Medical oncologist Jedd Wolchok pioneered a combination immunotherapy treatment for patients with advanced melanoma that has just been approved by the FDA.
Today, the US Food and Drug Administration (FDA) approved the immunotherapy combination nivolumab (Opdivo®) plus ipilimumab (Yervoy®) for use in patients with metastatic melanoma. This is the first-ever combination immunotherapy to receive approval by the FDA. To learn more, we spoke with Memorial Sloan Kettering medical oncologist and cancer immunologist Jedd Wolchok, the physician-scientist leading this work.
Where did the idea to combine nivolumab and ipilimumab come from?
The idea to combine these two immunotherapies emerged after we had strong scientific evidence that each one was effective by itself. We had worked with ipilimumab for several years, but it appeared to benefit only 20 percent of patients. Nivolumab had shown early signs of good activity for newly diagnosed patients, and a similar medicine (pembrolizumab) had activity in disease that was refractory — which means it wasn’t responding to treatment — or relapsed after initial treatment with ipilimumab. Then there were lab experiments that showed the two strategies worked well together. So in 2010, before either drug had FDA approval on its own, we embarked on the phase I trial testing the combination of the two. Ultimately the results showed a 53 percent response rate — quite a bit higher than we expected. For some patients, it was very dramatic. We would get scans back showing that virtually all of the disease had gone away.
After the first 15 to 20 people, we began working with our colleagues at Bristol-Myers Squibb to design phase II and then phase III trials. The results of the phase II trial were presented in April during a meeting of the American Association for Cancer Research and published in the New England Journal of Medicine by my colleague Michael Postow, who was a fellow in our group back when we did the phase I trial. This past June, I presented the phase III results at the American Society of Clinical Oncology annual meeting.
Back to topSo it took five years from start to finish. That’s fast!
Yes, to me that’s the most exciting thing. We’ve gone from presenting the initial data to rolling this treatment out for standard use in quite a reasonably short period of time.
Back to topWhat do you attribute this rapid pace to?
A few things. First, we saw an unmistakable signal when using the combination in patients. And these patients had a high unmet need — they didn’t have many other treatment options. Then there was exceptional coordination between the FDA, the academic investigators, and our industry colleagues. This example actually shows that drug development doesn’t necessarily require enormous studies with many years of follow-up. It’s possible to move at a much faster pace when everyone is collaborating effectively.
Back to topCan you describe the moment you knew this combination was going to be a success?
By my desk, I have an email pinned up from one of our pathologists dated July 7, 2010. It has the pathology results from one of the very first patients to receive the regimen. This patient had a very large lump on his side, and every time he came in it got smaller and smaller. But after four doses, it wasn’t completely going away, and we wondered if the disease was resistant to treatment.
One of our surgeons, Mary Sue Brady, removed the lump, and I was so very eager to know what was going on that I waited outside the operating room while it was being removed. “What did it look like?” I asked her colleague when she came out. “Oh, just metastatic melanoma,” she said, and I was so disappointed.
Then, a week later, I got an email with the pathology report.
Completely necrotic tumor surrounded by immune cells — the histologic picture of treatment success.
In other words, the tumor was dead. I smiled, I printed it out, and it’s been hanging on my cork board ever since. And that was our second patient to receive the combination.
Back to topAs someone who has dedicated his career to improving treatment for people with advanced melanoma, what does this mean for you?
When I joined the MSK faculty in 2000, the median survival for patients with advanced melanoma was seven months with the best treatment available at that time. Now we are routinely hearing about two- and three-year survival. In the last study we did, we were seeing patients with 14 months of progression-free survival — which means they lived with their disease but it didn’t grow or spread — and that’s just an estimate. It gives you a flavor for how rapidly the expectations for life have changed, and it happened all within the first part of just one person’s career.
Back to topHow has MSK’s focus on collaboration and translational research made this advance possible?
MSK has had a tradition of excellence in treating melanoma and in developing novel therapies. Immunotherapy has actually been a focus at MSK since the late 1890s, and we have been a part of all the major immunotherapy advances throughout the history of cancer treatment.
For this particular regimen, we were among the very first to use this novel combination, we designed the pivotal studies that have supported approval, and we’ve done some of the most important research to understand who benefits and why. We haven’t answered all the questions yet, but we look forward to pursuing the answers and understanding how we use this regimen to help even more patients, for example those with lung cancer and other cancer types.
Back to topComments
Anonymous
Oct 1, 2015 • 5:34 PM
Anonymous
Oct 3, 2015 • 11:08 AM
If you’d like to arrange for a consultation with MSK’s experts to discuss treatment options for your wife, please call 800-525-2225 to make an appointment or go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment.
Anonymous
Oct 9, 2015 • 1:22 PM
Memorial Sloan Kettering
Oct 9, 2015 • 6:16 PM
In reply to Is there anything about this… by Anonymous
Dear Linda, thanks so much for your question. The treatment is used for disease that has already recurred. Our doctors recommend that people who’ve been treated for melanoma have regular check-ups to monitor for recurrence and the development of other skin cancers.
You might also be interested to learn about our new 3-D total body photography program: https://www.mskcc.org/blog/3-d-photography-helps-early-detection-patien….
Thanks for your question!
Anonymous
Oct 10, 2015 • 9:06 AM
Memorial Sloan Kettering
Oct 12, 2015 • 2:19 PM
In reply to My dad is stage 4 melanoma. … by Anonymous
Lore Rasch
Nov 4, 2015 • 5:19 PM
Janet
Apr 21, 2016 • 4:03 PM
My brother (lives in Denver) had a melanoma removed from his calf in 2013 with a follow up xray each April. About a month ago he felt a lump in his groin. He went to the doctor and they did: Chest xray, ct chest/abd/pelv, us abdomen, mri brain and tested his liver. The cancer returned to the chest, abodmen and in the groin is a tumor. His brain and liver are clean. They are now testing him for a gene to get him into a trial and we are also trying to get him to Dr. Rene Gonzalez in Denver. Are we doing everything we can?
Dear Janet, we are sorry to hear about your brother’s diagnosis. Only a physician who has examined your brother and reviewed his medical records can comment on whether all appropriate options are being explored. If he would like to make an appointment with one of our specialists for a second opinion, please ask him to call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.
Stephen Allison Wald
Apr 27, 2016 • 3:08 PM
Dear Dr. Wolchok, Our daughter, Jennifer, has courageously fought neuroendocrine cancer for 13 years, via uncounted major surgeries, including a Whipple, two liver transplants, liver and pancreas resections, hip and femur replacements.
She has not had immunologic-based chemotherapy. She's experiencing multiple tumors around her body...fortunately, not yet in her lungs. No treatment options remain.
We can't help but wonder what the dangers might be for her to be treated with the combination protocol?
Godbless your pioneering work.
Memorial Sloan Kettering
Apr 27, 2016 • 5:00 PM
In reply to Dear Dr. Wolchok, Our… by Stephen Allison Wald
Dear Stephen, we are very sorry to hear about your daughter. She has been through so much. Unfortunately, our doctors can’t offer specific medical advice on our blog, but if you are interested in consulting with one of our specialists to discuss whether there are treatment options (including clinical trials) that may not yet have been explored, please call our Physician Referral Service. They can answer your questions and can be reached at 800-525-2225. Thank you for reaching out to us.
Sally
Jun 9, 2016 • 7:29 PM
Dear Sally,
While this particular combination of immunotherapy drugs is not being tested in leukemia, several other immunotherapy approaches are. These include CAR T therapy, other checkpoint inhibitors, and stem cell transplants. Memorial Sloan Kettering has open clinical trials in all of these areas. If you would like to learn more, please visit https://www.mskcc.org/cancer-care/clinical-trials/search.
Thank you for your comment.
Linda Richardson
Jun 24, 2016 • 10:21 PM
Dear Drs, I have stage 4 mucosal melanoma. I've had my rectum and anus removed. I'm only 55 and have children and myself that are horrified. I want and need to live. I've had 6 doses of keytruda with mixed responses. I want to come there to see your melanoma specialists as I'm not sure what's going to happen. What about the combination of the two drugs or T cell therapy. I want the drastic treatment so I have a chance to live. I have 3 rumors in my pelvic area, there not going away, please researchers and melanoma experts at you center...help me, don't let me lose my children to this disease. You have more options than anyone there. Accept me and me live thru this, please, Sincerely, LindaRichardson
Memorial Sloan Kettering
Jun 26, 2016 • 8:09 PM
In reply to Dear Drs, I have stage 4… by Linda richardson
Linda, we’re very sorry to hear that you’re going through this. Please contact our Physician Referral Service during regular business hours at 800-525-2225. You can go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment.
DOUG ENGLR
Aug 12, 2016 • 10:39 AM
Memorial Sloan Kettering
Aug 16, 2016 • 9:46 AM
In reply to Is there an online source… by DOUG ENGLR
Doug, you might want to check out MSK’s online community, Connections. Patients there can share experiences about a range of cancer treatments and get advice from other patients and caregivers. It is open to all cancer patients, not just those being treated at MSK. To learn more, you can go to https://www.mskcc.org/experience/patient-support/counseling/groups/conn…. Thank you for your comment.
Stacy Hawn
Aug 17, 2016 • 7:39 PM
Memorial Sloan Kettering
Aug 18, 2016 • 4:57 PM
In reply to I am stage 3a melanoma. No… by Stacy Hawn
Stacy, thank you for reaching out. We recommend that you speak with your healthcare team about whether this combination therapy would be appropriate for you. If you are interested in consulting with one of our specialists, please call our Physician Referral Service. They can answer your questions and can be reached at 800-525-2225.
Valerie O'Brien
Sep 29, 2016 • 9:25 PM
My sister has neuroendocrine cancer and does not have the somatostatin receptor usually targeted in treatment. We found out today the chemo she has had for the past few months did not work and she has two tumors on her adrenal gland. Is anyone testing this combination (Nivolumab and Ipilimumab) therapy for neuroendocrine cancer?
Memorial Sloan Kettering
Sep 30, 2016 • 11:21 AM
In reply to My sister has neuroendocrine… by Valerie O'Brien
Dear Valerie, we are sorry to hear about your sister’s diagnosis. You did not indicate whether she has gastrointestinal neuroendocrine cancer or pulmonary neuroendocrine cancer, so we have included links to both disease guides on our site for you to get more information about treatment options.
Pulmonary Neuroendocrine Tumors: https://www.mskcc.org/cancer-care/types/pulmonary-neuroendocrine-tumors
Gastrointestinal Neuroendocrine Tumors: https://www.mskcc.org/cancer-care/types/gastrointestinal-neuroendocrine
And here’s more information about Adrenal Gland Tumors: https://www.mskcc.org/cancer-care/types/adrenal-tumors
If she would like to make an appointment with one of our specialists to discuss her treatment options, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.
Maor
Oct 13, 2016 • 5:05 AM
Dear Drs.
My brother is 43 years old.
Amonth and a half ago He was started to hobble on his left foot he got several medical tests and MRI the diagnosis melanoma with metastatic stage 4 to the brain.
he started for 5 times radio therapy FSR
to his brain every time a half hour radiation
also he got thrombosis on his left foot treated by Clexane injection twice a day
on the 11/10/16 my brother strat immunotherapy treatment by Opdivo for every 2 weeks
I would like to know how can my brother gets the treatment of the combinziia of Opdivo and YervoY ??
Please your kind help asap.
We are from Israel and my brother is treated in Sheba Medical Center
Thanks in advance !
Dear Maor, we are sorry to hear about your brother’s diagnosis. If you would like to arrange for one of our specialists to conduct a medical records review by mail or an in-person appointment to discuss possible treatment recommendations, please contact our International Center at international@mskcc.org. To learn more about our services for patients who live outside of the United States, please visit https://www.mskcc.org/experience/become-patient/international-patients. Thank you for reaching out to us.
David Sochol
Oct 29, 2016 • 11:22 PM
Memorial Sloan Kettering
Oct 31, 2016 • 10:54 AM
In reply to Does this (ipi and novi) … by David sochol
Dear David, the ipi + nivo has been studied in SCLC, where it has shown promise, but the combination is not FDA approved for this indication, or NET. You can read more about some clinical trial results here: https://am.asco.org/pd-1-agents-show-promise-small-cell-lung-cancer
To learn about a current, ongoing trial of this combination, please visit: https://www.mskcc.org/cancer-care/clinical-trials/15-303. If you have any questions about these studies or would like to make an appointment with one of our specialists, please call our Physician Referral Service at 800-525-2225.
Thank you for reaching out to us.
Sol
Jan 6, 2017 • 5:59 PM
my father was a patient there he recently died feb 10 2016. the duo treatment didn't help because of his immune system because of HIV. are you guys trying to also find ways to treat HIV patient another way to boost the immune system. by the way memorial Sloan gave the best treatment to my father but his immune was weak and stage 5. And I thank you for that.
Dear Sol,
We’re sorry to hear about your father, but we are glad to hear he was well
cared for. To answer your question, yes, researchers are very interested
in using new immunotherapy approaches as a way to fight infectious
diseases like HIV. Here is one study that MSK researchers are pursuing:
https://www.mskcc.org/cancer-care/clinical-trials/16-1286
Thank you for your comment.
Jen
Feb 17, 2017 • 7:24 PM
We just found out that my husband has melanoma in lungs. He had melanoma in 2010 on his arm. It was removed, no treatment was done then. His mass is 7.4by 5.4 cm. We schedule appt to melanoma doctor next week. We will do pt scan on Monday before visit. His byopcy cells were sent to lab for mutation DNA, hopefully today. What will be your recommendations?
Dear Jen, we’re sorry to hear about your husband’s diagnosis. If he would like to arrange for a consultation with a doctor at MSK to discuss his options, 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 and your husband.
Linda
Mar 14, 2017 • 3:00 PM
Dear Linda. we’re sorry to hear about your sister’s diagnosis and the side effects from her treatment. Unfortunately we are not able to offer medical advice on our blog, so we are not able to say what treatment may be appropriate for her. We recommend that you discuss this with her healthcare team. If she wants to come to MSK for a consultation, she 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.
Lisa Gutschow
Mar 21, 2017 • 3:22 PM
Dear Lisa, we’re sorry but we are not able to answer individual medical questions on our blog. We recommend that you discuss this with your healthcare team. If you’re interested in having a consultation with an MSK doctor, 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.
Kimberly M
Jun 15, 2017 • 6:48 PM
Hello!
Recently had a mole removed from my right shoulder, it was stage 2. Melanoma. Tumor removed with wide margins, clean border. The Sentinel Node was Removed under arm and positive for melanoma, but it was very small. PET scan clear, MRI clear. I've read a lot about axillary lymph node dissection and really concerned for lifelong problems. I feel as if I already have issues from the sentinel node was removed. Are there any alternatives to this standard protocol? They want to do the axillary lymph node dissection with additional treatment TBD. My concern is that im already prone to edema at times and why set myself up for more problems down the road? With all this technology, there are no alternatives to check and see if they are positive? Best, Kim
Dear Kimberly,
We are not able to make treatment recommendations for individual patients on our blog, since each case is different. However, you may be interested in this recent blog post about a study that compared immediate lymph node dissection to a watch-and-wait approach: https://www.mskcc.org/blog/definitive-study-shows-people-melanoma-do-no….
If you would like to consult with an MSK doctor, we encourage you to make an appointment at 800-525-2225 or request an appointment online at https://www.mskcc.org/experience/become-patient/appointment. Thank you for your comment.
Patty Torrilhon
Oct 8, 2017 • 3:51 PM
My husband was diagnosed 6 months ago with primary anal/rectal malignant melanoma. A surgeon perfomed an excision of the 3cm tumor. Cancer cells remained in the muscle wall. He was scheduled for 6 chemo treatments (cisplatin) which had to be terminated after immediate damage to his kidneys. He then received 33 radiation treatments. During this time he suffered from a severe body rash which was biopsed with a probable drug reaction diagnosis. He was given prednisone which worked at a high does, but returns as soon as the medication stops. He has told that his prognosis is poor and that his cancer cells do not have the characteristics needed for immuno-therapies? He is scheduled for a follow up PET scan in November. We have been told that this cancer is extremely rare and so options are not very available. Do you have suggestions for us? Thank you.
Memorial Sloan Kettering
Oct 9, 2017 • 8:31 AM
In reply to My husband was diagnosed 6… by Patty Torrilhon
Dear Patty, we’re very sorry to hear that your husband is going through this. If he would like to come to MSK for a consultation, and to learn if he would qualify for any of our clinical trials, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information. If you are not in the NYC area and not able to come to MSK, you may want to seek out a National Cancer Institute-designated cancer center that is closer to where you live. You can find a list at https://www.cancer.gov/research/nci-role/cancer-centers
Thank you for your comment, and best wishes to you and your husband.
Backindaday
Jul 9, 2018 • 9:13 AM
Memorial Sloan Kettering
Jul 10, 2018 • 5:42 PM
In reply to it seems to me, that this… by backindaday
This drug combination has been use in people with MS, but it’s important for people to discuss the potential risks and benefits with their doctors. If you are interested in coming to MSK for a consultation, you 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.
MONTE JEFFERY
Dec 19, 2018 • 1:47 PM
Memorial Sloan Kettering
Dec 19, 2018 • 4:10 PM
In reply to What risks does a patient… by MONTE JEFFERY
Does this treatment apply too choroid melanoma as well?