My husband (17p53-) is 3 years post auto-transplant. Other than myeloma (!), he is in good health. He has been on treatment since his transplant (Revlimid, then Revlimid, Velcade, and dexamethasone), but it is no longer working and his m-spike is at 3 g/dL (from 0.1, no other symptoms).
They are now switching his treatment to Kyprolis (carfilzomib), Pomalyst (pomalidomide), and Revlimid. This plan just came via email from his transplant doctor, to be carried out by his local oncologist. My husband will be traveling to see his transplant doctor (6 hrs away) in 1 month. I'm sure things will be discussed in details at that time. More labs and a skeletal series are planned before that visit.
My question is: He has plenty more cells on ice for another transplant. Is that not really "in vogue" to do at relapse anymore? Are the new drugs the new standard of care?
Thanks.
Forums
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rumnting - Who do you know with myeloma?: husband
- When were you/they diagnosed?: 4/9/11
- Age at diagnosis: 54
Re: Another transplant at relapse - is it out of favor?
I would love to hear some responses to this. Our daughter age 35 was diagnosed in January 2012. She did Velcade and dex and after 4 cycles was in CR. She did a SCT and reached CR after completing. She followed with 16 months of Revlimid 5 mg. She began to relapse and they upped it to 10 mg but it didn't do anything.
Now she has started Kyprolis and dex. If this works, I'm thinking staying on a med regimen might be better than another transplant, since it didn't work that long. They had collected enough cells for 2 transplants.
Now she has started Kyprolis and dex. If this works, I'm thinking staying on a med regimen might be better than another transplant, since it didn't work that long. They had collected enough cells for 2 transplants.
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TJ13
Re: Another transplant at relapse - is it out of favor?
I haven't started treatment yet for my relapse, but the plan (eventually) is chemo induction (including Revlimid, since I have not taken it yet) and then followed by another transplant.
I live in Canada, so transplants are still done here routinely. We don't have access to as many drugs / trials etc as our neighbours to the south. The rule is if you had at least two years remission from transplant the first time around, they will do a second one.
I live in Canada, so transplants are still done here routinely. We don't have access to as many drugs / trials etc as our neighbours to the south. The rule is if you had at least two years remission from transplant the first time around, they will do a second one.
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lys2012 - Name: Alyssa
- When were you/they diagnosed?: 2010, Toronto, Canada
- Age at diagnosis: 32
Re: Another transplant at relapse - is it out of favor?
Hi Rumnting,
Good luck to your husband with his new treatment.
My general comment to patients with respect to doing a 2nd auto transplant is that if you are going to do one, you should look into a clinical trial and not just do another one with only high dose melphalan for conditioning.
Of all the things I am most surprised about myeloma therapy in 2014, it is that the doctors have not improved the conditioning prior to an auto. I would ask about a combination of alkylators along with a proteasome inhibitor or adding some type of experimental immunotherapy. I have benefited greatly from high dose chemotherapy combined with immunotherapy, so anything that tries to copy an allogeneic transplant is worth a try IMO.
Do not forget an auto is just a high dose of an alkylating agent. You could ask your doctor about adding an alkylator to the Kyprolis, like Cytoxan or Treanda, and try to avoid using an IMID at this time. If a monoclonal antibody (elotuzumab or daratumamab) gets approved, they tend to combine well with an IMID. Less IMID resistance could help your husband respond better when combining an IMID with a monoclonal antibody in the future.
I also would not forget about trying an anthracycline (Doxil, doxorubicin). I responded very well to Velcade / Doxil / dex for my induction. In my opinion, one of the biggest mistakes doctors / patients make in 2014 is not trying to combine older drugs with the new ones. If you read some of Dr. Goodman's columns, note that he responded well to older combos like DCEP. DCEP is dex, Cytoxan, etoposide (topoisomerase inhibitor), and cisplatin (platinum drug). Those drugs are in VTD-PACE as well.
As you can see, I like hitting the disease from multiple pathways in a short period of time as opposed to just keep using the same drugs (IMIDs and proteasome inhibitors) over and over again.
Mark
Good luck to your husband with his new treatment.
My general comment to patients with respect to doing a 2nd auto transplant is that if you are going to do one, you should look into a clinical trial and not just do another one with only high dose melphalan for conditioning.
Of all the things I am most surprised about myeloma therapy in 2014, it is that the doctors have not improved the conditioning prior to an auto. I would ask about a combination of alkylators along with a proteasome inhibitor or adding some type of experimental immunotherapy. I have benefited greatly from high dose chemotherapy combined with immunotherapy, so anything that tries to copy an allogeneic transplant is worth a try IMO.
Do not forget an auto is just a high dose of an alkylating agent. You could ask your doctor about adding an alkylator to the Kyprolis, like Cytoxan or Treanda, and try to avoid using an IMID at this time. If a monoclonal antibody (elotuzumab or daratumamab) gets approved, they tend to combine well with an IMID. Less IMID resistance could help your husband respond better when combining an IMID with a monoclonal antibody in the future.
I also would not forget about trying an anthracycline (Doxil, doxorubicin). I responded very well to Velcade / Doxil / dex for my induction. In my opinion, one of the biggest mistakes doctors / patients make in 2014 is not trying to combine older drugs with the new ones. If you read some of Dr. Goodman's columns, note that he responded well to older combos like DCEP. DCEP is dex, Cytoxan, etoposide (topoisomerase inhibitor), and cisplatin (platinum drug). Those drugs are in VTD-PACE as well.
As you can see, I like hitting the disease from multiple pathways in a short period of time as opposed to just keep using the same drugs (IMIDs and proteasome inhibitors) over and over again.
Mark
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Mark11
Re: Another transplant at relapse - is it out of favor?
Hi Rumnting,
I am sorry to hear of your husband's progression, but I have good hope he will respond to the combination of Kyprolis, Pomalyst and likely dex (rather than Revlimid?).
As for the second auto stem cell transplant, there certainly can be value, especially if
1) He went into remission after his first transplant, and
2) He is responding to his current chemotherapy (i.e., his is not refractory).
Lastly, patients who benefit most from a second transplant are those who remained in remission for some time after the first, although the exact duration has varied among studies, ranging from 12 months to 36 months.
In general, I think most experts agree that a patient who had a remission for more than 18 months is a reasonable candidate for a second transplant, especially, as Mark suggests, with novel (or combination) conditioning regimens. High dose melphalan and Velcade has been studied, and we are currently studying Kyprolis in combination with melphalan as conditioning.
Yet, as Mark also suggested, transplant for the most part is just a way to deliver high dose melphalan (or, in other words, is another line of chemotherapy). As such, whether a second transplant is more effective than combinations of newer drugs is not known, but is currently being studied (we have a trial at Memorial Sloan-Kettering, and a national study is planned). The only caveat to that is that, with transplant, we do see some resetting of your own immune system, which also helps fight against cancer.
I think the bottom line for any individual patient is that the decision to transplant or use newer combinations has to be a thoughtful one. It should be a joint conversation between your husband, yourself, the primary oncologist and the transplant physician. Factors to be considered include prior response, tolerance, clinical trial options (as Mark also suggested, new, exciting, and potentially very effective immunotherapeutic options are being investigated), stem cell availability as well as donor availability (which could also be considered moving forward).
I am hopeful that he has several options currently and, hopefully, even more moving forward.
Hope that helps!
I am sorry to hear of your husband's progression, but I have good hope he will respond to the combination of Kyprolis, Pomalyst and likely dex (rather than Revlimid?).
As for the second auto stem cell transplant, there certainly can be value, especially if
1) He went into remission after his first transplant, and
2) He is responding to his current chemotherapy (i.e., his is not refractory).
Lastly, patients who benefit most from a second transplant are those who remained in remission for some time after the first, although the exact duration has varied among studies, ranging from 12 months to 36 months.
In general, I think most experts agree that a patient who had a remission for more than 18 months is a reasonable candidate for a second transplant, especially, as Mark suggests, with novel (or combination) conditioning regimens. High dose melphalan and Velcade has been studied, and we are currently studying Kyprolis in combination with melphalan as conditioning.
Yet, as Mark also suggested, transplant for the most part is just a way to deliver high dose melphalan (or, in other words, is another line of chemotherapy). As such, whether a second transplant is more effective than combinations of newer drugs is not known, but is currently being studied (we have a trial at Memorial Sloan-Kettering, and a national study is planned). The only caveat to that is that, with transplant, we do see some resetting of your own immune system, which also helps fight against cancer.
I think the bottom line for any individual patient is that the decision to transplant or use newer combinations has to be a thoughtful one. It should be a joint conversation between your husband, yourself, the primary oncologist and the transplant physician. Factors to be considered include prior response, tolerance, clinical trial options (as Mark also suggested, new, exciting, and potentially very effective immunotherapeutic options are being investigated), stem cell availability as well as donor availability (which could also be considered moving forward).
I am hopeful that he has several options currently and, hopefully, even more moving forward.
Hope that helps!
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Dr. Heather Landau - Name: Heather Landau, M.D.
Beacon Medical Advisor
Re: Another transplant at relapse - is it out of favor?
Thank you, Dr. Landau.
Your answer was very informative and gave us some things to specifically be thinking about (questions) before his visit at Mayo next month.
Your answer was very informative and gave us some things to specifically be thinking about (questions) before his visit at Mayo next month.
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rumnting - Who do you know with myeloma?: husband
- When were you/they diagnosed?: 4/9/11
- Age at diagnosis: 54
Re: Another transplant at relapse - is it out of favor?
Oops - yes, dex, not Revlimid.
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rumnting - Who do you know with myeloma?: husband
- When were you/they diagnosed?: 4/9/11
- Age at diagnosis: 54
Re: Another transplant at relapse - is it out of favor?
I was diagnosed with multiple myeloma in July 2006 at age 31. After several rounds of Velcade, thalidomide, and dex, I had a transplant in February 2007. I was in remission (drug free) for over two years before my M-spike slowing started climbing. I went on low dose Revlimid and dex for several months before having another transplant in February 2011. My M-spike when I had the transplant was only at 0.5 g/dL.
Some would've said I should've waited to see if chemo could've taken care of it. But my first transplant went smoothly - I was only admitted to the hospital when I got melphalan, and the rest was outpatient. I was back to work part time in about a month, full time in two months. I decided on another one early because it worked well the first time.
Again, the transplant went smoothly and I was back to work part time in about 6 weeks. I stayed on Revlimid maintenance for about a year, then told my oncologist that I wanted a break. I have been in remission and drug free since then.
For me, the second transplant was completely worth it.
Some would've said I should've waited to see if chemo could've taken care of it. But my first transplant went smoothly - I was only admitted to the hospital when I got melphalan, and the rest was outpatient. I was back to work part time in about a month, full time in two months. I decided on another one early because it worked well the first time.
Again, the transplant went smoothly and I was back to work part time in about 6 weeks. I stayed on Revlimid maintenance for about a year, then told my oncologist that I wanted a break. I have been in remission and drug free since then.
For me, the second transplant was completely worth it.
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jennifrp - Name: Jen
- Who do you know with myeloma?: me
- When were you/they diagnosed?: 2006
- Age at diagnosis: 31
Re: Another transplant at relapse - is it out of favor?
Mark,
I tend to agree with most of your comments and I think this is great advice.
I think a lot of folks do lose sight of the fact that the high dose therapy portion of an auto transplant IS the treatment itself. It is also rather remarkable that there haven't been advances beyond the standard ASCT conditioning regimen of melphalan.
I would also give serious consideration to the combo of Velcade, Doxil and dex (aka PAD or VDd). This is a combo I would likely gravitate towards if and when I do induction (Dr. Berenson is a fan of combining the old with the new, and this was one of the combos he would likely recommend to me, should I progress from smoldering myeloma). But this is based on my particular situation and current cytogenetics.
I tend to agree with most of your comments and I think this is great advice.
I think a lot of folks do lose sight of the fact that the high dose therapy portion of an auto transplant IS the treatment itself. It is also rather remarkable that there haven't been advances beyond the standard ASCT conditioning regimen of melphalan.
I would also give serious consideration to the combo of Velcade, Doxil and dex (aka PAD or VDd). This is a combo I would likely gravitate towards if and when I do induction (Dr. Berenson is a fan of combining the old with the new, and this was one of the combos he would likely recommend to me, should I progress from smoldering myeloma). But this is based on my particular situation and current cytogenetics.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Another transplant at relapse - is it out of favor?
Hi Multibilly,
It will be 4 years since my diagnosis next week. Believe it or not, even after the studies / approval of carfilzomib [Kyprolis] and pomalidomide [Pomalyst] in the last the 4 years, I still think Velcade / Doxil / dex is a great choice of induction for younger myeloma patients if they are planning to auto transplant or not. If going to transplant, it spares the patient of exposure to alkylators prior to transplant.
In the non-transplant setting, it could work and get the patient to remission and make it so the patient does not start exposure/resistance to both IMIDs and proteasome inhibitors as soon as they start treating.
As I have mentioned in other threads, I would not be inclined to use an IMID and proteasome inhibitor during induction, as the prognosis is currently poor for patients that are not responding to those 2 classes of drugs. I have also mentioned that one of the things that gives me great peace of mind is knowing what my next line of therapy will be. I have never used any IMID, so Revlimid should be effective for me as Revlimid is thought to have synergy with a donor immune system.
You wrote: "Dr. Berenson is a fan of combining the old with the new, and this was one of the combos he would likely recommend to me, should I progress from smoldering myeloma."
I have put this link up many times but I will put it up one more time, as I agree with Dr. Berenson 100% on this point.
S Eshaghian and JR Berenson, "Multiple myeloma: improved outcomes with new therapeutic approaches," Current Opinion in Supportive & Palliative Care, September 2012 - Volume 6 - Issue 3 - p 330–336
Excerpt from abstract:
"Most patients with multiple myeloma in both the frontline and relapsed/refractory settings are now treated with a combination of dexamethasone with the proteasome inhibitor bortezomib and/or an immunomodulatory agent thalidomide or lenalidomide. However, alkylating agents including melphalan, cyclophosphamide and most recently bendamustine as well as anthracyclines, especially the pegylated liposomal doxorubicin, have shown high response rates and prolonged remissions when combined with these agents."
Mark
It will be 4 years since my diagnosis next week. Believe it or not, even after the studies / approval of carfilzomib [Kyprolis] and pomalidomide [Pomalyst] in the last the 4 years, I still think Velcade / Doxil / dex is a great choice of induction for younger myeloma patients if they are planning to auto transplant or not. If going to transplant, it spares the patient of exposure to alkylators prior to transplant.
In the non-transplant setting, it could work and get the patient to remission and make it so the patient does not start exposure/resistance to both IMIDs and proteasome inhibitors as soon as they start treating.
As I have mentioned in other threads, I would not be inclined to use an IMID and proteasome inhibitor during induction, as the prognosis is currently poor for patients that are not responding to those 2 classes of drugs. I have also mentioned that one of the things that gives me great peace of mind is knowing what my next line of therapy will be. I have never used any IMID, so Revlimid should be effective for me as Revlimid is thought to have synergy with a donor immune system.
You wrote: "Dr. Berenson is a fan of combining the old with the new, and this was one of the combos he would likely recommend to me, should I progress from smoldering myeloma."
I have put this link up many times but I will put it up one more time, as I agree with Dr. Berenson 100% on this point.
S Eshaghian and JR Berenson, "Multiple myeloma: improved outcomes with new therapeutic approaches," Current Opinion in Supportive & Palliative Care, September 2012 - Volume 6 - Issue 3 - p 330–336
Excerpt from abstract:
"Most patients with multiple myeloma in both the frontline and relapsed/refractory settings are now treated with a combination of dexamethasone with the proteasome inhibitor bortezomib and/or an immunomodulatory agent thalidomide or lenalidomide. However, alkylating agents including melphalan, cyclophosphamide and most recently bendamustine as well as anthracyclines, especially the pegylated liposomal doxorubicin, have shown high response rates and prolonged remissions when combined with these agents."
Mark
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Mark11
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