[Mark11]

Progress toward a multiple myeloma cure?

by Mark11 on Sat Nov 07, 2015 11:23 am

I have been posting here for 4 plus years since my diagnosis and I am now a 5-year survivor and I am currently doing very well – myeloma therapy free, and a sustained molecular response for over 4 years. My reason for posting this is mostly for newly diagnosed younger patients to show how SLOWLY things change in myeloma therapy.

Back when I first started posting here in the forum, the "hot topics" were maintenance therapy, upfront or delayed autologous transplant, and just starting at the time I started posting was the question of whether depth of response (MRD testing) would increase overall survival/cure some patients.

Sound familiar?

Another comment that I heard a lot was that I should not have pursued an upfront allo (allogeneic, donor) transplant because the "myeloma thought leaders" were saying we were close to curing myeloma without the need for therapies like allo transplant, and that patients should not treat aggressively early to "save themselves" for the curative therapies that were to come. We hear those comments as well today. Some of the potential cures we discussed in the last four years were JQ1, measles vaccine, CAR T cells and others I have forgotten about.

With that in mind I went over to the ASH 2015 abstracts page to see if there was any evidence that myeloma patients are currently being cured or at least the "myeloma thought leaders" were getting closer to curing more patients 5 years later. I did searches like "myeloma cure" and "myeloma curable" and looked for abstracts that included treatment results, not hopes for the future.

Only two therapies were mentioned as having curative potential for some patients from the abstracts I found: auto and allo transplants. I could not find any reference to a novel agent or therapy being developed / approved for use since 2010 as having shown the ability to cure a patient. Of course, they could help the therapies that have shown the ability to give patients long-term drug free remissions.

For those interested, these are the only two that mentioned curing some myeloma patients:

We demonstrated that operational cure (i.e.: >10-years PFS) was possible for 13% of transplant-eligible M​M patients before the era of novel agents. Curability rates were particularly frequent among patients with a benign phenotypic signature at diagnosis and MRD negativity after HDT/ASCT, suggesting a remarkable clinical benefit of attaining deep remissions after intensive treatment for patients with early M​M.

Source: B Paiva et al, "What Is the Frequency of Transplant-Eligible Multiple Myeloma Patients Being Cured? The Impact of an MGUS-like Signature at Diagnosis and MRD-Negativity," ASH 2015 Annual Meeting abstract # 725

Overall, the response rate after allo-SCT was as follows: CR 58%, VGPR 19%, PR 18%. Median CR duration was 10 years (44% at 15 years)."

In conclusion, this retrospective analysis performed with an extended follow-up of 13 years shows that a fraction of M​M pts can be long-term survivors after allo-SCT, one third of them being potentially cured. The best outcomes were obtained when allo-SCT was applied in pts in an early phase of their disease and with a small residual tumor size. The major challenge, both with MA and NMA allo-SCT, was the relatively high post-transplant relapse rate. The presence of cGVHD was protective for the risk of progression, supporting the role of GVM, but increased the risk of NRM. New approaches aimed at modulating cGVHD are warranted. In addition, incorporation of novel agents before and after allo-SCT to increase the rate and duration of high-quality responses, as well as identification of those patients mostly benefiting from this procedure, will likely contribute to improve long-term outcomes.

Source: E Zamagni, "Long-Term Clinical Outcomes of Allogeneic Stem Cell Trans­plan­ta­tion in Multiple Myeloma," ASH 2015 Annual Meeting abstract 1968

Hopefully they will make a lot more progress toward curing myeloma or at least providing the excellent quality of life and long-term drug free remission that allo transplant has provided for this high-risk patient. I am certainly glad I did not take the advice of going with less aggressive therapy early after diagnosis because of all of the curative therapies that would soon be arriving. They very likely would not have come soon enough for me.

Has anyone seen any abstracts they are excited about? Here is a link to the abstracts here at The Beacon. Please post them. It is important for newly diagnosed patients to see the latest research so they can make informed decisions on their initial therapy.

[Edna]

Re: Progress toward a multiple myeloma cure?

by Edna on Sat Nov 07, 2015 2:33 pm

Mark 11

I appreciate that you chose to have an allotransplant as the most likely to offer a cure for multiple myeloma and that you have personally done very well with this decision in being disease free for 5 years.

I and, no doubt, all persons batttling myeloma would love to be in the same position, but have not taken this path. Whether because we put our faith in all the new treatments that showed promise, because we did not really challenge the 'conventional' approaches as you did from your research, or we wanted a less aggressive approach with lower risks, or for other reasons.

I was informed by staff at clinic that younger people frequently have more aggressive disease in general, so the 'benign phenotypic signature' in the research you quote may not apply to all. A select group of patients may benefit, I do not know.

But I want to point you to a forum thread, "Revlimid treatment response and trisomies" (started Oct 24, 2015), where experience of people having an allo transplant does not come out quite so well.

Who is right and who is wrong and under what circumstances the allo- transplant route should be available to newly diagnosed young patients may not be quite so clear cut. This route being generally offered to some later on in the course of the treatment of the disease. An issue too is donor tissue match, not always easy to find.

Some of us are not great risk takers with treatments. You clearly are and use research to determine the option that suits your desire for a cure, that is good.

I hope you are well on the 10 year cure journey.

Edna

[Mark11]

Re: Progress toward a multiple myeloma cure?

by Mark11 on Sun Nov 08, 2015 8:04 pm

Hi Edna,

I hope you are well on the 10 year cure journey.

Come on, say what you really feel! Just kidding, thanks for saying that.

Whether because we put our faith in all the new treatments that showed promise, because we did not really challenge the 'conventional' approaches as you did from your research, or we wanted a less aggressive approach with lower risks, or for other reasons.

One of the main reasons for my post was to show newly diagnosed younger patients the risks of relying on new treatments that may never come, particularly if your goal of therapy is cure. One thing I forgot to mention in my original post was that back in 2010 we also heard about all of this new drug development. In the five years since my diagnosis, the only new CLASS of drug approved in the US for myeloma was an HDAC inhibitor (panobinostat aka Farydak). Based on what I read here in the Forum, it does not seem that a lot of patients use this therapy, but that is just an observation that may or may not be correct.

But I want to point you to a forum thread, "Revlimid treatment response and trisomies" (started Oct 24, 2015), where experience of people having an allo transplant does not come out quite so well.

What is the purpose of that sentence? Are there no bad outcomes using novel agents? No side effects from novel agents? Could you point to a post where I said 100% of patients that do allo transplants have excellent outcomes? Were these transplants done in the patients first remission? I have been clear in my posts that I would not do an allo as a relapsed patient or with active disease. Would you like me to post a link to an obituary of a younger patient who used to post here who participated in the "cutting edge carfilzomib trial for newly diagnosed patients" that constantly posted here that transplants were not necessary who died 4 years after being diagnosed to prove there are poor outcomes in patients who use the newest drugs? Patients with myeloma die / have poor outcomes no matter what therapy route they choose.

As a side note, the number of patients who do allo transplants in remission in the US is very low. To give you an idea how rare, there were 18 matched unrelated donor transplants done on myeloma patients in remission in 2011 (the year I did mine) in the US. I do not know how often they are used in remission overseas.

While there are certainly side effects from allo transplants, I doubt the validity of that poster. Strange that someone who never posts here suddenly posts in a thread about response to Revlimid that they know multiple patients who did allo transplants (including a cord blood transplant) who died/dying or are in the ICU. That poster claimed they did a transplant from an exact twin. That is not an allogeneic transplant. That is called a syngeneic transplant. Strange that someone who claimed to do one did not know that.

Mark

[Terrij]

Re: Progress toward a multiple myeloma cure?

by Terrij on Sun Nov 08, 2015 9:51 pm

I commend you Mark for posting this topic for younger patients. When my daughter was diagnosed at 32, an allo transplant was never mentioned. Having never heard of multiple myeloma, learning about the disease and treatment, it seemed the standard was induction, auto transplant, and maintenance, which she responded to very well. No one mentioned allo until she relapsed, which she prepared to do, but they felt at the time her body was not in the best shape to do. As you have said and I agree with you, statistics for allo transplant after relapse are not good. So she moved on doing clinical trials with the hope of T cell therapy. Unfortunately that did not happen.

I am not up on all the medical statistics, but I do know through experience that there are many factors going into individual treatment depending on the person. There is such a difference of opinion between doctors. There is a difference in each person's myeloma and aggressiveness of disease. No one can really predict what will happen.

I am so glad the allo worked for you. I think at diagnosis once the disease is reigned in it is probably best to hit it aggressively. Each person has to decide what is best for them and what they can handle. With the guidance of not just one opinion and research the decision can be made.

[Edna]

Re: Progress toward a multiple myeloma cure?

by Edna on Mon Nov 09, 2015 5:48 am

Dear Mark 11

I wish to point out that I am not an advocate of any particular myeloma treatment.

In honesty I would prefer not to have it or the treatment, less because I am going to die, because I have known a lot of younger people who have died, not from myeloma or cancer. I have always been physically and mentally active so the ongoing decline due to disease and drugs makes the daily things more negative. The constant attendance at hospital clinics for supportive care to deal with drug toxicities makes one aware just how abnormal things are for someone. Like you I would refuse to take medication for anything up until myeloma reared its head. Even now I do so.

My position is that without very aggressive advocacy for oneself with sympathetic clinicians, as you seem to have managed, most patients have little choice of the treatments they are given.
Like you I did not accept the 'plan' of the first myeloma doctor I saw. I knew the approach I felt might be better for me from all I had read, but of course in myeloma no one actually knows before treatment that this is a fact. I did get upfront what I wanted by seeing a 'top' doctor in the field. I do not know if I would have done better with the riskier first plan.

Myeloma is a field where the research is not in my opinion very joined up and drug company led. There are too many opinions on treatment without any real idea of what may work best with an individual patient in view of comprehensive individual health status, clonal heterogeneity, genetic make up and the changes in clones over time. It does make sense to replace the bone marrow as you did with a 'clean one'. But as Terrij states it is not an option offered at the outset to younger patients.

But, many patients want some certainty that a very aggressive approach at the outset will be significantly better than the current treatments with ongoing drug treatments, when some people live 7-8 years on these too nowadays.

I agree with you there has been a lot of 'hype' about novel drugs without recognition of their toxicities or failures to effect a really long term 'cure' for the majority. Maybe now when more initial regimes incorporate these we will see a change. But I do not know. I expected 2.5-4 years life expectancy after starting treatment more recently from all that I had read, based on older and newer data. If I get more then my doctors will have done better than average. I was not expecting a cure, as a once cancer researcher I have seen treatments improve, people live longer but cures remain rare.

I know young people in my clinic who had autos transplants as initial treatment choose not to have another transplant on relapse. This is what choice is about in each ones own particular life situation.

So my point is you are in your right to point to allo transplant as an option for younger people that they should discuss on diagnosis. But over stressing your own situation to state this as a curative option without serious risk is I feel is as wrong as doctors saying they can keep you going long on novel drugs without pointing to the serious toxicities which may affect your treatment. No one knows the outcome for any individual at the outset of even the best treatment.

Edna

[Terrij]

Re: Progress toward a multiple myeloma cure?

by Terrij on Mon Nov 09, 2015 10:14 am

Edna,

I agree with you also. The allo worked wonderfully for Mark. Would my daughter have had the same result? There is so much diversity in the disease and no physician can tell you what will work for sure. The patient does have to be a very strong advocate or have someone who will research options (that was me).

There is also so much diversity in doctor opinions of what is best. Some believe in transplant, some lean more towards new therapies. This makes it extremely difficult for the patient .

We were told at our daughter's diagnosis that it would probably be about 4 years to relapse after SCT and then she could have another SCT. Her stem cells are still frozen. It hasn't even been 4 years yet and she is gone. Not for lack of trying, she fought to the very end.

[ivanm]

Re: Progress toward a multiple myeloma cure?

by ivanm on Mon Nov 09, 2015 10:41 am

Mark's point, if I understand it correctly, has always been that allo is the only legitimate curative option right now for younger patients. The premise of his post was to highlight this for the benefit of younger readers who are new to the forum. Risk was nowhere a topic. It is implied that if one is interested in an allo, he/she will research the risk, which currently is not as high as it has been in the past.

While we have had disagreements with him on interpreting data, particularly regarding the plateauing and the 10-year overall survival, in substance I've always agreed with him.

Anyways, just one patient's view. Good luck to all.

[Edna]

Re: Progress toward a multiple myeloma cure?

by Edna on Mon Nov 09, 2015 10:55 am

Dear Terrij

You have been put in a situation that is upsetting to even consider looking back. I lost both most close family this year. My uncle only had cancer, lung, survived 7 years- his doctors were astounded. When my uncle tried to relate his situation to mine as was his want, he did not suffer any physical damage, I found this frustrating, trying to tell him I would be lucky to have so long, even though decades younger.

Hindsight also does not always offer an answer as to whether one took the best decision for oneself or not,. One never knows if the life expectancy was what would have been relevant to your specific situation or a specific result of a particular treatment. This especially when so much is unpredictable and doctors over emphasise the benefits of a treatment as if everyone gets the same outcome.

When I went to the 'top' doctor I asked how long do this doctors patients survive for. The first response was 10 years and then followed by, 'but not everyone does this'. An honest answer, highlighting uncertainty, even in a setting where the skills of the treating clinicians are high such that longer survival occurs.

So I understand the dismay and frustration with the journey your daughter experienced at such a young age.

With best wishes

Edna

[Edna]

Re: Progress toward a multiple myeloma cure?

by Edna on Mon Nov 09, 2015 11:01 am

Hi Ivanm

I would say an allo offers a potential for cure.

I think to say it is the only one offering a cure is not correct. I have met 20 year survivor of ASCT. I also have come across allo transplant patients of young age like Mark where they relapsed in a couple of years and are now fighting for survival.

Edna

[Terrij]

Re: Progress toward a multiple myeloma cure?

by Terrij on Mon Nov 09, 2015 11:13 am

This is the conundrum of myeloma. There is no definitive cure. An allo works for some, the measles therapy worked for 1 but not 12 others, T-cell therapy seems to have some cure for a few (it is to early to tell), tandem auto transplant works for some, drugs work better on some people than others. I hope some day there is a cure, but it is a very complicated disease.

I do agree with Mark that younger myeloma patients need to be more informed about options. This means that doctors need to have conversations about ALL the choices of treatments. We were told by a number of doctors that this is an older person's disease. Yes, that might be the majority, but just reading the Beacon you can see there are younger people. The choice for a younger person who up until the point of diagnosis was healthy and strong might be different than an older person. Personally, I feel there needs to be more discussion about younger patients.