In the News

On Cancer: Memorial Sloan Kettering’s Jedd Wolchok Describes Stunning Success of Cancer Immunotherapy in New York Times and Scientific American Features

By Jim Stallard, MA, Writer/Editor  |  Friday, May 2, 2014
Pictured: Jedd Wolchok Medical oncologist Jedd Wolchok

In the June 2 New York Times, Memorial Sloan Kettering oncologist Jedd Wolchok discussed how new cancer immunotherapies are allowing patients to survive longer than ever before. The interview took place at the 2014 meeting of the American Society of Clinical Oncology in Chicago.

In May 2014, Dr. Wolchok also described the stunning success of cancer immunotherapy in detail in an article for Scientific American.

Memorial Sloan Kettering medical oncologist Jedd Wolchok is featured in the May issue of Scientific American and on its website describing the new generation of cancer therapies that unleash the immune system to attack tumors. This new approach, which Memorial Sloan Kettering physician-scientists played a major role in developing, is producing stunning results when combined with standard anticancer therapies.

“I believe it is finally time to start thinking realistically about long-term remissions, even cures, because we can now combine standard therapies that target the tumor with immunotherapies that boost a patient’s own defenses,” Dr. Wolchok writes in “New Drugs Free the Immune System to Fight Cancer.” (Subscription is required for access to the full article.)

On its website, Scientific American also has a brief commentary about the feature, along with a video of Dr. Wolchok presenting a comprehensive overview of the new approach. In his article, Dr. Wolchok recaps the history of attempts to harness host defenses against cancer, which dates back more than 100 years. In the 1890s, William Coley, a surgeon at New York Cancer Hospital (the predecessor to Memorial Sloan Kettering), discovered that cancer patients who suffered from infections after surgery often fared better than those who did not. Dr. Coley hypothesized that the body’s defense system, which had been mobilized against the pathogen, could also affect the tumor. In the ensuing decades, scientists learned a great deal about the immune system’s workings without much success in translating their findings into cancer therapies.

Taking off the Brakes

Then in the 1990s, researchers discovered the importance of CTLA-4, a protein receptor on the surface of immune cells called T cells that puts the brakes on these cells and prevents them from carrying out attacks. Immunologist James Allison identified an antibody that blocks CTLA-4 and showed that turning off those brakes allows T cells to destroy cancer in mice. (Dr. Allison, who spent nearly a decade of his career at Memorial Sloan Kettering before leaving in 2012, is now at MD Anderson Cancer Center in Houston.)

Striking Clinical Success

Anti-CTLA-4 eventually became ipilimumab (YervoyTM), a drug approved in 2011 for the treatment of metastatic melanoma, the most deadly form of skin cancer. Dr. Allison and Dr. Wolchok helped guide the development of ipilimumab from the first laboratory studies through the late-stage clinical trials that led to the drug’s approval. Results of the latest clinical studies show that just over 20 percent of patients with metastatic melanoma treated with ipilimumab show long-term control of their disease, remaining alive for more than three years after treatment. (Previously, median life expectancy was seven to eight months.)

Researchers have found a second immune-system-braking molecule, called PD-1, which can also be blocked with antibodies. Immunotherapies targeting PD-1 have proved successful in treating lung cancer. “No longer can skeptical clinicians dismiss the approach as likely to be viable for only a few specific kinds of tumors,” Dr. Wolchok writes. “Odds are this approach will soon join chemotherapy and radiation as a standard treatment for many kinds of tumors.”

Dr. Wolchok’s research on immune therapies for melanoma continues, including a study last year that found more than half of patients with advanced skin melanoma experienced tumor shrinkage of more than 80 percent when given the combination of ipilimumab and the antibody drug nivolumab, which blocks PD-1.

Expanding Potential

Dr. Wolchok describes the optimism that has grown throughout the medical community over the last few years about immunotherapy treatments in patients with advanced leukemia and kidney and lung cancers. “Although immunotherapy is by no means a panacea, the recent advances may allow us to make significantly more progress against the later stages of cancer than we have been able to achieve in recent decades,” he writes.

Comments

What is your clinical experience with transfer factors? Are they useful? If so, why were they "forgotten" by the medical community after being discovered in the middle nineties? And why are they patented by a sole entity?

Maria, you can read more about transfer factors in our "About Herbs" database:

http://www.mskcc.org/cancer-care/herb/transfer-factor

There was an announcement by some researchers a couple of months ago that the efficacy rate of ipilimumab for mucosal melanoma patients was 6.7% - not exactly encouraging.

My question is has the efficacy rate of ipilimumab on mucosal melanoma increased significantly when it is combined with other pathway enabling drugs? Is ipilimumab still a drug just for ckit mutations?

Also, how do you "see" blocked pathways?

Thanks.
Mary

Mary, thank you for your comment. We consulted with MSK physician Richard Carvajal, who has conducted studies using ipilimumab for mucosal melanoma and he responds:

Although the response rate was modest in our published series -- 2/30 pts with an objective radiographic response (tumor shrinkage) -- these responses were quite durable. Furthermore, additional patients achieved durable disease stability, demonstrating that, as in cutaneous melanoma, a radiographic response is not necessary to predict meaningful clinical benefit. Given this, I believe that ipilimumab remains a reasonable treatment option as a single agent for those with advanced mucosal melanoma. However, if more novel treatment options, including combination studies, are available, I would strongly encourage participation.

I am terminal RCC.

For terminal patients PD-1 blockaders offer a chance of cure or remission for several types of cancer, yet they are not available in the U.S.A. and worldwide.

Thousands are dying unnecessarily as a result.

Surely these drugs should be allowed to terminal patients as of yesterday.

Though not as good, PD-1 blockaders for cancer can be regarded as penicillin is for bacterial infections.

Are we really going to go through years of Clinical Trials on each different cancer while terminal patients die?

Best regards,

Hi, Richard, we are sorry to hear about your diagnosis. You may be aware that our researchers have made many strides in the treatment of renal cell carcinoma. Unfortunately, it does takes many years to develop and test a drug before we know whether it will help patients, and we continue to do everything we can to get to that point.

You may be interested to know that do have a couple of trials open that are evaluating PD-1 in people with advanced or metastatic RCC. For more information, click on the following links:

http://www.mskcc.org/cancer-care/trial/12-159

http://www.mskcc.org/cancer-care/trial/12-147

We appreciate your comment and wish you all the best.

I submit prostaectomy in 23/10/2009.
i submit splectomy traumatic in 02/01/2012.
In 0109/2013= PSA= 0,018 .
I like opinion.

Ronaldo, unfortunately we are unable to answer specific medical questions on our blog. If you would like to make an appointment with a Memorial Sloan Kettering physician, please call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. Thanks for your comment.

Please thank Dr. Carvajal for his response, but what I was trying to get at was what Dr. Wolchok was referring to in his talk - that combining other treatments with ipilimumab increases the efficacy. It is very hard to get specific information on mucosal melanoma, so I beg your indulgence. Have you seen data showing that combining ipilimumab with other pathway enablers has any effect specifically on mucosal melanoma?

The presentation by Dr. Wolchok was fascinating and inspiring. I've watched it twice.

Mary, we followed up with Dr. Wolchok and he responded:

Dr Carvajal is currently conducting a trial of a CKIT inhibitor combined with ipilimumab (no data yet) and similarly I am conducting a study of BRAF inhibitor with ipilimumab, again too early to know results. Preclinical studies support the hypothesis that a combination approach is potentially more effective, but there is no human clinical trial data yet.

Is Sloan Kettering conducting immunotherapy clinical trials for metastatic papillary thyroid cancer with the BRAF mutation?

Dear Cheryl, these are all the clinical trials we are currently offering for thyroid cancer: http://www.mskcc.org/cancer-care/adult/thyroid/clinical-trials. You can also search the database of the National Cancer Institute for trials: http://www.cancer.gov/clinicaltrials/search. Thanks very much for your comment.

I had triple negative breast cancer. I did chemo for 4 treatments and Mammo-site. Is this an aggressive type of breast cancer?

June, thank you for your comment. Yes, triple negative breast cancer is generally an aggressive subset of breast cancer. You can see more information about this type of tumor at

http://www.mskcc.org/cancer-care/adult/breast/characterizing-tumor

I'm a huge admirer of Dr Wolchok work and I'm very far away (Argentina) so I try to read and watch everything I can, about his research, and maybe share it with others.
So.
1. Here it's my copy of the SciAm article (full): https://drive.google.com/file/d/0B9Eo84kGLvX0YjR5X0JKUWRoLWs/edit?usp=sharing
2. He was in a Tedx talk, "Pushing Boundaries", at TimesSquare this past May 2nd 2014. Here I'm sharing its conference "The Immune System vs. Cancer:
https://www.youtube.com/watch?v=CcA7E-nch0k
(you can watch it too at http://tedxtimessquare.com/?page_id=1632 , but his is in the middle of those from all the other speakers from that day; for easier watching, I prepared that separate video).
My best to Dr Wolchok, from far away : )

I am in Dr. Wolchoks study with the PD1 & Ipimilumiab (spellings off I know) and it has worked! I have had 2 tumors at once. Surgery after they shrunk drastically showed 1 dead & 1 near death. It has been over a year for me now and all my scans come up clear. If you have any doubts get into sloan and chat with Dr. Wolchok. The man is a genius and very awesome to talk to. If ypur wondering I was Melanoma Stage 3. THANKS TO DR. WOLCHOK, DR. ARIYAN & DR. COIT...you guys are amazing!!

Are there any immunotherapy trials for advanced stage ovarian cancer?

JS, here is a listing of all clinical trials we have open for patients with ovarian cancer (there don't seem to be any evaluating immunotherapy at this time): http://www.mskcc.org/cancer-care/adult/ovarian/clinical-trials

You may be interested in searching the National Cancer Institute's database for immunotherapy trials open in your area, by keyword: http://www.cancer.gov/clinicaltrials/search

I hope this is helpful - thank you for reaching out to us.

Is there any immunotherapy trial for hormonoresistant advanced prostate cancer?

Saber, here is a link to our clinical trials currently open for men with advanced castration-resistant prostate cancer (one of which is evaluating an immunotherapy): http://www.mskcc.org/cancer-care/adult/prostate/clinical-trials?keys=resistant&phase=All

Thank you for reaching out to us.

I am a very good friend of professor zaaroor from Israel and his daughter dafna who gave me your name
My husband has melanoma stage 3 c. He is with dr Steve o'day and is entitle to receive pd1. The reason is he has cll and couldn't participate in clinical trials! And now they opened the use of pd1 to such patience.Right now he is in his second infusion of yirvoy, but after that o'day plans to continue with pd1. Would appreciate your opinion. Best regards Roni

Roni, we are not able to answer individual medical questions on our blog. If your husband would like to consult with one of our doctors about arranging a records review or an appointment in New York, you can contact our Bobst International Center at 1-212-639-4900 or international@mskcc.org or go to http://www.mskcc.org/cancer-care/international-patients for more information. Thank you for your comment.

Are there any immunotherapy trials for advanced rectal cancer at Sloan Kettering

Brenda, thank you for reaching out. Here is a link to a Memorial Sloan Kettering trial that may be appropriate (there is contact information included in the trial description so you can speak with someone to find out about eligibility):

http://www.mskcc.org/cancer-care/adult/colorectal/clinical-trials/12-224

In addition, if you would like to make an appointment with a Memorial Sloan Kettering physician, please call our Patient Access Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. Thanks for your comment.

Are there any immunotherapy treatments or trials for advanced intrahepatic cholangiocarcinoma? Thank you. Best regards Charlotte

Charlotte, thank you for your comment. Currently Memorial Sloan Kettering has two clinical trials for this disease but they are not immunotherapy:

http://edit.mskcc.org/cancer-care/clinical-trials/clinical-trial?keys=intrahepatic+cholangiocarcinoma&field_trial_diseases_value=All&phase=All

You might also check the government's listing of clinical trials at:

https://clinicaltrials.gov/

What recommendations would you have for a healthy woman in early 30s, HER2 positive breast cancer who responded well to Herceptin therapy. Later diagnosed with a metastatic brain tumor that was completely excised; followed by radiation and Tykerb and Xeloda regimen. What would be the next step? Your thoughts, suggestions, and comments are appreciated.

Cheryl, unfortunately we can't give personal medical advice on our blog. To make an appointment with one of our experts, you can call 800-525-2225 or learn more here: http://www.mskcc.org/cancer-care/appointment. You may also want to see if the hospital where you were treated has a survivorship program or other sorts of follow-up services for people who have completed treatment.

I have been using transfer factors different patients. I have found it to be effective in most of our cancer patients. It is also effective for our HIV and even to the simplest boil. I always couple the treatment with proper nutrition or nutritional supplements if the patient can afford. I have seen patients get cured without chemotherapy, radiation or surgery. Can MSKCC intensify the studies and do more documentation for this? Besides a two month study is not practical. it has to be a long term study to really see effects on these. We have been treating patients for as long as two years to really see the full effect. Though great improvement is already seen in two to three months.

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