rounds of chemo, approximately 35 to 40 radiation treatments, Gamma Knife, 2 Thorosenthesis, and is on 2ltrs oxygen 24/7. Plus she's now being treated for moderate lymphedema. Today we learned (via Pulmonary physician) that 2 lymph nodes in her left chest region are noticeably and significantly enlarged beyond normal. And an attempt today at a Thorosenthesis failed as the fluid as become gelatinous and is encased in several walled-off pockets of fibrous tissue that her body has "manufactured" to isolate that pleural fluid. OK, I shared all that to ask this: Could the significantly enlarged lymph nodes be an indicator (evidence) that the Keytruda is working and that this is some physical evidence that it's working. She's only had 2 Keytruda treatments (3 weeks apart with 3rd one today AFTER meeting with Pulmonary physician earlier)???

We asked the oncologist today if the enlarged lymph nodes was a positive sign or a cause for concern. No answer seemed to be forthcoming when we inquired. I'll attribute that to the fact that my wife apparently is the one single patient being given Keytruda for gynecologic cancer at this specific very large and reputable cancer center where she's being treated. Hopefully MKS has accumulated more research data relative to uterine cancer and just what those enlarged lymph nodes may indicate. Oh, and I'm not pitting one medical center against another here; Buy I'm curious and want every possible detail and nugget of data that's out there. Thanks.

Dear Ron, thank you for sharing your wife’s story. We recommend that you continue to discuss her case with her medical team. Best wishes to both of you.

Dear MSK, my niece is suffering from brain cancel, a tomato size brain tumour was removed from the brain, & cyber knife several small one. Her leg & arm were underwent operation added with steel plates as the bones were destroyed by cancel cells. Is keytruda treatment suitable for her? Thanking you in anticipation. Thong from Malaysia.

Dear Thong, we’re very sorry to hear about your niece’s diagnosis. Keytruda is currently approved for a number of cancers. Brain cancer is not one of them, but it’s possible that it may effective against a subset of brain cancer that has a mutation called microsatellite instability. You can learn more on the company’s website: https://www.keytruda.com/ Thank you for your comment, and best wishes to you and your family.

My 57-years-old brother, excellent state of health, suffered an acute CVA (stroke). CT showed metastatic lesion, biopsy-proven melanoma. His lungs and the spleen has nodules. Primary skin found. Devastating. Speech improved but hemiplegia persist after hematoma evacuation. I am thankful for your thoughts. He is a resident of Uruguay, South America. Keytruda is not on the formulary there.

Dear Jose, we’re very sorry to hear about your brother’s diagnosis. If he is interested in arranging a records review with experts at MSK or coming here for treatment, he can contact our International Center at international@mskcc.org, or go to https://www.mskcc.org/experience/become-patient/international-patients for more information. Thank you for your comment, and best wishes to you and your family.

Hoping to read positive immunotherapy treatment for kidney cancer which spread to adrenal gland, Had kidney and adrenal gland removed. A recent cat scan shows that it has now spread to T11 on spine.

My 57 yr old brother was diagnosed with melanoma first of March 2006. It came up as a lump under his arm. Dr said it was all clustered and contained in that one spot. He had surgery to remove that cluster; one sentinel node closest to the cluster tested positive. He did ipilimumab infusions for a year without side effects. His followups were all clear. But last Friday he learned that he has a spot on the lung. The Drs said it was small and that they had been watching it for a couple of his followups but thought it was scar tissue. They saw a change in it this time and that's when they told him it was melanoma. This Friday he is scheduled for brain scan and to start the pembroliazmab (sp?) infusions. The article said Pres Carter had radiation and the pembro- infusions. I understood it to say he had Gamma Knife on brain. Did he have any radiation on liver? If my brother's brain scan is clean, is only the pembro- infusion therapy best in his case or would it be more effective to combine radiation with it? (My brother is the 5th person in our family to be diagnosed with melanoma. He is being treated at the University of Alabama at Birmingham Cancer Center.)

Dear Carrie, we’re sorry to hear about your brother’s diagnosis and your family history. We recommend that your brother discuss combination therapy with his medical team. Thank you for your comment, and best wishes to you and your family.

I have stage IV melanoma and have been taking opdivo for 2 yrs with CT scans of chest, pelvis and abdomen along with MRI of brain being all clear. How long should I take opdivo before stopping. I have no real side effects from drug but some short of breath when climbing stairs. Started off with high dose yervoy but had to stop after 3 treatments, it ruined my pituitary and thyroid glands so I have to take hydrocortisone and synthyroid.

Dear Connie, we’re glad to hear that you’re doing well on Opdivo. You should discuss with your doctor the next steps. Thank you for your comment, and best wishes to you.

Are you still answering questions here? I have a brother with Stage IV Metastatic Melanoma. He had great success with tafinlar for one year, then switched to Opdivo and again great success with controlling lung tumors and others in his body, but NOT doing anything for a 5.2 cm liver tumor. Should he switch to Keytruda or other immunotherapy to deal with that? We are thinking about surgery to remove the tumor too to slow it's growth. Embolization is another option we think. Seems weird that Opdivo has worked on controlling and skrinking every tumor, especially the lung tumors and hasn't done a thing for the tumor on his liver. So far, normal function of the liver and blood tests normal. Please let me know what you suggest.

My husband had a nonmalignant tumor removed from his cerebellum last week at MGH by Dr. Pamela Jones. He also had one removed from his spinal cord seven years ago, which they controlled afterwards with radiation. Due to the pervasive presence of melanocytes in his brain observed during last week’s surgery (and he has four thickened areas on his meninges), he has been diagnosed now with Diffuse Leptomeningeal Melanocytosis, a very rare condition. Do you think there is any possibility that Keytruda or anything else that’s been developed lately would help him?

Dear Sarah, we’re sorry to hear about your husband’s recent surgery. Unfortunately we are not able to provide advice about medications on our blog. We recommend that you discuss this with his medical team. If he is interested in coming to MSK for a consultation, you can make an appointment online or call 800-525-2225. Thank you for your comment and best wishes to both of you.

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