PD1-positivity and PD-L1 expression

[Johannes]

I hope everyone had a wonderful holiday! I am sorry that I haven't updated my post in a while. I just wanted to post a quick update to let everyone know that my 6 month scans in early December showed that my target tumors had shrunk another 14% for a total shrinkage of 56% since I started the study in June!! In additional, most of my larger lung nodules are now below one centimeter in size, except for two that are just over one centimeter. Many other lung nodules have disappeared completely!! This is super exciting because I had dozens of lung nodules over a centimeter and 5-6 over two centimeters when I started the study last June (I also had one close to 3 centimeter that was scaring the death out of me!!). It is just so nice to have hope for the first time in a long time!!

In other good news, I was able to get another ASPS patient the information needed to get into the same study as me and he has been on the protocol nearly two months now and will get his first scans in the next week or two. The drug company is watching our progress with interest and Dr. Hong says that if he also responds, that the drug company has indicated that they will open up a treatment arm just for ASPS patients!!! This is super exciting as I get messages all the time from other ASPS patients wanting to get into the study, but it is currently closed to any new partipants. There are several other studies with MEDI4736, however, and this drug seems to be the common factor in the immunotherapy success stories thus far. Anyway, I get my next scans at the beginning of February, and will update you on my progress, but let me know if you have any questions in the meantime.

Take care,

Rachel

Hi Rachel,

I hope your early February scan will also be positive! And thanks for posting all this very useful information about your response to MEDI4736 and Mogamulizumab.

As we were discussing the possibility for my partner Elisa to get into a PD-1 or PD-L1 trial, such as MEDI4736, one point that was raised by her oncologist was whether your tumor had been tested for MSI (micro-satellite instability). There seems to be a correlation, at least in certain tumors, between PD-1/PD-L1 and MSI, and MSI-high is required to get into some of these trials. Elisa's tumor was tested, and the result came back as MSI-low. So, do you know if your tumor has been tested for MSI?

Again, I hope that you continue to respond to this combination!

Thanks and all the best,
Johannes

[D.ap]

Johannes and Rachel
My love and good thoughts to you both.

I'm sorry to interupt, but what tumor was used for the testing and how was the test performed?
So Elisa was tested for PD units on the tumor as well as microsatellite instability?

Was the current tumor any where near in comparison to her primary pathology report?

Thanks in advance
Debbie

[Johannes]

Hi Debbie,

Thanks for this.

To clarify: they used an archived tissue from the lung biopsy that was done in 2009 and on which the diagnosis was based. This was only for MSI, not for PD-1 (or PD-L1) expression. We have a copy of the report, but I can't find it right now - sorry! What I remember is that 4 or 5 antibodies were used to determine whether the tumor is MSI-high or MSI-low.

MSI-high would have been needed to get into this Pembrolizumab trial: https://clinicaltrials.gov/ct2/show/NCT ... bec&rank=7 (one of the inclusion criteria "for any other advanced solid tumor" being that it is Microsatellite Instability (MSI)-High).

I hope this helps.

Best,
Johannes

[D.ap]

Thank you Johannes

It was very helpful.

I'd like to ask you and Elisa what your primary pathology said about the mitotic rates if you have that in your minds eye or near you .

Do you agree that mitotic rates might be equivalent to mutative and or mutatations as are seen with micro satellite lows and or highs later on with ASPS ?
I've linked you to an article on low levels cause of MSI

http://www.cureasps.org/forum/viewtopic ... 9004#p9004

Love
Debbie

[Johannes]

Hi again Debbie,

The primary pathology report does not seem to say anything about mitotic rates. What it does say is that "rare mitoses are seen". In case this helps, the report also says that "no necrosis is observed".

I am not too sure about the correlation between MSI status and mitotic rates, but I guess it makes sense to assume that MSI high implies or leads to high mitotic rates, and that a generally more "stable" tumor like ASPS can be expected to be MSI low and have low mitotic rates.

Best,
Johannes

[D.ap]

Johannes
Thanks so much for your response.
I am finding alot of low mitotic reports from different folks and have read that ASPS is typically low mitotically.

Joshua's pathology report was a 6/10 though so I am wondering if that changes from soft tissue then to organs or if a patients primary is deemed high with mitotic cancer cells, will they have faster dividing cells ?

And on another note can that be controlled by the PD drugs in the long run..
Maybe Rachel or other PD folks have an opinion.

Love and best to you as well..
Debbie

[rachelve]

To answer your questions, my tumor was not tested for MSI prior to my trial or at any other time. I believe my miotic rate was either 7/10 or 8/10 on my primary path report, but I would have to look it up to be sure. I am also unsure of the correlation between a high level of MSI in a tumor and a high mitioic rate.

With regard to my most recent scans, they show that my tumors are continuing to respond to the trial drugs and that my target tumors have now shrunk by a total of 65%!! So, I keep trucking along on the trial. The only downside is that I started getting nausea with my treatment in December (new symptom out of nowhere) and it has progressively gotten worse. I have lost a total of 25-30lbs since December because I am simply unable to eat due to the nausea. I am on a host of different anti-nausea meds, but none of them work very well. Last time it got this bad, I was on cabozantinib and I had to resort to marinol (which is the pharmaceutical version of thc). I may have to try and see if I can get it again if my nausea gets much worse, but I hate to take it if I can avoid it.

Anyway, that is the update on me. I hope all is well with everyone else!

Rachel

[D.ap]

My love to you , Rachel. Thank you from bottom of my mom heart.

You have access to dietician / nutritionist? An ND?

Will touch base in morn

Love
Debbie

[D.ap]

Good morning all
I've been looking at the pd1 write ups and some of the nauseas culprits
Rachel when was your last blood work performed and does your doctor have an opinion on the sudden sickness? Thyroid still ok. Liver?
Joshuas thyroid is back to normal after being low after 2 months on sutent.
Remind me have many infusions you've had? They are 2 times a month? 9 months now?
Also on the cometriq, does this sickness seem similar ?

I'm sorry to hear of the nausea.
Have you tried Zofran?
Josh took it along with his Temador dosage and had good results.

The link to your discussion and the quote-

http://www.cureasps.org/forum/viewtopic ... 1104#p8556

"Finally, I have been part of a clinical trial at MD Anderson since June 22nd taking a combination of MEDI4736 and Mogamulizumab. Today I got the results of my 4 month scans and learned that my tumors have shrunk a total of 48% overall. My side effects have included a rash and moderate fatigue, but overall, I have found the immunotherapy drugs to be very tolerable. "

Love
Debbie

PS was reading back on your post and the clip markers they left in your abdomen, did they get removed or did they dissolve?
Just curious

[D.ap]

Rachel

My love to you
Hope to hear of good scan results.
Hugs

[D.ap]

UCLA's Dr. Antoni Ribas Discusses PD1 and PD-L1 Targeted Cancer Drugs


https://m.youtube.com/watch?v=oew4OCA9Kp0

[D.ap]

Good morning Rachel

Just touching base to see how you are doing with treatment ?
I'm so hoping you are weathering meds without any more nausea and with great results !

Love
Debbie

[rachelve]

Sorry it's been a while since I checked in, but I have been pretty ill from side effects with the trial drugs. I continue to suffer from moderate to severe nausea around the clock despite multiple anti-nausea meds. I ended up being hospitalized twice in March for 9 days each (first at MD Anderson then two days later I was readmitted for another 9 days to my local hospital). They did two endoscopies (one at each hospital) and a brain MRI (to rule out tumors as a cause of the nausea since it is not responsive to meds). The brain MRI was clear, but the upper endoscopies showed severe gastritis. I was put on a burst course of steroids, which got the nausea under control enough so that I could go home. Once the burst steroid doses were done, I continued to have severe nausea, so I am now on a low dose steroid twice daily which helps more than any of the other anti nausea meds I've been on but I still feel pretty miserable most of the time.

In the meantime, I missed two courses of my study meds while I was in the hospital. In addition, my dosages had to be lowered because I have lost more than 10% of my body weight since starting the study (I've lost a total of 60 lbs). However, my most recent scans showed that the drugs continued to work while I was not taking them. There was some slight growth in a couple of nodules, but overall my target tumor burden has decreased by a total of 70% since I started the study at the end of June last year!!! This is fabulous news, so I plan to do the best I can to tolerate the nausea and hope it gets better soon.

[D.ap]

Rachel
My pc is updating soo.. On my small device
Phone
I am so sorry for your experiencing of continued nausea
Have you had a chance for an internal medicine Doctor to look over your current meds ? Including your PD Med ?

That sure can cause unlikely conflict in trying to regulate our bodies thru medicines and even with herbs etc
I will touch base a little later and write
It's truly good to hear your note today!

Sure hoping for u to feel better soon

Love
Debbie

[D.ap]

Rachel
Love to you today and always
Blood work good ?
I think maybe cultures like cultures to tell of digestive issues ? BM ?

As a forum we sure have experienced intestinal tumors , but as always very slow and not always detectable at their small size ?
Just closing thought ..

Keep an eye on the scopes and other indicators
Please run by doctors soon
Hugs girl : )
Night as full moon in Midwest