Immunotherapy Offers New Strategy for Treating Sarcoma

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Enlarged microscopic image of blue-green immune cells surrounding one blue cancer cell.

Immune T cells surround a cancer cell. Researchers are investigating ways to stimulate these immune cells to fight sarcoma. (Source: Alex Ritter, Jennifer Lippincoll Schwartz and Gillian Griffiths, National Institutes of Health)

Update: This story was originally published on July 28, 2016, and has been updated with new information.

Immunotherapy, which harnesses the power of the immune system to fight disease, has recently shown impressive results in the treatment of multiple cancers. The Food and Drug Administration’s approval of a class of drugs called checkpoint inhibitors has dramatically improved therapeutic options. People with melanoma, lung cancer, kidney cancer, bladder cancer, leukemia, and other cancers may benefit from these drugs.

Researchers at Memorial Sloan Kettering are hoping that this immunotherapy success can be applied to the treatment of sarcomas as well. These rare cancers grow in the body’s connective tissues, including fat, blood vessels, nerves, bones, muscles, and cartilage.

We spoke with MSK medical oncologist Sandra P. D’Angelo about the current state of research, including which clinical trials at MSK are under way or planned to open soon.

Why use immunotherapy as a treatment for sarcoma?

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The immune system can help fight cancer.
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Sarcoma is a devastating disease for which we need more-effective therapies. Sarcoma has more than 50 distinct subtypes, and the threat of metastasis can be high. Depending on the type of sarcoma and its initial size, the disease can spread in some patients who are diagnosed. Men and women whose cancer has spread to other parts of the body often respond to treatment but the duration of benefit can sometimes be short and the side effects can sometimes be tough.

With conventional treatments such as chemotherapy, or even newer targeted therapies, we try to treat the tumor. But it will likely prove difficult to develop a single therapy that would work across all of the sarcoma subtypes. Each of these diseases may behave differently and require distinct treatment approaches.

Immunotherapy is an appealing option because it’s designed to empower the immune system to fight many different types of cancer, not just one. My colleague Jedd Wolchok and I worked on immunotherapy treatment for melanoma. He takes the view that it’s often better to treat the person and let their own body treat the tumor.

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What types of immunotherapy are now being investigated for sarcoma?

The main approaches involve checkpoint inhibitors and adoptive T cell therapy. Checkpoint inhibitors are drugs that block specific proteins on the surface of immune T cells. This releases a natural brake on the immune system, allowing it to attack the cancer. Adoptive T cell therapy involves removing T cells from patients and modifying the cells in a way that enables them to recognize and attack specific molecules on the surface of cancer cells. MSK has led the way in using both of these approaches to treat cancer.

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How is checkpoint inhibitor–based immunotherapy being tested against sarcoma at MSK?

The checkpoint inhibitors we are investigating include the drugs ipilimumab (Yervoy®), nivolumab (Opdivo®), and pembrolizumab (Keytruda®), which we’ve already seen be effective in multiple cancers.

Ipilimumab targets a protein called CTLA-4. In earlier clinical studies, it seemed to have a very minimal effect when used alone against selected sarcomas. The latter drug, nivolumab, targets a different protein, called PD-1. We were struck by the deep and rapid responses in people with melanoma when ipilimumab was combined with nivolumab. We think combination immunotherapy will benefit more people with sarcoma. Much of our efforts are focused on identifying the best drugs to combine for patients.

I led a national phase II clinical trial testing the combination of these drugs in people with metastatic sarcoma. We found that nivolumab and ipilimumab are effective in certain sarcoma subtypes. These include undifferentiated pleomorphic sarcoma and myxofibrosarcoma (both types of liposarcoma) as well as leiomyosarcoma, and angiosarcoma. The tumor responses appeared to be similar to those seen with standard chemotherapy. In addition, the combination of these two drugs was found to be very safe and tolerable. The findings were published in January 2018 in the journal Lancet Oncology. They support future studies of this drug combination for people with specific metastatic subtypes. We are continuing to focus on identifying sarcoma biomarkers that allow us to predict who will respond well to this type of immunotherapy.

Sarcoma expert Ping Chi meets with research technician Makhzuna Khudoynazarova
Soft Tissue Sarcoma Clinical Trials and Research
Our doctors and researchers are constantly seeking new and improved treatments for soft tissue sarcoma through our program of clinical trials.
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We’re also exploring therapies that combine checkpoint inhibitors with new drugs that boost the immune response in other ways. For example, there is an ongoing effort combining nivolumab with NKTR-214. This drug is a modified form of a protein called interleukin-2, which is made by the immune system. NKTR-214 is designed to trigger other cells in the immune system to attack cancer cells. The goal is to see if this combination will increase the likelihood of an immune response for metastatic or locally advanced sarcoma.

In addition, there’s an upcoming study combining pembrolizumab with a drug called epacadostat that will be conducted in collaboration with medical oncologist Ciara Kelly. Tumors often can produce an enzyme called IDO1 to avoid the immune system. Epacadostat blocks this enzyme to help the immune system hit the tumor with its full force.

Most recently, in collaboration with Dr. Kelly, we conducted a clinical trial utilizing TVEC, an attenuated herpes virus injected directly into the sarcoma tumor, in combination with pembrolizumab. This trial just completed patient accrual, and we are currently analyzing the results.

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What about the use of adoptive T cell therapy for sarcoma?

We have been collaborating with a company to engineer T cells to fight synovial sarcoma. This type of sarcoma has a specific protein called NY-ESO-1 that is not on other cells. Because of that we are able to target the cancer cells selectively. The treatment is being tested in a pilot study at MSK. The trial involves removing T cells from a person with synovial sarcoma, engineering the cells to recognize the NY-ESO-1 protein, and then giving them back to the person in large numbers.

VIDEO | 00:31
Learn five reasons why joining a clinical trial at MSK might be right for you.
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As of November 2017, 37 patients have received these modified T cells in multiple groups with variations to the treatment approach. Overall, the response rate has been promising. There are ongoing efforts to optimize this treatment approach and determine the best strategy moving forward. We are now in the process of leading a similar effort for people with myxoid liposarcoma. Their tumors also express NY-ESO-1. This trial is actively enrolling patients.

Beyond this specific approach, we are working with MSK investigator Michel Sadelain on a type of adoptive T cell therapy called chimeric antigen receptor (CAR) T cell therapy. CAR T has demonstrated remarkable results in people with chemotherapy-resistant leukemia. We are trying to develop CAR T cells that will target a protein that’s on the surface of many sarcomas. That’s a big project that we’ve been working on for several years. We hope to launch a clinical trial testing this approach in the near future.

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What is the biggest challenge for using immunotherapy against sarcoma?

The major hurdle is identifying the right strategies for specific subtypes. It’s difficult to know what will work in a particular sarcoma. The cells all look different under a microscope and have different mutations. There are ongoing efforts to identify sarcoma biomarkers that can help us predict whether a therapy will be effective.

The important point is that there is great potential and hope for immunotherapy to have some effectiveness against sarcoma. Both checkpoint inhibitors and CAR T cell therapy have demonstrated success in other cancer types. We hope to continue to figure out ways to extend this benefit to people with sarcoma.

 

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Comments

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Hello-
Is there any clinical trial to test immunotherapy in patients with leiomyosarcoma metastatic happening there at this time?

Thanks

Dear Jason, we have a number of trials for different types of sarcoma that are looking at an immunotherapy approach. Some of these could include people with leiomyosarcoma.

To arrange a consultation to learn more, 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.

I was diagnosed with Myxoid Liposarcoma in mid 2013 and had a resection of tumor in my thigh. Unfortunately I have had three recurrences and my chemotherapy options are now exhausted. Is there any trials available for my type of liposarcoma?

Dear Sarah, we’re very sorry to hear that your cancer came back after treatment. We have a number of clinical trials for different subtypes of sarcoma at MSK. If you would like to make an appointment 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.

Hi,
My uncle has been dignosed with dedifferentiated retroperitoneal liposarcoma in May 2016.
He is 43 years and has had two surgeries since then. The beast is back again. he has four cycles of chemo with Erubulin but the scans show the tumors have continued to grow
He is now being treated with Olaratumab (Lartruvo®) + Doxorubicin
He is based in LA and being treated at ULCA. Are there any clincial trials available for him

Kind Regards
Ashrita

Dear,
do you use immunotherapy to treat ewing sarcoma and how much it costs?

Sara, thank you for reaching out. There are currently no trials at MSK using immunotherapy for Ewing sarcoma.

Here is a list of trials testing immunotherapy for Ewing sarcoma that can be found on the government’s web site Clinicaltrials.gov:

https://clinicaltrials.gov/ct2/results?cond=Ewing+Sarcoma&term=immunoth…

You also can learn more about Ewing sarcoma treatment at MSK here:

https://www.mskcc.org/cancer-care/types/soft-tissue-sarcoma/treatment-01

I was diagnosed with carcinosarcoma in 2015, had hysterectomy (full); chemo; recurred 1 yr later on vaginal cuff and had external radiation, did not dissolve complete tumor; more surgery, it to "scoop out what was left; residue left and small tumor so next was internal radiation;
recurred approx 4 months Metastasized to lungs!!! Treatments Anastrozole 1 mg daily; (#1 week Carboplatin and Gemzar (reduced because of Low white blood cells and again because of shingles; #2 week Gemzar: Last pet scan showed some shrinking of tumors and small tumors - Chemo again, same as last treatments (4 treatments-2 to go) thus far, but now having congestion, discomfort, coughing (nothing coming up)). Do you have any treatments for this??? Female age 74 in July.

My mother, 85 years old, has been diagnosed as liposarcoma April, 2018. No treatment option has been offered. Would it be possible to add her into your clinical trials for Immunotherapy? Thanks!

I was diagnosed with high grade myxofibrosarcoma in Feb 2018; I had two surgeries and 30 radiation therapy in my upper arm. As far as I know myxofibrosarcoma is not sensible to chemotherapy. I am glad to know some progress has been made in immunotherapy treating myxofibrosarcoma in Memorial Sloan Kettering. Is there immunotherapy trials/treatment available for my type of myxofibrosarcoma?

Hi,

I was diagnosed with desmoplastic small round cell tumor with metastasis to lung, liver, omentum and bones. I have tried the combination of opdivo and yervoy but it didn't work. There has been a recent relapse and am put back to chemo with docetaxel and gemcitabine. I'm wondering if there is any other method of immunotherapy maybe available to me through clinical trials.

What current therapies or immunotherapy treatment are available for synovial Sarcoma Stage 4? What options are available for patients who do not have the HLA-2. Can you still be qualified for the trails?

Dear Ralph, to find a list of sarcoma trials at MSK, you can go to https://www.mskcc.org/cancer-care/clinical-trials/search?keys=&disease=…. To speak with someone about which trials you may be eligible for, 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.

Any trials available for metastatic Ewing’s Sarcoma (both soft tissue and bone)?

Dear Rosanne, to see a list of our clinical trials for Ewing sarcoma, you can go here: https://www.mskcc.org/cancer-care/clinical-trials/search?keys=ewing&dis…

If you are interested in making an appointment for a consultation at MSK, 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.

Is there an approved, effective treatment for metastatic pleomorphic liposarcoma?

Shortly information about patient: My father has pleomorphic liposarcoma and the same time has metatastic bone tumor and liver tumor. Firstly, our onchology doctor used standart cheomotherapty treatment (adjuvan) for my dad. but in the first cure of chemotherapy, my dad had a heart attack. As a result of heart attack, my father had a stent operation and he is using blood thinner medicine (corasprine).

Dear Dilara, we’re sorry to hear about your father’s cancer diagnosis and other health problems. If he would like to come to MSK for a consultation about what treatments may be available to him, the number to call is 800-525-2225. You can 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.

Our son has been fighting an undifferentiated spindle cell sarcoma for 5 years. his cancer has metastasized to his lungs and c2 spine area. We are looking for immunotherapy options for him. Does MSK have any options that might be available for him?

My mother has been diagnosed with Sarcoma but unfortunately they are not sure which type. They thought it was melanoma however she is of african decent and the doctor said it was rare. She has a 12cm tumor under her left armpit. She had an MRI done and it shows it has metastised to her lungs (2cm). I just came across the website as she has refused vehemently to try chemotherapy. What is the duration of immunotherapy? Although it is a trial, are there any cost associated to it as i would love for her to commence immunotherapy treatment as soon as possible.

Dear Kay, we are sorry to hear about your mother’s diagnosis. If she would like to come to MSK for treatment, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Once she comes for her appointment, the doctors will be able to answer your questions. If she is not able to come to MSK but you would like to send her tissue slides to an MSK pathologist for more information on what type of sarcoma she has, you can go to https://www.mskcc.org/referring-physicians/pathology-consultations for more information on how to do that. Thank you for your comment, and best wishes to you and your mother.

My brother has angio-sarcoma which started on his head. It has now metastasized to his entire skull, lungs, lymph nodes and liver. He will be starting keytruda on Tuesday as a last ditch effort to fight this evil disease. Drs at John Hopkins have suggested strongly to contact hospice as this immunotherapy is the last treatment to try. Are there any other suggestions that you might have for him. He is only 65 yoa.

Dear Janet, we’re very sorry to hear about your brother’s diagnosis. If he is interested in coming to MSK to learn about other potential options, including the possibility of a molecularly targeted therapy based on the genetic changes in his cancer, 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 both of you.

my son was diagnosed with orbital rhabdomyosarcoma 3 year ago. He was treated with chemotherapy and radiation after biopsy. By the Grace of God he is fine now. I have read about the cases of re occurrence. I want to know what all new treatments are available for unfortunate cases of recurrent orbital rhabdomyosarcoma. thanks. rana shahid riaz pakistan

Dear Rana, we are sorry to hear about your son’s diagnosis but glad to hear he’s doing well. This is an active area of research at MSK and we are looking at new treatments in clinical trials. Thank you for your comment and best wishes to you and your son.

My daughter was diagnosed with a sarcoma called PNET in the cervical. He underwent surgery for removal of the tumor and subsequently chemotherapy euroewing 99. He remained in remission for 1 year 3 months and relapsed in the same place and pulmonary metastase. He did several cycles of chemo with irinotecan, temodal, ice, cyclophosphamide, topotecan, etc ... but unfortunately no drug seems to have had the expected efficiency. At the moment she makes protocol with gemcitabine and docetaxel, but it does not have much effect, besides that the docetaxel caused purple stain by the body, typical of allergic reaction. I wonder if there is any protocol under study for this type of sarcoma, because we no longer know what to do. The doctor suggested Pembrolizumabe, in a last attempt to get some efficiency. The days go by and I am distressed wanting a solution to my daughter's problem and praying that scientists will find something promising for her case. Thank you very much!

Luiz Roberto

My husband was diagnosed with Angiosarcoma of the lung in November ‘18. He is receiving Taxol. He has had 3 treatments. Would it be possible for him to receive Immunotherapy? And what is the prognosis for lung angiosarcoma? It is contained in his lungs. Thank you.

Dear Nancy, we’re sorry to hear about your husband’s diagnosis. Only a doctor who is familiar with his medical history would be able to tell you whether this therapy would be appropriate. We recommend you discuss this with his doctor. If he is interested in coming to MSK for a consultation with one of our doctors, the number to call is 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 and best wishes to you both.

My friend was diagnosed with spindle cell tumor in his mouth 13 years ago. He had surgery, chemo and radiation. Recently he was diagnosed with osteoradionecrosis and a fractured jaw. The bone deterioration was also an infection so he underwent hyperbaric treatment prior to surgery to replace the jaw. While healing from that surgery another tumor was found and immunotherapy was started.
The tumor has grown since then and MDs are discussing next steps. Do you have any advice? Are there any trials going on at MSK or at a hospital near Rancho Cucamonga in California?

Dear Cie, we’re very sorry to hear about your friend’s diagnosis. If he is interested in coming to MSK for a consultation, he can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information. If he is not able to come to New York City, another option would be to go to www.clinicaltrials.gov to look for trials that are closer to where lives. He might also want to refer to the list of the National Cancer Institute’s designated cancer centers to find a center nearby. The list is here: https://www.cancer.gov/research/nci-role/cancer-centers

Thank you for your comment and best wishes to you and your friend.

My father was operated twice to remove Chondrosarcoma grade III close to his chest. Radiation was done after 2nd surgery. Now there are small lesions showing metastasis to the lungs. I have the following questions:
(1) Is there an immunotherapy study effective for the chondrosarcoma?
(2) For targeted therapy, is the tumor gene reading a pre-requisite? That means that the biopsy or surgery to remove the tumor happens first before coming up with a targeted therapy?
(3) Is there any program for international patients? In order to make an appointment, is the physical presence of the patient required?
Thank you.

My husband has had metastatic alveolar soft part sarcoma. His metastasized lesions were removed from the brain and lung, 10 months ago. From six months back he has been on sunitinib. Is there any other option available or how long will he have to go on with the sunitinib. His scans as of now are clear.

Dear Sujata, we’re sorry to hear about your husband’s diagnosis but glad to hear his scans are now clear. If he is interested in speaking with someone at MSK about what other treatment options may be available to him, he can call 800-525-2225. You can go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment and best wishes to both of you.

Hello, i was diagnosed with myxoid leiomyosarcoma. Are there any trials I could join? Thanks

We’re very sorry to hear about your diagnosis. If you are interested in learning about sarcoma trials at MSK, you can make an appointment online or call 800-525-2225 to learn more. Thank you for your comment and best wishes to you.

I am 33 and I was diagnosed with embryonal rhabdomyosarcoma a month ago. The tumor was on my right wrist area. It has been removed with negative margins and they are recommending Chemotherapy (standard VAC). All studies of the benefits of chemo on patients have been done on PEDS (since it is mostly a PEDS disease) and not very many for adults. A second opinion doctor told me that it is hard to advise chemo to adult patients because the benefits have not be studied (or proven much more beneficial) and it would be a hard choice to make to proceed with chemo. My question is this, do you guys have clinical trails that do not involve chemo (like immunotherapy) for ERMS? I have noticed many trials requirements are only if chemo hasn't worked yet. Are there trials for alternative treatments instead (instead of chemo)? Let me know.

Dear Luis, we’re very sorry to hear about your diagnosis. If you’d like to consult with a sarcoma expert at MSK about treatment options, you can make an appointment online or call 800-525-2225. If you are not able to travel to New York City, we recommend that you seek out another consultation at an academic medical center. You might find it useful to consult the National Cancer Institute’s list of designated cancer centers. Thank you for your comment and best wishes to you.

Hi. My mother in law, 75, was diagnosed with retroperitoneal epithelioid sarcoma (about 10 cm touching but apparently not yet affecting stomach and pancreas).
She lives in Italy. Is there any chance immunotherapy could help her? Could she get the drugs and be treated in her country?

Dear Marco, we’re very sorry to hear about your mother’s diagnosis. We recommend that she discuss the possibility of immunotherapy treatments with her doctor. Whether she might benefit from these drugs depends on a number of factors. If she would like to arrange to have her records reviewed by a doctor at MSK, you can contact our International Center to learn about this.

You may also wish to go to www.clinicaltrials.gov to find out whether there are any clinical trials in Italy for her type of sarcoma. Thank you for your comment and best wishes to both of you.

Hello do you know of any immunotherapy treatments available for pediatric Ewing Sarcoma patients that do not involve chemo or radiation? My son is 16 and has been recently diagnosed with relapsed metastatic ewings Sarcoma. He underwent the typical protocol chemo treatment last year and had a distal femur/ knee replacement. Tumor tissue was 100% dead at removal, and all scans including bone marrow biopsies came back clean. Last treatment was in first week Dec. Clean scans end of Dec. Pain in hip on Feb, pet scan shows uptake in both ribs and right hip (tumor and surgery was performed in left femur so uptake is in opposite leg now). Confirmed he does have two small soft tissue masses in both ribs (assumed to be in bone since they are so close to bone), and small tumor in greater trochanter area in right hip. Caught this very early so biggest mass is size of pea. Would like to have him treated but not with chemo as he received the harshest chemo and doses for his cancer last year and it did not work, it only tore his body down and made him sick. Not interested in radiation as it may help with pain and managing tumor but will not kill it. Looking into Vigil study but it includes chemo. Really would like alternative treatments that do not involve chemo. Know there are other treatments used around the world to treat cancer including sarcomas without using chemo, would like to know if there is anything in the US specifically for minors. Thanks!

Dear Dawn, we’re very sorry to hear about your son’s diagnosis. If you would like to bring him to MSK for a consultation to learn about potential treatments for him, you can call 833-MSK-KIDS. You can learn more about pediatric care on our website. Thank you for your comment and best wishes to you and your son.

I need your expert advice and guidance in my son osteosarcoma treatment. 

My son, Krishna , 20 year old was diagnosed with osteosarcoma left femur in 2014, when he was 16.  1st line chemo with adriamycin+cisplatin followed by limb sparing surgery.

In 2017 recurrence at lungs, metastectomy done@ right lower lobe

In 2017 Nov, recurrence at lungs, metastectomy performed @ right lower lobe followed by 2nd line chemo, with HDMTX and GEM+DOCE protocol till April 2018.

In 2018 dec, recurrence at lungs, metastectomy performed @ right lower lobe.

Right now undergoing 3rd line chemo with IFOS+ETOP protocol. With the help of some good friends, I was able to contact NIH/NIC, Dr.Nita... she has adviced MIFAMURTIDE (MEPACT). This drug not available in India. I am able to import the drug from Turkey. Krishna is getting treated with MIFAMURTIDE along with IFOS.

I always believed in God and doctors like you who are kind hearted and guided me till this point in this long journey.  

I would be greatful if you can advise any other treatment / clinical trials which gives me hope.

thnx