Hi Rene,
My husband was diagnosed with Myxofibrosarcoma six months ago and is current under chemotherapy (Doxo/Ifosfamide/Mesna). Although the tumor has not increased in size but the chemo has failed to shrunk it. We are looking into what options are out there and I found that there was a report that 30% of patients with this type of cancer has expression for NY-ESO1. The pathology dept at MSKCC do not do this type of staining and sends them out to NIH. I was wondering if there is a way to get the tumor slides tested for NY-ESO1 expression.
The doctor here is pretty negative about the T cells adoptive transfer therapy, and says my husband cannot enter clinical trial for this type therapy because its only for synovial and other types not myxofibrosarcoma. I think its worth to know if it has NY-ESO1 expression so that it can open another option in the future. Do you know anyone or any companies that can help us. Any advise will be greatly appreciated.
1) NY-ESO-1 testing
NY-ESO-1 testing is usually done in the context of clinical trials. I had gotten the NY-ESO-1 test done in the context of the single patient protocol clinical trial. If there is a suitable NY-ESO-1 trial (peptide vaccine, adoptive T cell), your husband can be tested in that context, and it should be covered under the clinical trial.
I had my tumor tested over 8 years ago by Caris MPI (http://www.carislifesciences.com). They did test for expression of certain genes, but they did not test for NY-ESO-1. You can inquire to see if they check for NY-ESO-1 expression.
2) Getting into a NY-ESO-1 trial
I would recommend contacting Cancer Research Institute's clinical trial finder to see if there are any NY-ESO-1 or checkpoint blockade trials open for your husband. They have people that help you look for trials.
Even if some NY-ESO-1 trials do not list myxofibrosarcoma as an indication, it is worthwhile to call each site that offers the trial to ask if your husband qualifies. We know of many patients who were put into trials that did not specifically list their type of cancer. There are leeways.
3) Is radiation or cryoablation possible to one or several of his tumors?
This would generate a whole assortment of antigens, hopefully leading to a larger range of T cells that can recognize his tumors. One problem with a single antigen vaccine or adoptive T cell therapy is the possibility that the tumor eventually loses the antigen, leading to immune escape (parallel situation with antibiotic resistance). The possibility of this is decreased with treatments that generate T cells against multiple antigens.
4) Has your husband tried or considered PD1?
In some cases, the patient already has T cells against his/her cancer, but the tumor has defenses against the immune system. In that case, the treatment with PD1 can lead to the tumor shrinking/ disappearing. This can be gotten off-label if your oncologist is not willing to prescribe. Sometimes PD1 monotherapy results are not spectacular, so it's important to try to maximize the effect of the PD1 if you're going through all the trouble of getting it (see Chapter 16, section "A Tail of Survival")
Thank you so much for the info. I will ask the company, if they also look at NY-ESO1 and if they do immunohistochemistry. Due to the location at of the tumor being right next to the carotid artery, i think cryoablation would not be a feasible option but i think radiation would be possible. Is there any type of radiation you would recommend? Do you think IMRT or photon would also be good? Right now we are waiting for the clinical trial for TORC1 and 2 inhibitors to open. After that we are thinking of doing radiation then immunotherapy. Do you think doing adoptive T cell transfer then PD1 treatment would be a better strategy than the other way round? Sorry for asking so many questions. Looking forward to hearing from you.
If a trusted cryo doc (like Dr. Littrup) say it's unfeasible, radiation is certain non-invasive and easy to get anywhere. Note: an MSKCC cryo doc said her infratemporal fossa/jaw tumor was too dangerous to cryo, but Peter Littrup was able to do it "easily." Technique and experience is key. So make sure you're asking experienced cryoablationists.
For cryo-immune activation, you just need to kill *some* tumor in theory. If the radoncs all say that curative radiation therapy (independent of immune effect) is impossible, then the question we'd weigh is radiation side effects, and the implications on QOL (quality of life), versus any potential immune-activating benefits. In contrast, if there is any reasonable, objective, data-supported chance that radiation may be curative, or can buy considerable life extension, we would go with the maximum dose, for which photon therapy may have advantage in theory.
Your questions are very good ones, but unfortunately there's not enough data to say whether T cells before PD1 or vice versa are better. When T cells work they can be massively powerful & fast-working. But they also have potential toxicity. Generally speaking PD-1 is mild in comparison, even to many chemo or targeted agent regimens.
So in short, radiation + PD1 is a relatively easy-to-obtain option, with pretty good safety data and anecdotes of synergistic immune activation. Sometimes, timing is important and going with the logistically obtainable option may buy time to fight the next battle. Unfortunately, we've known many who succumbed waiting for that experimental therapy.
Here are some immunotherapy trials that Rene's oncologist highlighted. In addition, he recommended any sarcoma patient who wants to get into immunotherapy trials to see Dr. Conley or Dr. Somiaiah (links on the doctors below).
Immunotherapy trial: combination anti-PDL1 and anti-CTLA4 (Medimmune sponsored)
Status: 40 patients enrolled, and there’s a waitlist
Doctors:
Somiaiah (sarcoma) http://faculty.mdanderson.org/Neeta_Somaiah/
Conley (sarcoma) http://faculty.mdanderson.org/Anthony_Conley/
Subbiah (Phase I trial department at MD Anderson) http://faculty.mdanderson.org/Vivek_Subbiah/
Immunotherapy trial: NY-ESO-1 adoptive T cell therapy (Adaptimmune sponsored)
Cancer type: NY-ESO-1 expressing sarcomas (synovial sarcoma, myxoid liposarcoma) that are also HLA-A2
Clinical trial info: https://www.mdanderson.org/patients-family/diagnosis-treatment/clinical-...
Doctor: Araujo http://faculty.mdanderson.org/Dejka_(Steinert)Araujo/
Immunotherapy trial: intratumoral injection of TLR agonist IMO-2125 (developed by Idera)
with anti-PD1 or anti-CTLA4
Cancer type: Metastatic Melanoma (but Sarcomas may be included as well)
Clinical trial info:
https://clinicaltrials.gov/ct2/show/NCT02644967
http://www.iderapharma.com/wp-content/uploads/2016/11/IMO-2125-An-Invest...
Doctor: Diab http://faculty.mdanderson.org/Adi_Diab/Default.asp?SNID=0
Immunotherapy trial: systemic infusion of NKTR-214 (CD122 agonist that activates T cells +NK cells) (developed by Nektar) - altered IL2
Cancer type: Locally advanced or metastatic solid tumors
Clinical trial info: https://clinicaltrials.gov/ct2/show/NCT02869295
Doctor: Diab http://faculty.mdanderson.org/Adi_Diab/Default.asp?SNID=0
Conley (sarcoma) http://faculty.mdanderson.org/Anthony_Conley/