Meng from China-Dx 2008 (PD-1 therapy)

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Lisa
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Meng from China-Dx 2008 (PD-1 therapy)

Post by Lisa »

Hello everyone, I’m Lisa from China. I have posted my own treatment history in the forum already and thanks for all your suggestions!
Now I open this new topic to share the treatment of another Chinese patient who has been fighting with ASPS for more than 7 years. Recently, she had PD-1 therapy combined with Cediranib and received really amazing results. I will firstly briefly describe her treatments before using PD-1 treatment because I cannot wait to share the unbelievable results with you! :D

She was diagnosed in 2008 (Found diffuse mets in lungs but cannot find the primary tumor). In June 2012, the primary tumor (8*6 cm) was found in her left thigh and removed in August 2012.

Following are the treatments before using PD-1:
In June 2012, the largest nodule in lung was 2.5*1.9 cm
In September 2013, the largest nodule in lung was 3.2*2.6 cm
In May 2014, the largest nodule in lung was 3.8*3.4 cm. And then 3 tumors were treated by using Cryoablation
In June 2014, the largest nodule in lung was 3.4*3.2 cm
In July 2014, 2 mets (1.2*1 cm and 4mm) were found in brain MRI scan and treated by Gamma Knife. Had lung infusion chemotherapy--several mets shrunk by several millimeters after two courses of treatment.
In August 2014, continued lung infusion chemotherapy--result showed disease progression, so stopped therapy.
In November 2014, two nodules under abdominal wall and scalp were removed. A nodule sized 0.9*0.7 cm was found in liver.
In December 2014, started taking Pazopanib . At that time, the largest tumor in lung was 4*3.2 cm
In Jan 2015, the liver tumor shrunk to 0.9*0.5. In Mar 2015, the largest nodule in lung grew to 4*3.6 cm; the liver nodule shrunk to 0.3 cm
In April 2015, new 8 nodules were found in brain Mri scan and all of them were treated by Gamma Knife.

Following is the PD-1 therapy combined with Cediranib:
In June 2015, scan results show:
Brain: the largest tumor was 0.8*0.7cm
Liver: 0.3 cm nodule
Pancreas: a 0.7cm nodule
Lung: the largest tumor was 5.4*4.5 cm (1.4cm growth in 3 months)

In June 2015, started taking Cediranib. After taking 16 days, the largest lung tumor shrunk to 5*3.9 cm

In July 2015, she started PD-1 therapy combined with Cediranib. After 4 times PD-1 therapy, she stopped the treatment due to serious side effects.

In Sep 2015, scan results show:
Brain: the largest was 0.8*0.7 cm and possible new nodules
Lung: the largest was 6*4.8cm (this largest was a fusion of small tumors), the rest tumors grew about 2-3 mm.
Pancreas: several nodules were found, the largest was 2.2*2.5cm

In 25 Sep 2015, she continued Cediranib
In Oct 2015, two new brain mets (6.6*5.2*5.4mm; 5.7*4.9*4.8mm) were treated with Gamma Knife

From Oct 2015, her overall condition has became much better: she had been suffered from cough for more than 2 years, but from that time, she does not cough at all. Appetite and physical strength have been improved a lot; her weight has gained more than 5kg till now; the blood oxygen goes back to 97 (which was stable at 85, even lower than 80).

In Nov 2015, her latest scan results show following:
Lung: the largest tumor shrunk to 2.3*2.7cm, total number of mets reduced .
Pancreas: the largest tumor shrunk to 1.7*1.8
Brain: overall, mets shrunk. can see cavity in tumors.


The main side effects:
Aggravated cough, feel weak and exhausted, diarrhea, sensitivity in mouth. And the patient developed fungal infection by testing phlegm after 4th PD-1 therapy.

It is the unbelievable result! Before PD-1 therapy combined with Cedirinib, she had hundreds of mets in her lung and many of them were larger than 2cm. Recent CT scan shows the largest is 2.3*2.7cm, the number of mets reduced and most tumors are smaller than 1cm. It is noticeable that after 4 courses of PD-1 therapy, it showed a significant disease progression, especially in Pancreas mets. However, 1 month later, the patient felt much better physical condition that better than past 3 years. It seems that from that time, the lung tumors have shrunk significantly so that the patient stopped coughing.
Therefore, this amazing result should be attributed to the combination of PD-1 and Cediranib? Would Cediranib alone can achieve such significant results?
If this is partly because of PD-1, it seems that PD-1 therapy may result in pseudoprogression?
What should this patient do next? She has stopped PD-1 therapy for about 3 months and now taking Cedirinib only. Should she continue using PD-1 therapy or just taking Cedirinib to see the result in next scans?

I attach the pictures that are the comparison of two latest lung CT scan results. the picture on the left is the scan done Nov 2015; and the picture on the right is the scan done Sep 2015. Please feel the incredible changes in her lung!!!
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Lisa
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Re: Meng from China-Dx 2008 (PD-1 therapy)

Post by Lisa »

Sorry, I forgot to mention the dosage used in PD therapy.

PD-1: Keytruda
using reduced dose: 50mg each time and using once every 18 days

Cedirinib:
using 35mg everyday
Ivan
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Re: Meng from China-Dx 2008 (PD-1 therapy)

Post by Ivan »

It's amazing to see how much healthy weight she gained. It's clear even from the CT scan how underweight she was.
Olga
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Re: Meng from China-Dx 2008 (PD-1 therapy)

Post by Olga »

Lisa, thank you very much for the very detailed report about this patient's treatment history. Few interesting for me details were chemo therapy lungs infusion (it was done in Europe before - Dr.Shill as I remember - but I was not expecting anyone doing it outside of the clinical trial). The other thing was a treatment of that multiple brain mets by GammaKnife at once.
Re.Keytruda+cediranib combination and if we can figure out what is the active ingredient. I think we can not. Cediranib is a very active drug in ASPS. We have a patient in complete response with lung and pancreatic mets regression. Of interest she also had non-responding soft tissue mets that needed to be resected. So I would not rush to a conclusion and assume that there is a role for Keytruda here. I have no idea!
Olga
D.ap
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Re: Meng from China-Dx 2008 (PD-1 therapy)

Post by D.ap »

Lisa
It was truly kind of you to include us in this wonderful new!

The scans are amazing and encouraging to say the least.

Keytruda is gaining interest here in the US and my hope is that it can stabilize and shrink ASPS patience who do need the lung relief.

My question is how is Meng feeling ? The seven years have not been at all kind and Meng has been so brave and diligent in attacking the ASPS.

Were there antibiotics and or blood thinners given to help the fungal infection and is it still being treated today ?

Was the infection found by a or a scope of sputum culture after the 4 th treatment of keytruda?



What was the thinking behind taking a TKI along with a PD1 medicine ?

Wouldn't the cediranib prevent the delivery of Keytruda since it is restricting vessel production?
Enough questions
I am truly happy for Meng for the better breathing today :)
Hugs to you both

Write when you can
Love
Debbie
Debbie
D.ap
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Re: Meng from China-Dx 2008 (PD-1 therapy)

Post by D.ap »

Lisa and Meng
I didn't want to clutter up your post with articles so I posted to other medical articles which is set up on the forum for non related ASPS issues however are important for us to know
I'm not a doctor or health person but maybe someone who is will see this article and help us to begin to understand how to attack ASPS. :)

Love
Debbie
http://www.cureasps.org/forum/viewtopic.php?f=3&t=1171

Adaptive Immune Responses to Fungal Infections

http://www.cureasps.org/forum/viewtopic.php?f=2&t=1172

The PD-1/PD-L costimulatory pathway critically affects host resistance to the pathogenic fungus Histoplasma capsulatum
Debbie
D.ap
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Re: Meng from China-Dx 2008 (PD-1 therapy)

Post by D.ap »

On another note Lisa I know that histoplasmosis can look like a lesion on a scan and I wonder if Meng might of had these in her lungs and they reacted when the PD drugs as well as the chemo were applied to the her lungs?

Just a thought. But the good news is it cleared Mengs lungs of some obstructions and her cough and breathing are much improved. :D

My dad had COPD and had a histoplasmosis benign tumor removed. His was a result of breathing bird feces and it had become calcified over the years.

When our son Josh was dx in August of 2012 we were hoping the lesions in his lungs were the histoplasmosis.. but after surgery of the removal of over 150 tumors in Germany , only then did we know that wasn't the case.
Debbie

his·to·plas·mo·sis

/ˌhistōplazˈmōsis/

noun
1. infection by a fungus found in the droppings of birds and bats in humid areas. It is not serious if confined to the lungs but can be fatal if spread throughout the body.
Debbie
Lisa
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Re: Meng from China-Dx 2008 (PD-1 therapy)

Post by Lisa »

Hi Olga,
Chemo therapy lungs infusion is widely used in China. I'm not sure whether it is same with the therapy you mentioned done in Europe before.

Hi Debbie,
Thank you for sharing the articles :)
Meng feels good now but during 4 times PD therapy, she suffered from serious sides effects.
Yes, antibiotics were given to help the fungal infection, after which she stopped coughing. Now she is not given antibiotics.
The infection was found after the 4th treatment of Keytruda but not sure when the infection started as she had increasingly serious cough with the treatment.
Well, as for taking a TKI along with a PD1 medicine, that is mainly because of her alarming condition. at that time, the largest tumor in lung was larger than 6cm. She didn't stop taking TKI when she using Keytruda to make sure at least, one of them would be effective. This is just an attempt..not many theories behind this actually..
I'm not sure about histoplasmosis you mentioned..maybe I need to talk with her about this later
D.ap
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Re: Meng from China-Dx 2008 (PD-1 therapy)

Post by D.ap »

Hi Lisa and Meng

I'm truly glad to hear Meng is doing so well and feeling better. :D

I've been reading some articles on fungal infection which happens frequently with people with the autoimmune and or compromised immune symptoms and noticed that Gamma inferon drugs are used in some of their treatments to aid in boosting the immune system to fight infections. You and I are exposed to molds etc every day however we have stronger immunity than Meng and other sarcoma patients who've had treatments.


http://www.sciencedaily.com/releases/20 ... 090816.htm


We've had somewhat success with inferon-a drugs in past with the lung tumors.

http://www.cureasps.org/forum/viewtopic ... =768#p4588

The scans you provided showed some very reactive happenings in Mengs lungs with the lesions. The lesions in early September were very large for some reason and were much better than before by the last of November after being off Keytruda.

Just a thought. Could Meng have been given gamma interferon?

Also I'd be very interested to know of the lung chemo treatment .
We have some cancer centers that perform treatments to a targeted tumor or tumors in the lungs with chemo and radiation and or the whole body inc lung with chemo .

There are studies and IV chemos being performed on livers , colons etc where known arteries and veins are known to feed. All in hopes of treating the tumors directly.

http://www.cancercenter.com/lung-cancer ... emotherapy

Love
Debbie
Debbie
D.ap
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Re: Meng from China-Dx 2008 (PD-1 therapy)

Post by D.ap »

Found an article on pseudo progression in solid tumors and PD 1 drugs were included :)

http://www.cureasps.org/forum/viewtopic ... 8808#p8808
Debbie
Olga
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Re: Meng from China-Dx 2008 (PD-1 therapy)

Post by Olga »

It is a good article, explains what we were talking about, pseudo-progression and delayed response.
Re. lungs chemotherapy - called Isolated Lung Perfusion here, its status in US for Pulmonary Metastases is Phase I clinical trial was done but the results are mixed no obvious success, toxic for the lungs:
https://www.ncbi.nlm.nih.gov/pubmed/26611511
Olga
jenhy168
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Re: Meng from China-Dx 2008 (PD-1 therapy)

Post by jenhy168 »

Hi Lisa,

How old is Meng from china?

Amazing to see that the combination of her treatment is giving great results!
rachelve
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Re: Meng from China-Dx 2008 (PD-1 therapy)

Post by rachelve »

This combination is not so surprising, as there are currently a number of clinical trials combining immunotherapy drugs and TKI drugs for kidney cancer patients with success. Also, I'd say your friend's results look like a classic pseudoprogression followed by a response to the PD-1 therapy combined with the cediranib. It is also a known phenomenon at this point that immunotherapy drugs can continue to work even after therapy is discontinued. This is the case with a friend of mine with ASPS who was on PD-L1 combination trial with MEDI4736 and tremeluminab. She had to discontinue the trial due to grade 3 colitis caused by the tremelimumab. Despite the fact that she was only on the trial for a couple of months and has now been off the trial for several months, she continues to show a response even though she is not on any therapy right now as she recovers from the severe colitis.

As for whether your friend should go back on the PD-1 inhibitor, it depends on why she discontinued it to begin with. Maybe she would tolerate it better with her fungal infection healed. She also seems stronger now and at a healthier weight. It really is up to her if she wants to try it again. In addition, like I said before, the PD-1 therapy could still be having an effect. There really is no way to know that, though.

Thank you for sharing this amazing success story!! I wondered if this combination would work as well for ASPS patients as it seems to work for kidney cancer patients. It really is an exciting time now! We are just at the beginning stages of learning about the potential uses for immunotherapy and the potential for combination therapies. There are so many unanswered questions still and so much hope for the future!!
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