Elisa on Pembrolizumab / Keytruda

[Johannes]

Dear Olga,

Thanks for your quick response!

We went again through the CT reports of the lungs, and although they are not always as detailed as we would like them to be, it appears that indeed only one lesion clearly progressed (from about 1x1cm in September 2017 to 1.6x1cm in July 2018). All the other lesions seem to have remained stable, or were noted as being only 1 or 2mm larger at some point (but not on each scan, i.e. they did not grow 1 or 2mm every few months).

By the way, some of the lesions were noted as being "centrally necrotic" on the past report in December. We are not entirely sure, but we have decided that we would treat that as a good sign!

What I also forgot to mention is that Elisa went through a brief but quite scary episode around Christmas: she suddenly coughed up quite a bit of blood, including several clots. That happened 48 hours after a long flight, so we (and the doctor at the emergency) first suspected a pulmonary embolism. But that was ruled out thanks to a CT scan, and the radiologist hypothesized (question marks included!) that she might have coughed up some necrotic tumor tissue…

All the best,
Johannes

[D.ap]

Johannes and Elisa
I sit here and read all you report with smiles and admiration as you’ve both been thru a lot .

I’m looking at all you’ve seen and experienced and wish you continued success .

If I may ask for a synopsis of your dx’d to current journey when you get a moment ? From 2010 dx’d to current ?

I see pazopanib , MDM2-antagonist , Keytruda axitinib , radiation to the primary ? Lung tumor treatment ?
Were you all ever part of the MAGE A3 antigen trial and tested ?
My love to you both.

[Bonni Hess]

Dear Johannes, It is so good to hear from you and especially good to hear the very good and encouraging news of dear Elisa's very successful response to her combination Keytruda and Inlyta (Axitinib) treatment with lung met shrinkage, stabilization of her disease, and the dramatic shrinkage of her very large primary tumor. The new Immune Checkpoint Inhibitors like Keytruda, Opdivo, and Tecentriq certainly seem to be showing great promise for ASPS patients especially when used in combination with other drugs like Axitinib, or when used simultaneously with radiotherapy to create the abscopal effect. It is very encouraging to know that the drug appears to continue to be effective for a prolonged amount of time even after the treatment is discontinued as has been the case with Auston Ward from Toronto. Thank you so much for sharing this very good news and the extremely important information regarding Elisa's very successful Keytruda response which provides great Hope for everyone in our ASPS Community. Please know how very happy I am for Elisa and you, feel the embrace of my happy hugs, and keep in touch as you are able---you have been missed!! Sharing the great joy of dear Elisa's treatmenr success with much happiness, special caring, and continued Hope, Bonni

[Johannes]

Dear all,

Here is another update about Elisa!

The short story is that she is again on Pembro & Axitinib and doing relatively well.

She had been off all treatments for almost a year (since October 2018) when some of the lesions started to slowly grow again. We were thinking about what to do when she had a branch retinal artery occlusion in September 2019. Because of that, she lost part of her vision in one eye. This is an indeed extremely rare complication, and we still don’t know for sure what caused it. It could have been a micro fracture in the femur that created a fat embolus; it could also have been a very small tumor tissue that got stuck in the eye… As part of the investigations to try to find the cause of the occlusion, a heart echo (then confirmed by an MRI) showed a heart met (about 2cm). This was new to us, but when the new images were compared to older CT scans, the met had been around for at least two years (it had just not been picked up).

At one point at the emergency, she suddenly started to cough up quite a lot of blood. Fortunately, the bleeding stopped by itself, but another series of scans showed that all the three bigger lung lesions had decided to grow quite quickly… So she resumed Pembro and received radiation to these three lung mets and also to the bone lesion in the femur in October; Axitinib was added in November. The scans in December and March showed good response to these combined treatments in the lung mets; they all shrunk by about 1cm (including one lung met that had never responded to the previous round of immunotherapy from 2016-2018!). The biggest one is now down to 25x25mm. Unfortunately, the hole in the femur and what is left of the primary in the thigh is still about as big as before, which is a bit disappointing, but we hope that these lesions simply need a bit more time to respond. The heart met is also stable.

Elisa is tolerating the treatments very well; she is also a lot fitter than only a couple of months ago and has significantly less pain in the thigh.

Obviously it would be difficult to say what exactly worked this time. But I guess it’s reasonable to say, it should be good to know, that immunotherapy (perhaps when combined with radiation) can work again after a break – in Elisa’s case after 12 months.

With my best wishes,
Johannes

P.S. I will post a few interesting articles in the publication section.

[D.ap]

Johannes and Elisa
Truly happy Elisa is getting better with the number 2 round? Of Keytruda and axitinib .
If I might I’d like to link your journey to date.

viewtopic.php?p=1856#p1856

Looking forward to reading your medical posts .
Love

[Ivan]

I'm sorry to hear that you, like me, have a heart metastasis.

However, I am glad to hear that you were able to successfully stop and restart PD-1 :)

1) Eat lots of fiber
2) Take vitamin D
3) Get lots of sleep
4) Do cardio
5) Lift some weights to gain muscle

If that can all be done, I bet you're gonna have a great result :)

[Johannes]

Thanks for your tips, Ivan!

Re 1) Trying our best - as vegetarians, we eat lots of legumes, vegetables, whole grains, nuts, seeds, etc!
Re 2) 1000 IU per day.
Re 3) Aware of the importance of lots of sleep (and it usually works...).
Re 4) Aware of that importance too; with the leg being better, Elisa has, again, been more active recently.
Re 5) I guess I will have to try to convince her of the usefulness of bodybuilding though! ;)

Johannes

[Johannes]

Hi everyone,

Here is an update about Elisa’s continued experience with Pembro + Axitinib. She has been doing well overall, with basically no side effect, but the last scans unfortunately showed a mixed response.

The fairly good news is that the three lesions in the lungs are stable (or have perhaps slightly decreased in size again when compared to the scans 6 months ago). These three lesions were all irradiated in October 2019 and have significantly shrunk since then – they have never been that small!

Bad news: the heart met has grown, from around 39 x 24 x 28mm (in September 2019) to 50 x 28 x 30 mm. At least this has not affected the heart function, as confirmed by a cardiologist. The plan is to monitor the heart function with ultrasounds and the size of the met with MRIs.

Moreover, the two main masses in the thigh – one involving the femur, and a subcutaneous one –have also grown a bit. This did not really come as a surprise to us, as the subcutaneous has a lump sticking out at the surface of the skin, which makes it easy for us to monitor. This lump has actually oozed a bit several times over the past few weeks; it’s not dramatic, but obviously inconvenient. Since this mass is growing and could cause more problems, the orthopaedic surgeon (and sarcoma specialist) has said that he could remove it. Apparently this would not be a big surgery; he would have to make an incision of about 4cm in diameter at the surface, and cut a wedge of a depth of about 6cm. And although it’s difficult to tell for sure, this subcutaneous mass does not seem to be connected to the other mass deeper in the thigh, so he thinks – but won’t know for sure until he sees inside – he could avoid cutting through the tumor.

This surgery could be done in two or three weeks, but we are not yet sure if Elisa should go forward with it. The next Pembro treatment is
scheduled for this Friday and would probably have to be skipped.

It’s frustrating that the systemic treatments – for which we fought so much! – are not working as well as we hoped (at least not at the moment…). We both had a lot of stress unrelated to her disease in the past six months, which surely hasn’t helped.

All the best,
Johannes

[Olga]

Johannes,
Hi,
thank you for the update. The reason that we usually recommend to remove the bulky tumors before starting the immunotherapy is their ability to emit the immuno suppressive substances into the bloodstream and to interfere with the immune response elsewhere. This is the important fact to understand - there are NO innocent tumors in the body, period. Even if they are not life threatening, they are damaging for the body to have overall. It had to be removed a long time ago IMHO. The oncologists keep applying the general principals to metastatic ASPS patients that support the surgeries only when it is necessary or are urgently needed to improve the QOL. But in ASPS it should not be used as it is a slow growing sarcoma and simply removing/locally destroying growing mets - mutations escape artists - might improve the survival, it is proven and published. Especially if you understand the biology of ASPS and that its bulky tumors always have some areas of necrotic tissue inside so they start to rot as the time goes and it increases the inflammation in the body a lot. Which you do not want if the immunotherapy treatment is ongoing.
Go for the surgery, remove that ASAP - if there is an enthusiastic surgeon that is willing to do, it is a gift. The half life of the K is actually much longer than it was previously assumed in some patients might go 2-3 months. After the surgery, let it heal and restart K with adding the IMRT or some other radiosurgery treatment for the bone met - short intense course to the next K treatment - before or concurrently with it. With the goal to get the abscopal effect in the heart.
Elisa body will be happy to get rid from this oozing tumor that started to rot inside. Then you will see if there is a response to ICI restart in the heart.

[D.ap]

Johannes and Elisa ,

I’m sure sorry to hear of the heart met discovery .
What Olga is suggesting makes perfect sense to begin with with the surgery ,and Keytruda to follow in the distant future . Getting rid of the infected sebaceous cyst and aiding the immune system by ridding it of it, and then moving onto the femur involved with radiation and Keytruda , sounds like a good plan .
Hope today finds you all getting answers !

Ps how have you been counseled on the heart tumor .
Antibiotic wise?

Love ,

[Johannes]

Hi Olga,

Thanks so much for your prompt response and for sharing your opinion - very useful, as always.

Elisa underwent the surgery about 10 days ago; it became clearer and clearer that this subcutaneous mass had to come out. The surgery seems to have gone well. Although the incision was fairly large, no skin graft was needed, which was really good news. Elisa was able to walk with crutches almost right away. What has been scary and exasperating is very sharp pain behind the knee that first occurred a few days after the surgery. Elisa describes it as if something exploded inside a blood vessel, or an electric shock; it only lasts a few seconds, but it’s really intense. A Doppler that was done to rule out a thrombosis came back negative; so probably it’s ‘only’ neuropathic pain. Otherwise, she has had a lot of headache and a few severe episodes of migraine (perhaps a result of the anaesthesia?).

By the way, I would not describe the subcutaneous mass that was removed as the primary tumor. Initially, the primary tumor was not only much bigger but also a lot deeper in the thigh (i.e. inside the muscles, around the femur and the sciatic nerve). Fortunately, it shrunk significantly on several treatments, including Keytruda. The subcutaneous lesion slowly developed over the past few years, following a biopsy that was done to check Elisa’s eligibility for a trial… very stupid. Anyway, now there is only a relatively small mass left in the thigh (which unfortunately still involves the bone), to which the subcutaneous mass was apparently not connected.

All the best,
Johannes

[D.ap]

Hello Johannes ,
It’s good to hear of Elisa’s surgical removal of the subcutaneous tumor .

Have you all had an MRI to investigate the headache. ?
When was the last Keytruda infusion ?

I hope today finds Elisa recovering nicely.
Love,

[Johannes]

Hi,

Just a quick update to share the good news that the surgeon managed to remove the tumor with negative margins!

Otherwise, Elisa still tends to get more migraines than before the surgery (Debbie, to respond to your question: it's true that she has not had an MRI of the brain in a while, but the symptoms don't seem to be typical of brain mets). Fortunately, the past few days have been a lot better.

By the way, her last blood tests showed that the hemoglobin and ferritin levels were really down; as a woman at that age, she is obviously at risk of iron deficiency, but this still came as a surprise (perhaps this was caused or worsened by the surgery?). Anyway, she is eating even more consciously than before and has also started iron supplements, hoping that this will help.

Best wishes,
Johannes

[Olga]

Thank you for the update. Does Elisa get her blood checked frequently? See few of the blood test results side by side to figure out if there is seems to be any process ongoing, a tendency. This is how you can notice the autoimmune side effects developing before they are obvious. Ivan uses his access to the blood tests online that allows him to make graphs of the chosen variable to see the tendencies.
And get the brain MRI. The symptoms alone should be enough for the oncologist to order it. Plus start looking for the ablation dr to get evaluated if it is feasible to eliminate the remaining primary tumor involving the bone if it looks viable on the MRI scan, at some point in the future.

[Johannes]

Hi Olga,
Elisa usually has the blood tests every three weeks, which is why it was easy to figure out that there was actually a sudden drop of the hemoglobin levels.
She has already received a lot of radiation therapy to the thigh/femur, and it's pretty clear that more won't be possible. Or were you referring to another possibility of ablation?
Thanks!
Johannes