[BallerinaBritt]

SCT timing for intermediate / higher-risk myeloma?

by BallerinaBritt on Tue Mar 17, 2015 4:50 pm

My Dad is 59 years old and has Stage 2, IgA kappa, t(4;14) multiple myeloma. He has no bone damage and no organ involvement. He is in the middle of his 6th cycle of Revlimid, Velcade, and dex (RVD), tolerating it very well, and has had nice results with blood tests showing no myeloma at this point. He is working full time and doing all the things he has always done. He feels good.

My Dad goes for pre-stem cell transplant (SCT) workups in 2 weeks, including a bone marrow biopsy (BMB). He can't decide whether to go through with the transplant in May or delay until time of progression. He must make his decision by April 10th. He did not have a gene array, so we don't know if his cancer is susceptible to melphalan. He will, however, collect for transplant in a month, no matter what he decides.

Can intermediate risk patients delay transplant if they are in complete remission, or should they?

Should he have Cytoxan (cyclophosphamide) or plerixafor (Mozobil) to prep for stem cell col­lec­tion?

Can someone help us find clarity?

[mrozdav]

Re: SCT timing for intermediate / higher-risk myeloma?

by mrozdav on Tue Mar 17, 2015 5:35 pm

Britt, can you explain what you mean by "gene array ... if his cancer is susceptible to mel­phalan"?

I, too, am t(4;14) IgA kappa and will start preparing for a SCT (Cytoxan will be used for mobili­za­tion) in a couple of weeks. I have been on Revlimid-dexamethasone (Rd) only and did not get Velcade as part of in­duction treatment. I am troubled about not having received Velcade because several forum participants have previously expressed strong opinions about the need for Velcade in the context of t(4;14).

I was in Stage I at time treatment commenced eight months ago and am currently at nCR. I will be quite interested in learning how your father fares as the whole process goes forward.

[BallerinaBritt]

Re: SCT timing for intermediate / higher-risk myeloma?

by BallerinaBritt on Tue Mar 17, 2015 6:32 pm

mrozdrav -

Some people's version of multiple myeloma will not respond to high dose melphalan and there are certain treatment centers using gene array analysis to identify these people. I'm sure you've read the stories of people who went through the ordeal of SCT and received no benefit. These are people who's cancer is not susceptible to melphalan.

I'm not sure how many treatment centers are using this now, or if it is just for patients in trials. Arkansas and Iowa are two places that do this. See the links below. It is done with a bone marrow sample that has a high enough percentage of cancer cells in which to analyse, so the newly diagnosed or relapsed I'm guessing.

I'm surprised you have not received Velcade as part of your induction. I would ask your doctor why. Maybe they are saving it for part of your SCT?

Arkansas gene array analysis information:
http://myeloma.uams.edu/researching-the-cure/gene-array-analysis/

University of Iowa gene array analysis information:
http://www.uihealthcare.org/content.aspx?id=228226

[Multibilly]

Re: SCT timing for intermediate / higher-risk myeloma?

by Multibilly on Wed Mar 18, 2015 8:33 am

Hi Britt,

I personally think the question of whether to delay or forgo transplant is not really tied to disease risk (this is my personal opinion, not a medical opinion). It's more of a fundamental question of just which route your dad wants to take.

In full disclosure, I am not a fan of auto transplants and would likely never consider one, regardless of my risk level. But, like your dad, I would do a harvest upfront just to cover my bases should I ever change my mind. I would also add that there is no right or wrong answer regarding upfront vs. delayed vs. no transplant (even when factoring in risk level), and each person needs to make their own decision as to what is the right path for them.

Also, bear in mind that there are currently studies under way that are attempting to better answer these kinds of questions (earlier studies focused on upfront vs delayed transplants had design flaws and/or were not utilizing the latest drug therapies that are currently available to multiple myeloma patients).

In the meantime, you might be interested in this study and note the excerpts below. For me, OS and not PFS is the key metric I am always concerned with in a study:

"Early Or Late Stem Cell Transplantation For Myeloma? New Study Finds Both Strategies Yield Similar Overall Survival," The Myeloma Beacon, Aug 16, 2013

"Results from a retrospective study show that delaying stem cell trans­plan­ta­tion following initial therapy may result in shorter progression-free survival following transplantation compared to transplantation soon after diagnosis.

However, the results also show that the timing of transplantation does not sig­nif­i­cantly impact overall survival ...

There was no significant difference in the share of patients in each group who had standard versus high-risk cytogenetics (chromosomal abnormalities). In both groups, about two thirds of the patients had standard-risk cytogenetics."

Regarding the use of Mozobil and the harvest procedure in general, see Andrew's 'Complete Guide to Stem Cell Collection' (Beacon forum, Jan 24, 2014).

Best of luck to you and your dad.

Last edited by Multibilly on Wed Mar 18, 2015 9:07 am, edited 2 times in total.

[Mark11]

Re: SCT timing for intermediate / higher-risk myeloma?

by Mark11 on Wed Mar 18, 2015 9:01 am

Hi Multibilly,

You wrote:

Also, bear in mind that there are currently studies under way that are attempting to better answer these kinds of questions (earlier studies focused on upfront vs delayed transplants had design flaws and/or were not utilizing the latest drug therapies that are currently available to multiple myeloma patients)."

What were the "design flaws" in those earlier studies? Could you show us some examples?

Patients that do autos can use the "latest drug therapies" as well. What study shows the "latest drug therapies" benefit patients that do not do autos more than those that do?

Peer reviewed studies are preferred over Youtube videos.

Mark

[Multibilly]

Re: SCT timing for intermediate / higher-risk myeloma?

by Multibilly on Wed Mar 18, 2015 11:47 am

Mark,

It’s generally accepted among myeloma specialists that, in the era of novel agents, it's not clear whether there is any OS benefit to early transplantation. This is a key motivator for the large, joint U.S. and French Phase 3 trial investigating the issue, and for another similar Phase 3 trial being carried out in Europe. If the question of early versus delayed transplant already had a definitive answer, then these trials would not currently be funded and underway.

It’s also true that several previous studies that have directly investigated early versus delayed single transplants were done prior to the novel therapy era. Other studies that have sought to address the issue have had flaws (including inconsistent maintenance therapies which were applied to the various cohorts, etc) , as mentioned by Dr. Ajay Nooka from Emory in this sum­mary of a retrospective study he and his colleagues did. Below is a short video summariz­ing what he presented at ASCO 2013.



There are also leading myeloma specialists who question the need for early transplantation as a universal strategy in the era of novel agents; see, for example, this abstract from the 2014 ASH meeting from Dr. Richardson, Dr. Anderson, and several other leading myeloma special­ists from Dana Farber:

PG Richardson et al, "Early or delayed transplantation for multiple myeloma in the era of novel therapy: does one size fit all?", ASH 2014 Education Book (link to abstract)

As a counterpoint, there is this (European) perspective by Drs. Moreau and Attal:

P Moreau & M Attal, "All transplantation-eligible patients with myeloma should receive ASCT in first response,"ASH 2014 Education Book (link to abstract)

In closing, I'm really not interested in getting into another debate with you on the subject of transplants. That subject has been covered in many earlier threads in this forum and includes a nice balance of differing and mutually-respected opinions from those in the Beacon community.

I would, instead, like to focus on helping out Britt by hopefully having other members of the Beacon community share their specific opinions in response to the question she has posed here. I look forward to hearing those other opinions.

[Mark11]

Re: SCT timing for intermediate / higher-risk myeloma?

by Mark11 on Wed Mar 18, 2015 12:59 pm

Hi Multibilly,

What makes you think I was l looking to debate upfront vs delayed auto?

I was hoping you could show me any of the "design flaws" in the studies that show doing a transplant (early or late) leads to greater Overall Survival than those that do not. It is generally accepted that patients that do autos have greater overall survival (early or delayed) than those that do not. I did not think there was any debate there. As Dr. Rajkumar wrote:

"Autologous stem cell transplantation is not curative in myeloma but prolongs overall survival."

("Maintenance Therapy in Multiple Myeloma", ASCO Post, May 2014 (link to article))

The Youtube video with Dr. Nooka discusses that his study was not randomized. There is no mention of any "design flaws" in other, older randomized studies with autos.

You never answered why new therapies would benefit patients who do not do autos (early or late) more than they would benefit those who do autos. That is the only way the argument that older studies that did not include novel agents would not matter due to new drugs being available. Dr. Richardson, Anderson, etc only discuss that all patients do not need to do early auto. I obviously agree with them, as I was not planning on doing an auto myself and all patients are different.

Why would I argue that all patients need an upfront auto if I was not planning on doing one myself?

In my opinion, the best way to help patients make decisions is to show links to peer reviewed papers and let them decide based on real data, not comments by people who are not a "fan of auto transplant" (whatever that means) and who have never used any myeloma therapy.

Mark

[mikeb]

Re: SCT timing for intermediate / higher-risk myeloma?

by mikeb on Wed Mar 18, 2015 1:54 pm

Hey Britt,

You sure opened a can of worms with your innocent first question, didn't you?

I'm not sure if you are new to the Forum or not, but in case you are new, I'll offer a little background commentary. Multibilly and Mark11 are both very knowledgeable (way more knowledgeable than I am!) and respected frequent contributors to the Forum. And, as you can see, they have different views on the cost / benefit tradeoffs of up-front auto SCTs, based on their reading of the literature and their experiences as members of this Forum community.

Both make valid points. Their different views reflect differences that some of the most respected myeloma researchers have right now.

I happen to be a participant in the joint US-French clinical trial that Multibilly mentioned. See the trial description at clinicaltrials.gov for details about the study.

I was randomized into the SCT arm of the trial. I began treatment in January 2013. At this point, I am still in the 2-year Revlimid maintenance phase of the trial. In July of last year, I reached stringent complete response (sCR) and minimal residual disease (MRD) negative status. Those are essentially the best responses you can get during treatment.

Of course, I am just one small data point in this large study. Interim results for the study have not been published yet. As you can imagine, I am eager to see what comes out of the study.

Early on during my treatment, the lead researcher for this study at my myeloma center told me that he thinks that in 10 years (which would be 8 years from now), it will be unusual to see SCTs used in multiple myeloma. Novel agents will be so effective that we won't need to use SCTs with their additional risks and potential side effects.

But right now we are in a transition phase where some people think today's novel agents are all we need up front, and some think there is still a benefit to the upfront SCT. The study I'm in will give some answers to that question, using today's novel agents. As new novel agents are developed, more studies like the one I'm in will need to be done with those agents. The needle keeps moving, which is great for us patients.

So, the bottom line is that I don't think your father's decision whether to do the upfront SCT is a clear cut choice either way. I think it is important for him to talk in detail with his myeloma special­ist about the pros and cons of the SCT, and perhaps to get second or third opinions. And it's important for you (and your father, if he is up to it) to educate yourselves as much as you can about the pros and cons. Multibilly and Mark11 have given you some good resources to check out. Also, you'll find lots of information about SCTs by searching for that topic in the Forum here.

On your second question - that's a bit easier. Multibilly gave you a link to a great thread with details about stem cell mobilization and collection. I was given Cytoxan to start off my stem cell mobilization, and then I gave myself Neupogen injections for 10 days. I expect your dad's myeloma center will have their own process for doing things.

Best wishes to your father, whatever he decides to do. Please keep us posted on how things go for him.

Mike

[Multibilly]

Re: SCT timing for intermediate / higher-risk myeloma?

by Multibilly on Wed Mar 18, 2015 2:49 pm

Nice follow-up Mike. I didn't realize that you were personally involved in the US-French study. I learn something new everyday and always appreciate your perspectives.

Britt, I would underscore Mike's suggestion to discuss all this at length with your Dad's spe­cial­ist(s), including a second opinion or two. The specialists are the ones that are best equipped to answer these questions since they've lived these situations many a time with their own patients.

Take care all.

[DanielR]

Re: SCT timing for intermediate / higher-risk myeloma?

by DanielR on Wed Mar 18, 2015 3:42 pm

Britt

I had a SCT in June of 2013. At the time, I was just extremely grateful just to be alive. My on­col­o­gist doesn't really use the staging method, but when I later asked him about it, he said that, if he had, I would have been at the very top of the scale. In January of that year, neither he nor any of my other doctors had expected me to survive. 

Because my initial diagnosis had been so dire (del(17p), IgG kappa light chain, many lytic lesions, 12% healthy plasma cells [yes, 88% myeloma cells], and immobilized by pain and weakness), I didn't feel like I had an option whether to consider choosing a SCT or not. As others have mentioned, everyone responds differently to the transplant process. It was a very unpleasant ordeal for me.

On the other hand, I got a VGPR from the transplant, and that improved to a CR within 6 months of follow-up treatments with Velcade and dex. Today, about 21 months post transplant, I have been off all myeloma meds for 1 year with no M-spike measurable, I am totally mobile, and only experience pain slightly more than what might normally be expected for someone my age. 

Despite these obvious positives, I am also plagued with extreme energy depletion. No one knows why this is, but everyone kind of assumes it is at least partially a by-product of the trans­plant process. I have been on disability since January of 2013, and it doesn't look like I will ever be able to work again.

As to your father's decision, if I were in his place, with his particular set of symptomologies, I would forego, or at the very least, postpone a SCT for as long as possible. I base this in part on my experience with the SCT, but also, as far as my personal research, combined with dis­cus­sions with my oncologist, indicates, longevity is about the same with or without the transplant. While I'm not willing to engage in the arguments currently evoked by your question, I will say that Dr. Berenson's work is very persuasive to me. In a nutshell, here's his perspective:

“The treatment of multiple myeloma is no longer a 100-yard dash; it is a marathon,” said James R. Berenson, MD, the medical and scientific director of the Institute for Myeloma and Bone Cancer Research in West Hollywood, Calif. According to Dr. Berenson, better-tolerated, newer drug therapies now produce response rates that rival those produced with SCT, while preserving future options when the cancer progresses."

Source: "Experts Disagree on Role of Transplant in Myeloma," Clinical Oncology News, August 2013 (link to full text of article)

Britt, you also posed the following question: "Should he have Cytoxan (cyclophosphamide) or plerixafor (Mozobil) to prep for stem cell col­lec­tion?" I had my SCT, as well as the collection process, done at City of Hope in Duarte, CA, and they used both Cytoxan and Mozobil. So, again, I was spared any decision making on that front.

Here's wishing you and your father all the best

Aloha
Daniel