My son is diagnosed with stage IV high risk neuroblastoma, currently finishing 5 cycle of chemotherapy and surgery. To skip high dose chemo and BMT, I am planning to continue Hu3f8 treatment @ Memorial sloan kettering but the amount of treatment cost there is quite large, are there any alternative treatment?
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This is such a tough question to get, I assume you are high risk (either stage 3 nmyc amplified or stage 4)
The hu3f8 trial appears to be opening in a bunch of centers per
From the trial it looks like it is recruiting in Indiana as well and maybe Spain. I would recommend contacting all the hospitals and reporting back here if possible. The only other option for humanized antibody is St. Judes who have humanized ch 14:18, my understanding is that treatment in St. Judes is very cheap if you can get there.
Skipping high dose chemo is such a difficult question. The reason they have 1 (and now COG are standardising on 2) transplants is cause the research they had to date showed that it significantly helped with event free survival. The problem though is that this survival does not come free, there are long term side effects and the heavier the treatment the higher the risks are.
MSK donāt really like event free survival as a metric and usually try to look at overall survival which makes comparing research a bit more complicated.
That said none of the research COG have involves humanized antibody and vaccine like they have at MSK so we are comparing 2 completely different protocols here and deciding is very tricky.
If I knew I was going to continue on MSK protocol I would highly recommend consulting with them ASAP and getting a similar chemo protocol as they offer at MSK, all the chemo drugs are widely available and that part of the protocol is very standard.
If the operation post surgery is super complicated I would recommend getting a second opinion from MSK.
So, I guess, if you want to do the MSK protocol and get hu3F8 I would recommend you follow their protocol as closely as possible including skipping transplant. Otherwise you are in some kind of no-mans land protocol wise which is not ideal.
If it is prohibitive financially to go with the MSK protocol I guess the best you can do is stay with a SIOPEN or COG protocol and consult your oncologists. Then your only big decision point will be deciding on one transplant vs 2, and there are already enormous variables there. There are not guarantees that NB will even respond to chemo and if it responds you donāt even know how well it will respond.
I know it can be super overwhelming in your shoes with so many opinions everywhere but there is no 1 answer that can fit every single case.
Are you located in the US already? What protocol are you one? Where are you being treated?
From the genetics test my son have stage 4 with Nmyc non-amplified type, is that a good news for prognosis factor?
Currently my sonās doing his treatment at NUH singpore. Iām not sure which protocol they use, what I know the use combination of CAV (vincristine, cyclophosphamide, doxorubicin) and EP (etoposide, cisplatin) in 5 cycle of chemotheraphy. The PET CT scan results after 4 cycles shows excellent response. Now Iāam waiting for the scan and Bone marrow test results after the 5th cycle.
Already contacted and send his medical records to MSK.
MSK already give the recommendation to go straight to 5 cycle of Hu3F8 treatment without high dose chemotheraphy and bone marrow transplant. But they require everything to be deposited in advance before starting treatment in U.S. I have to decide wether can make the deposit on time or continue to collect stem cells and proceed to high dose chemo at NUH singapore.
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thanks for all the answers i found here guys. but a quick answer to the question it is safe to skip high dose chemotherapy and BMT i can say: it is never safe to keep high dose of chemo but stage IV is not safe either. as other people suggested, try to search for the best alternative. good luck!
Hi Fahiem, my son was diagnosed with NB stage IV with NMYC amplified in July 2015, and he has gone through all treatments (Chemo, Surgery, BMTļ¼RT and Isotretinon for 6 month) in Singapore KKH. My son completed the treatment in Jun 2016 and so far all the three month check up is fine.
I believe both NUH and KKH follow COG standard for Neuroblastoma treatment, with is CAV+PE 5 chemo for stage 4 patient. for your case I am not sure whether Dr. Miriam suggestted you to do BMT or not. but MSK 3F8 do have an advantage that patient is not required to do the BMT before the 3F8 (if patient choose CH14.18, they need to complete BMT and RT before processing the CH14.18).
at the moment, 3F8 is available in several places which operated by doctor came directly from MSK. I will suggest the Spain Hospital Sant Joan De Deu as I have several China Neuroblastoma patient friends are doing the 3F8 treatment there. Compared to MSK USA, the 3F8 treatment fee in Spain is acceptable, estimated 300-400K SGD.
feel free to contact me and I would like to share more information with you. Hope your little buddy can recover soon.
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Hi Bahasuan. My son is in the similar situation. Diagnosed(14 months old) as Stage IV with NMYC amplification. It seems he achieved CR after Chemo and Surgery. We contacted Barcelona with Dr. Mora. But they donāt enroll first remission patient except with residual disease in bone or bone marrow.
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Hi, I already contacted the SJD hospital in barcelona, and the hospital proposed Hu3f8 treatment for my son without the high dose chemotherapy and Bone marrow transplant. By the way is there any significant difference between nmyc amplified and non-amplified on stage IV neuroblastoma?
AFAIK the biggest factor to keep in mind is how well the tumor responded to frontline chemotherapy and how much is left after surgery.
Hi Alex,
Please could you let me know more about the hu3f8 charges in the Barcelona hospital. Is the amount you mentioned above for each session or the overall amount they charge for the full treatment ?
Thanks
Dear Sumera,
Now Spain SJD is still under trail, so the medicine is free of charge.
The total fee of this hu3F8 clinical trial is about 165,000 Euro. You can leave the message on the hospital website and they will contact you.
Alternatively, I have personally assisted a few China patient to consult the 3F8 treatment in Spain and some of them is doing the treatment here. If you donāt mind to show me the details of your daughter, I can also do the same initial consultation for you. Once hospital confirm they can accept your daughter, I will leave you contact the hospital by yourself.
I do this for free, just want to help the parents of Neuroblastoma patient.
Regards
Alex Chen
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We are struggeling with this question aswell. Our daughter (high risk, stage 4, Nmyc non-amplified) is in the Dutch DCOG NBL 2009 Treatment Protocol. This is roughly based on the German GPOH NB97 trial. The protocol consists of:
6 chemotherapy
surgery
radiation therapy
ASCT
immune therapy CH14.18
Unfortunately she developed a severere pneumonia after her 4th cycle of chemotherapy. She was taken to the IC-unit. This happened again after cycle 5 and 6. The doctors think she has developed some auto-immune reaction. Her own neutrophils āattackā her lungs causing an inflammation. This is why it is risky to give her Neupogen or Neulasta, medicins they usually give patiens to help them get out of neutropenia. (But also for harvesting stem cells).
But now: our doctors think the high dose is too risky. They think she will definitely will develope a new severe pneumonia, combined with pulmonary hypertension. So they recommend a few more rounds of maintenance chemotherapy (low dose) insteadā¦ They think here chances are still good, because the first 6 rounds of chemo made all here metastases go away. There is no evidence of minimal residual disease.
So she will get surgery, probably radio therapy, and then immune therapy (CH14.18).
We are very scared this is not enough to cure here. But they showed us this research paper, that they think should convice us that maintenance therapy instead of ASCT can still work: Long-term outcomes of the GPOH NB97 trial for children with high-risk neuroblastoma comparing high-dose chemotherapy with autologous stem cell transplantation and oral chemotherapy as consolidation | British Journal of Cancer .
But reading this paper makes me even more unsure if this is the right choice.
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MSK that is considered one of the best hospitals in the world to be treated for NB stopped doing transplant many years ago and have very good success rates (and access to some more potent immunotherapy agents).
There are plenty of open questions on transplant, now that 2 transplants are considered ābetterā what about 3? What is the impact on overall survival vs event free survival of transplants? What about new drugs like humanized antibodies do they change the results?
Keep in mind every case is unique. Even pre chemotherapy a tiny amount of kids used to survive. The doctors are constantly trying to balance the cost of the highly toxic treatment vs potential benefits.
If your doctors think it is extremely risky to go with ASCT I would personally trust them. If you are concerned here you could try for another opinion.
One thing though I would recommend exploring would be access to hu3F8 which is far more potent than CH 14.18 and being trialed now in Europe. This would at least place you on a protocol that is more similar to what they run at MSK (which does not include ASCT)
Thanks for your reply Sam. I am curious about hu3f8: do you know of any studies done by researchers outside MSK which confirm that this is the better immunotherapy?
I wrote a bit about clinical trials here: How do you pick which clinical trials to join?
hu3F8 is still just in Phase 2. So we know what dosages we can give, and we can measure there is a lot of antibody in the blood. Butā¦ it is going to take another 5 years until long term studies are published.
MSK have graphs that they share yearly and the graphs they share comparing 3F8 to hu3F8 always show a marked improvement when they introduced hu3F8.
ch14.18 is quite an intense experience, involving a week plus of hospitalization (for standard non long term infusion). hu3F8 in comparison is a day visit to the hospital and a 1 hour infusion after which you go home.
The big ray of light here is that an international trial is in progress: Naxitamab for High-Risk Neuroblastoma Patients With Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow - Full Text View - ClinicalTrials.gov
SJD in Barcelona, Spain has been conducting the Hu3F8 trial for over 1 year. This is the first site outside USA, or outside MSK.
Y.mAbs are opening new sites this year, including a few hospitals in the United States from last year and a few new sites in Europe (Madrid, UK, Denmark).
They need to share some prelimary date for the effectiveness of the antibody. If you read the trial information given by Sam at clinicaltrials.gov, you will notice that the the participants need to have disease in bone/bone marrow in order to be enrolled in the trial. Also, parents who did Hu3F8 at MSK said that Hu3f8 is more effective to treat bone/bone marrow residual disease.
According to the official website of Y.mAbs Therapeutics, Dr. Claus Moller, Chief Executive Officer, continued, āWe are pleased to see that the clinical data previously generated at MSK was able to be replicated at other sites. We believe that an ORR of 73% may place naxitamab in a strong position in the market for the treatment of high-risk neuroblastoma.ā
Also, the company (together with MSK) will present data at international conferences.
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