Hello everyone, I've learned so much from this site already but now I have some more detailed information I'm wondering if anyone can help me with some specific advice (I apologise for the long post now)
My 19 year old daughter was in her first tern at Uni when she was diagnosed with Glioblastoma Multiforme in October, She had a craniotomy early November and most of the biggest tumour was removed. She then had the standard 6 weeks of radiotherapy (18 full brain, 12 targeted) with Temozolomide. She's had a month off and just had her first double dose 5/23 chemo (and she's been horribly sick with it and has zero appetite)
We were hoping to go down the DCVax route but it looks as though there might not be enough frozen tumour material to make a full vaccine (and we're gutted)
We had an Oncologica biomarker report and it looks like her mutations are ATM, TSC1 and TP53, her PD-L1 tumour proportion score is 90-95%, PD-L1 positive ICs 1% of tumour area (which I'm told suggests she'd be a good candidate for immunotherapy)
In terms of what Laura's currently taking, she's takes FECO 3 times a day, Keppra, Chloroquine and she's also on the Care Oncology protocol (Metformin, Atorvastatin and Vermox)
Supplement wise she also takes;
Boswellia
Berberine
Bromelain
Longvidia Curcumin
Milk thistle
Melatonin
Artemisia
Vitamin A D K
Resveratrol
Grapeseed
So the reason for the post is to ask if any of you wise people have any suggestions as to where we could look next? I think we might struggle with dendritic cell therapy due to the small sample size but is it possible to get hold of immunotherapy drugs or is that only an option if you're on a trial?
Laura was just getting started in her life and I'll do whatever I can to give her the best possible change of a happy life.
Thanks very much for reading and best wishes to you all
Nicola x
Hi Nicola,
ReplyDeleteMy son was diagnosed with GBM 3 years ago when he was 19. I am so sorry that your 19 year old daughter is going through this same terrible ordeal. Since your PDL1 score is >90%, you should try to use any anti-PDL1 drug off label. My son is negative for PDL1. He was on keto diet for 6 months, he has been using various re-purpose medication including disulfiram, low dose Naltrexone, celecoxib, cimetidine, dichloroacetate (DCA). He was also on medical marijuana (but you will not want to take anti-PDL1 drug and medical marijuana at the same time).
Best wishes to your daughter...
Holly
In IOZK, we work with NDV/hyperthermia-induced serum-derived antigenic extracellular microvesicles to use as antigen for loading the dendritic cells. So we do not need tumor tissue for preparing the vaccine. On top of that, using the original tumor now after radiochemotherapy is in fact possibly using historical tumor antigens and not actualized tumor antigens. That is why we developed this technology. We have also a schedule running to integrate NDV/hyperthermia already during the TMZ maintenance chemotherapy. These data were published last year. I hope this helps at this stage.
ReplyDeleteHi Nicola,
ReplyDeleteI'm sorry to hear of your daughter's diagnosis and the fact that she isn't tolerating the adjuvant chemotherapy well. Hopefully she'll feel better after the 5 days of chemo.
According to the Oncologica info, "A range of cut-off/threshold values for tumour proportion scores (>1%, >25%, >50%) and PD-L1 positive immune cells (>10%) have been identified as predictors of response to anti-PD-L1 directed therapies."
A tumor proportion score of 90-95% is very high, and I would definitely look into the possibility of immune checkpoint inhibitor therapy (in GBM this usually means anti PD-1 or PD-L1 drugs, such as nivolumab, pembrolizumab, durvalumab etc.)
These drugs are approved for other types of cancers, but not for brain tumors, but they could be used "off-label" for brain tumors outside of a clinical trial. The major question with off-trial use is usually who will pay for it (these drugs are very expensive).
Am I correct to assume you're in the UK? (considering you had sequencing done with Oncologica)
If so, in your situation I might reach out to Dr. Paul Mulholland (in addition to your daughter's oncologist) to discuss the possibilities for immune checkpoint inhibitor therapy. Mulholland has published studies on the use of checkpoint inhibitors for GBM patients in the UK.
https://www.nature.com/articles/s41416-018-0258-8
http://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.e13514
Often GBM in adolescence has a mutation called H3F3A G34 (or H3 G34 for short), as well as ATRX. I've reached out to Oncologica to ask if these 2 genes are part of their standard panel.
As for clinical trials, it's too for most newly diagnosed trials as she's already started adjuvant chemotherapy. She'd be eligible for trials for recurrent disease if her tumor progresses on or after her current therapy. In the meantime I'd look into off-trial use of immune checkpoint inhibitors.
An alternative to using a checkpoint inhibitor now would be to save it for a clinical trial in combination with a vaccine, such as this one:
https://clinicaltrials.gov/ct2/show/NCT03665545 (recruiting in Geneva Switzerland)
There's also an interesting trial for recurrent GBM recruiting in France:
https://clinicaltrials.gov/ct2/show/NCT03294486
The first of these trials is only recruiting 24 patients, and there's no guarantee it would still be open if/when her tumour progresses. As it includes pembrolizumab in the trial, it excludes any patients who have had prior use of anti PD-1 or PD-L1 therapies. The trial is also randomized so half the patients get vaccine + Poly ICLC and the other half get pembrolizumab + vaccine + Poly ICLC.
Let us know if you're able to get further info on the availability of checkpoint inhibitors outside of a trial. Best wishes to you and your daughter.
Hello Nicola--
ReplyDeleteI'm truly and deeply sorry that you and your daughter are going through this. I'm chiming in to share my husband's experience with the first round of higher-dose TMZ. He too, was terribly nauseous. What we learned that significantly improved future rounds was to proactively medicate him for nausea--take it round the clock before the nausea began . In his case, he took ondansetron (Zofran) 8 mg three times a day (max dose). He had rare breakthrough nausea at that dose for which he took prochlorperazine (Compazine). So long as we got ahead of the nausea, rather than chase it, it became quite tolerable. (But do stay ahead of the constipation, too). Best of luck, hope and healing--S.
Hi Nicola. I'm very sorry to hear about your daughter's diagnosis. I'm nevertheless glad to learn you are taking such a proactive stance right from the start, which I think is a very good thing.
ReplyDeleteWould private oncology clinics with immunotherapy / virotherapy treatments be an option for you / your daughter potentially? I am asking as I am personally undergoing such a treatment at IOZK clinic in Cologne, Germany, since January last year, and I was in a similar situation as your daughter with lack of frozen tumor tissue to produce the vaccine with. However, at IOZK they produced a vaccine based on liquid biopsy (i.e. from blood), for which no tumor material is necessary.
Obviously we are not talking a treatment with any ph-III study data to verify efficacy, but I am convinced it's working for me (at least in combination with my extensive supplement / med cocktail). I'm progression-free since Sep 2017 OP so far, and very happy with the treatment at the clinic. No side effects. They also work with PD-1 inhibitors where appropriate / necessary.
If it's an option for you logistically & financially, I would personally recommend this clinic based on my own experience.
All the best wishes to your daughter, and wish you all lots of strength for the road ahead.
Best,
John
How much tumor tissue is saved? I am aware that the clinical trials used 2-3 grams, however at various symposiums the company has stated that vaccines have been made with 1/10th of a gram. In a 9 patient smaller study, when the vaccine was combined with imiquimod which is a $250 immunotherapy skin cream, 5 patients are still alive 5 years out. Additionally in the larger clinical trial, patients who lived the longest were of the "mesenchymal" group. This group has low Pd1. PD1 is a chemical released by the tumor to neutralize white blood cells. High PD1 is treated sucessfully with NHS approved keytruda or opdivo. This suggests a combo therapy of DCVax and Keytruda or Opdivo (and imiquimod).
ReplyDelete