When I relapsed for the 3rd time in May 2015 after my ASCT in November 2013, having been brought to very good partial remission (VGPR) on Velcade, dexamethasone and Revlimid, my doctor arranged for me to speak to the people running a daratumumab clinical trial.
I reviewed their 42 page consent "form" and discussed it with my nephew, who is also a hematology oncology specialist and co-director of a bone marrow transplant program.
Daratumumab has also been funded by J&J for clinical trials at 48 locations around the US and they are pushing hard to get FDA approval asap.
However, it has serious site reaction, infusion reaction, and allergic side effect potential consequences. Plus, you are tied to the infusion site for up to 2 years, and the first infusions can run for over 20 hours.
The consent form said the trial will have 135 people, the first 6 of whom will be given the drug at one dose. The next 29 will be given a lower dose, and then the dosage will be further reduced for the remaining 100!
I was given no assurance that I would not be in the first 6 or 29, who will be guinea pigs for the 100!!
As Pomalyst, the improved drug over Revlimid, is available, and carfilzomib (Kyprolis), the improved drug over Velcade, has been out since 2012, I chose to go with those two FDA-approved drugs, plus dex, as the first step for now.
I am on 3 weeks on / 1 week off with the carfilzomib IV on Wednesdays and Thursdays; Pomalyst daily orally, and dex 5 pills morning and evening on days 1 and 8 of the 21 day cycle.
My IgA went from 800 in May to 1800 in June to 3300 in July. After only the first 2 shots IV of the carfilzomib, it dropped to 1600, and my beta 2 microglobulin and lambda/kappa ratios back down to 2.4 and 2.5, respectively, from 19 and 12, respectively.
I urge you to discuss the use of FDA approved evolutions of Revlimid and Velcade that are proven to have less of their side effects.
Daratumumab will soon emerge from the trials and, for FDA approval, they will have to clean up the side effect risks. It could be available by late this year or early 2016. If you can buy time with the FDA-approved drugs, you will have the choice of an approved monoclonal antibody when relapse next occurs.
That is my game plan and it appears to be, Thank God, working.
It is criminal that the "standard of care" puts people on Velcade and Revlimid first, knowing that Velcade nearly always causes neuropathy, while carfilzomib has a much lower risk of it. Pomalyst has some of the circulatory side effects of Revlimid, but is a far superior drug. Celgene developed it at the same time as Revlimid, but held it back so they could milk Revlimid for as long as they had patent protection.
Doctors are forced to follow the standard of care even when they know that better, less risky and more effective meds are available. It is sad that between the lobbyists, big pharma, insurance companies, lawyers, doctors and hospitals, the only ones a patient can count on are themselves and their loved ones, who must ask the critical questions and insist on answers.
Why is this good for me?
What else is available?
What if I do not do this?
Where can I get another opinion?
What are the risks and probabilities?
Where can I read more about this?
Forums
Re: RVD + SCT, or trial of Revlimid, dex, and daratumumab?
Thanks for all the input! With so many "new" drug options in myeloma treatment emerging, it is so hard to know what is the "best" option. I'm sure in 5 years doctors will know more and be able to tell patients what they should do. But, right now as patients, it's difficult to navigate the options as they keep coming out with next best thing. Still waiting for the cure though!
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lys2012 - Name: Alyssa
- When were you/they diagnosed?: 2010, Toronto, Canada
- Age at diagnosis: 32
Re: RVD + SCT, or trial of Revlimid, dex, and daratumumab?
Hi Lys,
I'm glad you've gotten so much feedback in regard to your question. I'm hesitant to add to the discussion, but I think there are some things that need to be cleared up after edhaydin's posting earlier in this thread.
First of all, I think it's a dramatic overstatement to say that daratumumab has "serious site reaction, infusion reaction, and allergic side effect potential consequences". There were presentations at the recent ASCO and EHA meetings that summarized results of a major daratumumab trial. The presentations are available here at the Beacon. Here's a link to the ASCO presentation:
https://myelomabeacon.org/docs/asco2015/8512.pdf
There's a page in the presentation focused solely on infusion reactions. You'll see there that about 45 percent of the patients in the trial experienced infusion reactions. However, in almost all cases, the reactions were considered mild or moderate (Grade 1 or 2, where Grade 3 and 4 are considered serious and severe). Also, the reactions occurred almost solely during the first infusions patients received.
Most importantly, no patient in the trial discontinued treatment due to the infusion reactions.
Second, the trial design edhaydin talked about for the trial he considered, which was a Phase 1/2 study, is standard for those sorts of trials. Part of what researchers do in Phase 1 trials is try to establish the safest, most effective dose of the drug. Just about every myeloma drug out there that is in regular use today has gone through a Phase 1 trial, where patients are randomly allocated to receive different doses to shed light on the drug's safety and efficacy.
Just as we can't tell for sure from test tube and animal studies whether a drug will really be effective against myeloma when it's used in human patients, we also can't know from test tube and animal studies what the safe and effective dose of a drug will be. So, when drugs are being tested in people for the first time, researchers have to experiment with different doses.
I'm sure for the trial you're considering, however, that there is probably just one dose of daratumumab being tested, and it's a dose that's been established based on exactly the sort of Phase 1 testing that has helped researchers figure out what the best dose is likely to be.
Finally, while some people may feel that they know better than myeloma specialists and hematologist-oncologist who have been treating patients for decades, there may well be good reasons why doctors continue to treat newly diagnosed myeloma patients primarily with Revlimid and Velcade. There are no data out there, for example, for Pomalyst when it comes to using it to treat newly diagnosed myeloma patients. And, while Kyprolis may not cause as much neuropathy as Velcade, there are other safety concerns when it comes to Kyprolis; see, for example, this posting by Tracy J about her recent experience with Kyprolis.
I realize your choice is by no means simple, but I also think the arguments in favor of considering the daratumumab trial are more compelling than some here have painted them to be.
Good luck with your choice, and please keep us updated about what you decide.
I'm glad you've gotten so much feedback in regard to your question. I'm hesitant to add to the discussion, but I think there are some things that need to be cleared up after edhaydin's posting earlier in this thread.
First of all, I think it's a dramatic overstatement to say that daratumumab has "serious site reaction, infusion reaction, and allergic side effect potential consequences". There were presentations at the recent ASCO and EHA meetings that summarized results of a major daratumumab trial. The presentations are available here at the Beacon. Here's a link to the ASCO presentation:
https://myelomabeacon.org/docs/asco2015/8512.pdf
There's a page in the presentation focused solely on infusion reactions. You'll see there that about 45 percent of the patients in the trial experienced infusion reactions. However, in almost all cases, the reactions were considered mild or moderate (Grade 1 or 2, where Grade 3 and 4 are considered serious and severe). Also, the reactions occurred almost solely during the first infusions patients received.
Most importantly, no patient in the trial discontinued treatment due to the infusion reactions.
Second, the trial design edhaydin talked about for the trial he considered, which was a Phase 1/2 study, is standard for those sorts of trials. Part of what researchers do in Phase 1 trials is try to establish the safest, most effective dose of the drug. Just about every myeloma drug out there that is in regular use today has gone through a Phase 1 trial, where patients are randomly allocated to receive different doses to shed light on the drug's safety and efficacy.
Just as we can't tell for sure from test tube and animal studies whether a drug will really be effective against myeloma when it's used in human patients, we also can't know from test tube and animal studies what the safe and effective dose of a drug will be. So, when drugs are being tested in people for the first time, researchers have to experiment with different doses.
I'm sure for the trial you're considering, however, that there is probably just one dose of daratumumab being tested, and it's a dose that's been established based on exactly the sort of Phase 1 testing that has helped researchers figure out what the best dose is likely to be.
Finally, while some people may feel that they know better than myeloma specialists and hematologist-oncologist who have been treating patients for decades, there may well be good reasons why doctors continue to treat newly diagnosed myeloma patients primarily with Revlimid and Velcade. There are no data out there, for example, for Pomalyst when it comes to using it to treat newly diagnosed myeloma patients. And, while Kyprolis may not cause as much neuropathy as Velcade, there are other safety concerns when it comes to Kyprolis; see, for example, this posting by Tracy J about her recent experience with Kyprolis.
I realize your choice is by no means simple, but I also think the arguments in favor of considering the daratumumab trial are more compelling than some here have painted them to be.
Good luck with your choice, and please keep us updated about what you decide.
Re: RVD + SCT, or trial of Revlimid, dex, and daratumumab?
Good post by TerryH. Here is a recent paper describing a small group of 23 relapsed patients with respect to the cardiac toxicity of carfilzomib.
Reference:
D Sophia et al, "'Real Life' Experience of Pre-Approval Carfilzomib-Based Therapy in Myeloma - Analysis of Cardiac Toxicity and Predisposing Factors," European Journal of Haematology, Sep 2, 2015 (abstract)
Results:
Overall response rate was 65% with a median progression free survival of 6.0 months and a median duration of response of 6.8 months, respectively. Median overall survival was 14.9 months. Grade 3/4 adverse events occurred in 50% of patients with 23% experiencing left ventricular failure. The risk of cardiac adverse events was markedly increased after previous radiotherapy of the thoracic spine and concomitant administration of doxorubicin.
Conclusion:
Carfilzomib-based treatment is efficient in advanced multiple myeloma. In our "real life" patients, we found considerable cardiotoxic effects in some cases, indicating a need for careful patient selection and close monitoring of the at-risk population."
Reference:
D Sophia et al, "'Real Life' Experience of Pre-Approval Carfilzomib-Based Therapy in Myeloma - Analysis of Cardiac Toxicity and Predisposing Factors," European Journal of Haematology, Sep 2, 2015 (abstract)
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Mark11
Re: RVD + SCT, or trial of Revlimid, dex, and daratumumab?
Just wanted to post a brief update. I talked to my doctor about this a few months back. First talked with the fellow, then my doctor.
In my case, I had a "dramatic" response to Velcade, which my doctor said was truly a game changer for myeloma. So they would rather retry Velcade again, with the addition of Revlimid and lower dose dex, then move on to a new line of treatment. In this case the trial of daratumumab, which the doctor said has not had such a great improvement as Velcade did for patients; he has not been that impressed by results he is reading.
Hope that makes sense. Going for my follow-up in a few weeks and see where my M-spike is. Hovering around 10 (or 1.0 in U.S. terms).
In my case, I had a "dramatic" response to Velcade, which my doctor said was truly a game changer for myeloma. So they would rather retry Velcade again, with the addition of Revlimid and lower dose dex, then move on to a new line of treatment. In this case the trial of daratumumab, which the doctor said has not had such a great improvement as Velcade did for patients; he has not been that impressed by results he is reading.
Hope that makes sense. Going for my follow-up in a few weeks and see where my M-spike is. Hovering around 10 (or 1.0 in U.S. terms).
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lys2012 - Name: Alyssa
- When were you/they diagnosed?: 2010, Toronto, Canada
- Age at diagnosis: 32
Re: RVD + SCT, or trial of Revlimid, dex, and daratumumab?
Hello Lys:
Just wanted to comment on your daratumumab opportunity for a trial. Most of the top doctors in the US are very optimistic about it. Now that it has been improved in the US, I would expect news coming out in clinical settings as to whether or not it lives up to its promise (or "hype", if you prefer).
Just wanted to feed that back to you, to look into it a little more, even if in your case your doctor may not have been fully informed. Sometimes you have to push the doctors to make sure that they are on top of the latest research relevant to your case.
Actually, getting good data on the daratumumab, Revlimid, and dex combo is also very valuable for the research. Daratumumab has good results by itself / alone, but not all of the combinations have been fully tested yet, and some doctors are very optimistic about the potential. However, some good clinical trials would be helpful also in advancing the field.
Good luck to you.
Just wanted to comment on your daratumumab opportunity for a trial. Most of the top doctors in the US are very optimistic about it. Now that it has been improved in the US, I would expect news coming out in clinical settings as to whether or not it lives up to its promise (or "hype", if you prefer).
Just wanted to feed that back to you, to look into it a little more, even if in your case your doctor may not have been fully informed. Sometimes you have to push the doctors to make sure that they are on top of the latest research relevant to your case.
Actually, getting good data on the daratumumab, Revlimid, and dex combo is also very valuable for the research. Daratumumab has good results by itself / alone, but not all of the combinations have been fully tested yet, and some doctors are very optimistic about the potential. However, some good clinical trials would be helpful also in advancing the field.
Good luck to you.
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JPC - Name: JPC
Re: RVD + SCT, or trial of Revlimid, dex, and daratumumab?
Thanks for the feedback.
I am ok with Velcade, as the first round cut my M-protein by 75% and side effects were not that bad for me. But it does not hurt to get other opinions.
When it comes time to start treatment, I could ask for a referral to speak to the doctor doing the trial. She used to be my doctor, but she moved on from regular clinic to focus on research.
As stated before, I'm in Canada, so things are a bit different here as to what drugs are approved and for when.
I am ok with Velcade, as the first round cut my M-protein by 75% and side effects were not that bad for me. But it does not hurt to get other opinions.
When it comes time to start treatment, I could ask for a referral to speak to the doctor doing the trial. She used to be my doctor, but she moved on from regular clinic to focus on research.
As stated before, I'm in Canada, so things are a bit different here as to what drugs are approved and for when.
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lys2012 - Name: Alyssa
- When were you/they diagnosed?: 2010, Toronto, Canada
- Age at diagnosis: 32
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