[MJB]

Auto-allo strategy for high-risk multiple myeloma?

by MJB on Thu Mar 19, 2015 6:58 pm

I've been lurking in this forum ever since my diagnosis, and it has really helped me to under­stand a lot of things about my disease, and I hope to learn much more in the coming days.

I'd like to get some advice, and please forgive me if I use the wrong terminology – I'm still learning.

I was diagnosed with multiple myeloma in September 2014 and started treatment with Velcade / dex one month later. I am scheduled to do an autologous stem cell transplant (SCT) at Mayo Clinic (Scottsdale, AZ) in a month. I have the "high-risk del(17p) cytogenetics".

The Velcade / dex seems to be working well for now. My kappa free light chains have dropped from 400 (mg/dL) to 5.7 (normal 1.9), which puts me in VGPR, I believe. I have never had an M-spike, as I seem to have the multiple myeloma type where that is not produced. The hope seems to be that I will achieve CR sometime near or after the transplant.

I have been reading a lot of information on the Internet related to my particular version of multiple myeloma and it seems that I might be a candidate for the auto / allo tandem transplant advocated by many doctors / centers. Of particular interest is a John Theurer Cancer Center stud that claims to have a good success rate with this approach, especially if done early in disease course (consolidation vs salvage), as was mentioned earlier in this forum thread:

"Results of allo transplant study at John Theurer Center," forum disc. started Oct 23, 2014

I have also read on this forum about people undergoing allos, and the chances of dying from transplant-related mortality seems to be decreasing in recent years (maybe from 30% to 10-20%, at least that's the sense I get from the excellent postings by Mark11 in the forum thread "Allo transplantation - what are your thoughts" (started Sep 30, 2014).

My doctor at Mayo is very much against the allo transplant. He says that 30% death from transplant is more accurate, with only 10% chance of cure. Of course, since we all know that the disease will relapse, I'm going to die anyway, so I may be willing to accept the risk of dying earlier and get the allo.

My stats:

• 51 years old (apparently considered young for this disease)
• No "comorbidities" (other than being an overweight guy)
• High-risk del(17p) disease with strong likelihood of early relapse
• Currently in VGPR, hoping to get to CR soon
• Auto transplant scheduled next month
• Probably maintenance afterward, perhaps with Velcade, Revlimid, and dex (VRD), which has shown good results in high-risk disease.

My questions:

1. What is everyone's opinion about the tandem auto / allo for a person like me? I'd really like to hear from others who have done the tandem auto / allo and how it has worked out for them with issues like GVHD and AVHD issues.
2. Has anyone done the auto / mini allo? I'm actually not sure if mini allos are the reason that the success rate for the allo has improved recently. Is that the reason? It seems that GVHD is actually desirable with the mini allo, as it helps to control the disease.
3. Other than John Theuer Cancer Center (responsible for study above), has anyone done the tandem at a different hospital? If so what was your experience? Can anyone recommend a hospital with a good success rate in doing these procedures?

Thanks for your replies,

MJB

[mikeb]

Re: Auto-allo strategy for high-risk multiple myeloma?

by mikeb on Fri Mar 20, 2015 11:15 am

Hi MJB,

(I have the same initials!)

You're asking some very good questions. I am not an expert on allo transplants by any means, so I'm not going to get into a debate about whether that's the right way to go or not. I just want to try to answer your questions directly based on what I do know and offer some "non-denomi­na­tional" advice. And, with that approach, your third question is really the only one I can give you input on.

At John Theurer, another doctor you might consider is Dr. David Vesole. I heard him speak at a conference in Oct 2014 regarding their transplant research.

Also, there have been at least a couple of threads in this Forum discussing tandem auto-allo transplants. In both cases, they were to be performed at Fred Hutchinson in Seattle. In the most recent thread (from 2014), the patient was being treated by Dr. Edward Libby, who is a con­trib­utor to this Forum. I think that auto-allo was part of a clinical trial. More details are avail­able in this thread,

"Starting tandem auto-allo transplants," forum disc. started Dec 17, 2014

An older thread (from 2010) also discussed tandem auto-allo transplants:

"Auto Allo Tandem Transplants," forum disc. started Apr 12, 2010

Dr. William Bensinger from Fred Hutchinson was a participant in that thread. I apologize if you've already seen these threads, but just wanted to make sure you were aware of them.

As you may know, the University of Arkansas Medical Sciences (UAMS) team, until recently led by Dr. Bart Barlogie, has done a lot of research into the use of tandem transplants. I think they are more focused on tandem auto-auto transplants, but I think they have also done auto-allo tandems.

If you are seriously considering tandem auto-allo transplants, I suggest that you contact doctors at one (or even better, two) of these places and talk directly with them about your specific case and the pros and cons of a tandem auto-allo for you. That's really the only way to know if this path is something you should try.

Best wishes to you - glad to hear that the Velcade / dex has been working well for you. Please keep us posted on what you decide and on how things progress.

Mike

[CindyBrown]

Re: Auto-allo strategy for high-risk multiple myeloma?

by CindyBrown on Fri Mar 20, 2015 8:37 pm

MJB,

I am undergoing a tandem auto-allo. My auto was February 9 and my allo will be April 14. I am treating at Fred Hutchinson / Seattle Cancer Care Alliance. I am planning to blog my allo since no one has done that (at least not recently). I was told about 10-15% mortality, 15% rate, and 50% chance of longer progression-free survival. I am okay with those odds based on how aggressive my cancer has been and the number of drugs I had to use to get even close to be well enough to do the auto.

Feel free to ask me questions if you would like

Cindy

[Mark11]

Re: Auto-allo strategy for high-risk multiple myeloma?

by Mark11 on Sat Mar 21, 2015 10:09 am

Hi MJB,

Thanks for the compliment - sounds like you have a great knowledge of myeloma therapy.

With respect to how allos work for patients with 17P13, it seems to come down to what your re­mission status is after you complete your therapy. If you get sustained MRD negative status, the chance of long term remission/cure seems high.

"The 5-year progression-free survival differed substantially accord­ing to the achieved remission: 17% for partial remission, 41% for CR, 57% for mCR, and 85% for sus­tained mCR. These results suggest that auto-allo tandem SCT may overcome the negative prog­nostic effect of del(17p13) and/or t(4;14) and that achieve­ment of molecular remission resulted in long-term freedom from disease." [1]

With respect to question 2, I will give you my opinion on why the success rate has risen in re­cent years. It actually has little to do with changes in the allo transplant procedure. There have been great strides in supportive care and in preventing / controlling GVHD, but the effective­ness of the procedure itself may have remained basically the same for 3 decades plus.

The main thing to remember is that what is most important to making an allo transplant suc­cess­ful is being in first complete response when you do the procedure. Let me show you 3 quick studies to show why I think this. These are not studies on myeloma patients, but the prin­ciple is the same for myeloma patients.

This describes Dr. E. Donnall Thomas first success with allo transplant.

In 1977, the Seattle group reported 100 transplantations, with chemotherapy and radiation therapy in 54 patients with acute myeloid leukemia (AML) and in 46 patients with acute lymphoblastic leukemia (ALL). Only 13 patients were alive without disease 1–4.5 years after HSCT.14 However, this small cure rate only encouraged Thomas to try and apply allo­geneic HSCT earlier in the course of acute leukemia, and in 1979 he reported a cure rate of 50% in AML patients transplanted in first remission.15 Perhaps the most important thing Thomas found in his work was the power of the immune system to eradicate cancer. In 1990, E. Donnall Thomas won a Nobel Prize for his discoveries in cell transplantation in the treatment of human disease. " [2]

Note the cure rate is only 13% in relapsed patients. This is why you will hear doctors state that im­muno­therapy works best in patients with low tumor burden. First CR is the lowest tumor bur­den a blood cancer patient will have.

Move forward 3 decades (2007) and you see this statistic,

Stem-cell transplantation from allogeneic donors may be curative for 10–20% of patients with chemotherapy-resistant, refractory hematologic malignancies, and for up to 80% of patients who are transplanted in remission. Much of the high response and curative potential of allografts is attributed to a ‘graft-versus-tumor’ effect." [3]

Note the cure rate for relapsed patients did not rise for 3 decades, but the cure rate for the first com­plete response group rises. In my opinion, this study from 2014 on high-risk blood cancer patients is an example of a study that tells us why.

With a median follow-up period of 2.2 years, the 2-year disease-free survival (DFS) and overall survival (OS) rates were 62% and 67%, respectively. Donor relatedness did not affect NRM, DFS, or OS. Patients in complete remission (CR) without evidence of minimal residual disease (MRD) had markedly better DFS (80%) and OS (80%) than patients in CR with MRD or with active disease at the time of transplantation (DFS, P = .0005; OS, P = .019)." [4]

In my opinion, it really is not the allo transplant procedure itself as much as it is having good therapies to get you to a deep remission prior to the transplant. I give Velcade a lot of credit for my successful allo, even though I had not used Velcade for 5 months before my allo because Velcade played a big role in my being in CR prior to my allo. Therapies are not competing with each other - they complement each other.

With respect to where you do it and how you do it, IMO a patient should get multiple opinions (if possible) with respect to how to do the transplant and go with the one they are most com­fort­able with. Like all aspects of myeloma therapy, there is no right or wrong way to do an allo. Dif­fer­ent methods have different benefits and risks.

For example, Beacon Medical Advisor Dr. Landau at Memorial Sloan-Kettering is part of a study where the risk of extensive chronic GVHD is basically zero, but you do have to use higher doses of chemotherapy than someone that does a "mini" allo. Other methods can use minimal chemotherapy but have higher risk of extensive chronic GVHD.

I hope that helps and good luck moving forward.

Mark

References:

[1] N Kroeger et al, "Impact of high-risk cytogenetics and achievement of molecular remission on long-term freedom from disease after autologous-allogeneic tandem transplantation in patients with multiple myeloma," Biology of Blood and Bone Marrow Transplantation, March 2013 (link to article abstract)

[2] I Henig & T Zuckerman, "Hematopoietic Stem Cell Transplantation—50 Years of Evolution and Future Perspectives," Rambam Maimonides Medical Journal, October 2014 (link to full text of article at PubMed)

[3] WI Bensinger, "Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?," Best Practice & Research Clinical Oncology, December, 2007 (link to full text of article at PubMed)

[4] CG Kanakry et al, "Multi-institutional study of post-transplantation cyclo­phos­pha­mide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow trans­plantation using myeloablative busulfan and fludarabine conditioning," Journal of Clinical Oncology, November 2014 (link to article abstract)

[JBenton9758]

Re: Auto-allo strategy for high-risk multiple myeloma?

by JBenton9758 on Tue Mar 24, 2015 10:38 pm

I considered the transplant route when I was diagnosed. But when I looked at all the data, it be­came apparent that using the one with your own stem cells "does not cure your multiple myeloma." The reason is very simple, in that the problem lies with your stem cells in the first place. Using the other one that requires a matching bone marrow donor is still too dangerous. Going with around a 15% mortality rate might sound great, unless you're one of those 15%. Then the other com­pli­ca­tions that you probably will have to live with just didn't seem worth it to me.

I got the party line from the doctors, but when you really push them they will admit that the results obtained from using your own stem cells are no better than some of the other better treatments that are out there. I had three of the top specialists in Georgia admit to me that they could not disagree with my decision NOT to have a transplant. And that was after they hyped it up for months before that. If you look for them, there are meta studies out there that say the same thing ... that stem cell transplants are not the answer to this deadly cancer.

The best strategy I see is to use the best chemo out there to stay alive until they can find something that IS A CURE!

I wish anyone who does go this route the very best. But it just wasn't for me!

[Mark11]

Re: Auto-allo strategy for high-risk multiple myeloma?

by Mark11 on Wed Mar 25, 2015 7:29 am

Hi JBenton9758,

"Using the other one that requires a matching bone marrow donor is still too dangerous. Going with around a 15% mortality rate might sound great, unless you're one of those 15%. Then the other com­pli­ca­tions that you probably will have to live with just didn't seem worth it to me."

That is your opinion and it is great that you came on to express it. It is also true that 10% of all myeloma patients die during the first year after diagnosis.

"Early Mortality Rates

Over the entire course of the study, 13 percent of the patients died within the first year of diagnosis. However, the one-year mortality rate significantly decreased during the study, from 16 percent for patients diag­nosed between 2001 and 2005, to 10 percent for patients diag­nosed between 2006 and 2010.

Patients who received one or more novel agents as part of their initial therapy had lower early mortality com­pared to those who did not (8 percent versus 19 percent, respectively)."
https://myelomabeacon.org/news/2013/11/01/multiple-myeloma-survival-significantly-increases-last-decade/

No matter what therapy route a myeloma patient chooses they are at risk of early mortality.

I would also point out that long term survivors allo transplant can have quality of life on par with the general population. I have never seen any peer reviewed study that shows patients on never ending cycles of novel agents having QOL on par with the general population.

"This study reveals that three or more years following HSCT, physical health, mental health
and HRQL have generally recovered to normative values and that these trajectories remain
stable. This observation that self-assessed health status and HRQL are preserved three or
more years post-transplant supports previous studies suggesting that a full recovery is likely
by three years post-transplant [39]. The novel insight provided by this study is that the
trajectory remains stable, suggesting that treatment with allogeneic HSCT, while expensive,
potentially risky, and burdensome, has the potential to return survivors to a health state that
is comparable to healthy population values."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962950/pdf/nihms550392.pdf

"Most survivors beyond 5 years had an excellent performance status with no difference in physical and mental health and higher HRQL scores (P = .02) compared with population norms. Although physical and psychologic symptom distress was low, those with higher symptom distress experienced inferior HRQL. These results show that 5 or more years after T cell-depleted HSCT for hematologic malignancy most individuals survive disease free with an excellent performance status, preserved physical and psychological health, and excellent HRQL."
http://www.ncbi.nlm.nih.gov/pubmed/20302959

Curative therapy and the potential to have quality of life on par with the general population sounds a whole lot more appealing to me than:
"The best strategy I see is to use the best chemo out there to stay alive until they can find something that IS A CURE!"

Mark

[Spirit]

Re: Auto-allo strategy for high-risk multiple myeloma?

by Spirit on Wed Mar 25, 2015 11:31 am

Mark11,

I am new to the Beacon. Could you explain what made you choose the allo transplant over the auto transplant? When was this transplant done and how are you feeling now?

Thx!