Elisa on Pembrolizumab / Keytruda

[Johannes]

Dear all,

Elisa and I have been wanting to write an update for a long time, but I guess we have been busy with things unrelated to her health (which is a good sign but not a good excuse for our silence!).

Elisa has been on Pembrolizumab/Keytruda since September and is still receiving it every three weeks. The first scan after a bit more than two months showed pretty much stable disease. We then decided to add radiation to the primary in the thigh, which Elisa received in five fractions (I believe it was 6.5 or 7 gy each). The subsequent CT scan showed remarkable shrinkage, both of the primary and of numerous lesions in the lungs. For instance, one 4cm-met shrunk to 3cm, and one 2cm met disappeared. On the last scan, a few more mets shrunk or disappeared, although two smaller ones grew a bit, so it’s unfortunately not all perfect. What is also interesting is that the radiologist did not speak of one big mass in the thigh anymore but of several smaller lesions, which sounds like a significant improvement. Side effects have been absolutely negligible, and Elisa is doing much better than last year.

So overall, it seems that the PD-1/PD-L1 checkpoint inhibitors are really a good option. A single agent might not be enough (that’s also what we were told by the PI of the Keytruda+Axitinib combination trial in Miami, which we were considering). But the combination of one PD-1/PD-L1 inhibitor and radiotherapy looks very promising and can apparently produce the famous abscopal effect.

With my very best wishes,
Johannes

[D.ap]

Johannes
What wonderful news!!
You both deserve a break however thank you for letting us know !
It made my day brighter as I'm sure yours and Elisa's day is
as well.
Love
The Pearson's

[arojussi]

If some mets grow and some shrink I personally believe that makes pseudoprogression more likely. If some mets grow and other just are stable, then real progression is more likely. Just my personal opinion. It is very hard to differentiate progression from pseudoprogression based on 1 scan and future scans are usually needed to confirm situation.

[D.ap]

Johannes
This is an article I found back a ways that I believe talks of the possibity of a systemic response

http://www.cureasps.org/forum/viewtopic ... int#p10587

[Johannes]

Dear Debbie and Jussi,

Thanks so much for your responses.

Jussi, we are also hoping that the few larger mets are only pseudo-progression. But then it seemed more common to see pseudo-progression during the first month of treatment with a checkpoint inhibitor, and less so after 9 months or so. Anyway, we are not too nervous about these mets right now but will monitor them carefully.

Debbie, I have posted a few more articles on the combination of immunotherapy and radiotherapy that may be of interest (they are pretty recent, but I have not searched for updates in a few months now). The bottom line seems to be that this combination is very, very promising, but that we simply don't know yet when it is best to treat, at which doses, etc.

All the best,
Johannes

[jcs2007]

thanks for the update on your treatment with pembrolizumab and hopefully you will continue to have positive results!
We are looking at the Pembro/Axi trial in Miami too. Take Care

[D.ap]

Dear Debbie and Jussi,

Thanks so much for your responses.

Jussi, we are also hoping that the few larger mets are only pseudo-progression. But then it seemed more common to see pseudo-progression during the first month of treatment with a checkpoint inhibitor, and less so after 9 months or so. Anyway, we are not too nervous about these mets right now but will monitor them carefully.

Debbie, I have posted a few more articles on the combination of immunotherapy and radiotherapy that may be of interest (they are pretty recent, but I have not searched for updates in a few months now). The bottom line seems to be that this combination is very, very promising, but that we simply don't know yet when it is best to treat, at which doses, etc.

All the best,
Johannes

Hello Johannes and Elisa

Thank you so much for the links to read about.

How big is the primary at this time in Elisa's thigh?

The diagnosis was 7 years ago ?

http://www.cureasps.org/forum/viewtopic ... =884#p1856



The abscole effect you presented in your opening post is an interesting concept

https://en.m.wikipedia.org/wiki/Abscopal_effect

[D.ap]

http://www.cureasps.org/forum/download/file.php?id=115

Radiotherapy and Immunogenic Cell Death
. Author links open the author workspace.Encouse B.GoldenMD, PhD*. Numbers and letters correspond to the affiliation list. Click to expose these in author workspaceOpens the author workspaceOpens the author workspace. Author links open the author workspace.LionelApetohPhD†. Numbers and letters correspond to the affiliation list. Click to expose these in author workspace‡. Numbers and letters correspond to the affiliation list. Click to expose these in author workspace§. Numbers and letters correspond to the affiliation list. Click to expose these in author workspace
Show more

"Advances in understanding the mechanisms that underlie the interplay between radiation-invoked immune responses and tumor regression are underway. Emerging applications of local radiotherapy as an immunologic adjuvant have provided radiation oncologists with a method for converting malignant cells into endogenous anticancer vaccines. The dispersion of radiotherapy-induced immune-stimulating tumor antigens released from dying tumor cells into the surrounding milieu (known as immunogenic cell death, Fig. 1), is one such exploitable process that contributes to the propagation of antitumor immunity. Downstream components of the immune system may suppress, promote, or ambiguously affect antitumoral responses. Additionally, host, tumor, and treatment-related characteristics govern the significance of these signals, thereby dictating therapeutic outcomes. Herein, we review the process of radiotherapy-induced immunogenic cell death and its role in generating an in situ vaccine to help refine radioimmunotherapy-based protocols."

http://www.sciencedirect.com/science/ar ... 9614000824

[D.ap]

Johannes

Within the first article I was reading that in prostrate cancer multiple verses 1 dose gave better results when used concuminiatly with immune thearpy , as well.

[Olga]

Hi, can you please post the clinical trial # and location? I am surprised they allowed the radiation to the primary while on a trial.

[Johannes]

Hi Olga,

It is an off label use of Keytruda, i.e. not a clinical trial, which is why radiation was possible.

Johannes

[Olga]

I'll move it from the trials to a systemic treatments forum
Board index Systemic Treatment Immune checkpoint inhibitors ICI (PD-1 and PD-L1 targeting drugs) Keytruda

[D.ap]

Hello Johannes
How is Elisa doing ?
Was researching MAGE A3 antigen .
My search on the forum brought me here .
:)

Love

[Johannes]

Dear all,

Sorry for not updating the forum for a little while. Here is a summary of what has happened since I last posted in November 2017:

In early 2018, so after a bit more than 12 months on Keytruda, there seemed to be a bit of progression in the lungs. We therefore thought that adding another drug would be a good idea and managed to get off-label/compassionate access to Axitinib/Inlyta (so the same combination as the trial in Miami). Elisa tolerated Inlyta very well, but unfortunately she could try this combination only for a few months, because Merck decided that Keytruda would not be provided on a compassionate basis for longer than a total of two years. Therefore, both treatments were stopped in October 2018.

The great news is that Elisa did have a good response to this combination treatment: the last CT scan in December showed again a bit of shrinkage when compared to the one done in October. The other good news is that if there is progression, she should be able to receive Keytruda at her regular hospital (to reduce the cost, probably only every six weeks though).

We really think that initially the combination of radiation and Keytruda was beneficial, and that eventually adding Inlyta to the Keytruda treatment was also a good idea. By the way, the primary tumour in the thigh, which used to be very large (up to 25cm long etc.), has dissolved to one subcutaneous lesion of around 3x4cm and a few smaller ones. It’s hard to know what exactly incited this response in the thigh as she also got radiotherapy. The surgeon, however, still does not recommend resecting these remaining lesions, since they are too diffuse (and probably also because she has metastases…).

So, overall, things are well. We would have preferred if Elisa could have continued the Keytruda+Inlyta treatment for a bit longer, but perhaps at least Keytruda is still doing its work. As we know, there are sometimes ongoing responses with immunotherapy even several months post-treatment.

All the best,
Johannes

[Olga]

Thank you for the detailed update. It looks like the response to Keytruda is ongoing after the drug stopped. Which is not rare as this is consistent with the mode of action of the drug - to help to the immune system to discover the tumor by removing the brakes, and to create the tumor specific immune cells killers, with the memory for the specific tumor.
Re. situation that In early 2018 (after a bit more than 12 months on Keytruda) there seemed to be a bit of progression in the lungs. Was the progression seen in some or even one met? We have already found out from the posts of our other patients on ICI drugs, that sometimes there are immune escaped mutated cells in one or few mets, lugs are often mentioned. In some cases treating the single or few recurrent mets by the cryo or the radiosurgery solves the problem at least for some time. Our collective experience in this area is limited for now as this is all very new.
The other thing is re. primary remains. On one hand I would be saying to remove it as the tumors produce an immune suppressive effect but on the other hand the massive surgery would produce the very immune suppressive effect as well and with the immune system at work it is hard to say what is less harmful. May be it is better not to interfere with the ongoing response for now.
There are quite a few additional drugs are in clinical trials for the cases when there is no response/lost response to ICI drugs. Some of them are injected into the tumor with the ICI drug restarted, to trigger the response again. In some clinical trials 20% of the people had the excellent response to that strategy and Elisa would be an ideal candidate with her primary tumor easily accessible. In some studies simply restarting the ICI drug after the interruption period gives the good result as well, especially if the patient was responding before and the drug was stopped by some reasons - two years run out, side effects etc.