My multiple myeloma Story so far
I was diagnosed in Jan 2005 at age 60. At that time, I had very high protein count and lesions on my spine, as well as a major lesion on my hip and collarbone. Estimated as stage 2 or 3 with an overall prognosis of five years.
As a Kaiser patient, I’m fully covered, so we began induction therapy with Dex, Thalidomide, and three treatments of Fosamax. I responded well, and in a few months we harvested stem cells for a SCT.
Kaiser does transplants in a partnership with City of Hope (COH), which has a dedicated hospital for transplants only.
Meanwhile, it was determined that my 63-yr old sister was a match for an allo-transplant, which COH was doing in clinical trials.
My Kaiser Hematologist was ambivalent about the allo-transplant. The City of Hope people were not. They were advocating the allo-transplant strongly and even using the word “cure”. I tried getting as much information as I could about allo-transplants, but there was almost none I could find about survival rates, cures, or overall efficacy of the treatment. The information seemed to be locked up within the clinical trials. There was information about allo-transplant mortality rates (30%) and the high possibility of HVGD and it’s associated maladies.
Confused, I consulted with Dr.Berenson, a prominent multiple myeloma doctor and anti-transplant advocate from Cedars-Sinai Hospital. His negative experiences in his practice with allo-transplant survivors convinced me to not do the allo-transplant……however, he admitted that I might benefit from a auto-transplant, based mainly on the advanced state of my disease.
Based on the above information, I decided on the auto-transplant.
I had a successful SCT at COH In September of 2005, achieving a CR with the single transplant (they were considering a tandem SCT, but after the CR it was deemed unnecessary.) At that time, maintenance therapy after transplant was being discussed but was not normal protocol, so I decided to go drug-free after recovery from the transplant.
Monitoring protein levels every three months, I enjoyed CR drug-free survival until April 2011, about 5 ½ years. In April, increased protein levels prompted a full workup, and a PET scan showed multiple new tumors, as well as a “mass” in my right lung, which my doctors felt was Myeloma, but weren’t sure.
We began treatment immediately with the newly accepted induction regimen, Velcade, Dex, and Revlimid and four Aredia infusions. As in the first induction therapy, I responded well, and within 8 weeks my bloodwork was back to normal; a scan showed that the mass in my lung had disappeared, which indicated it was myeloma. A bone marrow biopsy showed normal results.
Using Stem cells left over from my original harvesting in 2005, in August 2011, I had a second SCT, from which I’m now recovering. So far all looks good, except for a detour taking high-dose prednisone to combat a drug reaction.
My question is, assuming I achieve CR, should I go on maintenance therapy or not?
I seem to have a volatile form of Myeloma; in other words, it grows fast, but it also responds strongly to treatment.
I’m inclined to not do maintenance and treat the multiple myeloma only when it comes back. It seems to me that low-dose therapy might reduce the potency of the drugs to the point that my “high volatility’ disease won’t respond as well as it has in the past to future treatments.
What do you think?
Forums
9 posts
• Page 1 of 1
Re: Maintenance therapy for very responsive multiple myeloma
Jon,
The answer to the question maintenance therapy after high-dose melphalan is not straightforward.
The idea of maintenance is not truly new, but the success and tolerability of Revlimid (lenalidomide) has made an very intriguing and tempting addition to therapy. Two recent phase III randomized placebo controlled studies, CALGB 100104 and IFM 2005-02, have data that suggest maintenance low-doses of Revlimid daily may be beneficial after transplant. However, there are caveats.
First, although both studies have shown that patients benefit in terms of time without measurable disease (Time to progression or Progression Free Survival), this is not the same as surviving longer.
Second, only one of the studies has demonstrated a survival advantage to patients receiving Revlimid over placebo to date, and the actual clinical significance of the percent improvement in survival is not yet defined. So, we still don't truly know if a patient receiving maintance therapy will survival longer than some who was not on maintenance Revlimid, but was treated at relapse.
Third, there are risks involved: you are on a drug with potential side effects (myelosuppression, infection etc), you need to be monitored a bit more closely with labs (Quality of Life), and, importantly, there are potential long term risks associated with Revlimid therapy. In both studies mentioned above as well as a third trial (MM015) looking at Revlimid maintenance after induction therapy with melphalan-containing therapy, there have been reports of second primary malignancies (different cancers). The numbers are very small and we in the myeloma world are still trying to determine how significant a risk this phenomenon may be/is, though it appears that it is not significantly greater than aged-matched individuals outside of the studies. So, they may not be significantly greater than the risk associated with high dose melphalan you received prior to transplant. On balance the risks are very low and we know that the risks of myeloma relapse are nearly 100%. However, it is something needs to weighed when making these decisions.
Fourth, there is a monetary component -- not much is cheaper than no drug.
My personal opinion is that eventually both studies will demonstrate survival advantages, but that has not been demonstrated. I am in favor of maintenance therapy, but I attempt to personalize this mode of therapy. I strongly recommend maintenance Revlimid for individuals who have high risk disease and/or have residual disease after transplant. People with standard risk disease and CR after transplant may benefit equally without drug until relapse when speaking about overall survival. Remember our goal is to control disease, we cannot make it go away (the potential of allogeneic transplant withstanding).
However, there are likely many opinions on this matter and today I don't think that anyone has a rock solid answer, especially in your case.
In your case, you went 5.5 years without maintenance therapy (only needing to see your oncologist every 3 months) and you have achieved a second CR. I am not sure how much maintenance therapy would benefit you in terms of survival. The odds are that it would keep measurable disease away longer (delay relapse). There is little data about the benefits of maintenance in your setting (after second transplant). You will not likely get as much time out of the second transplant, but you will have time and additional options upon relapse. So, this is something that you, your family, and oncologist will have to discuss.
I hope this helps.
The answer to the question maintenance therapy after high-dose melphalan is not straightforward.
The idea of maintenance is not truly new, but the success and tolerability of Revlimid (lenalidomide) has made an very intriguing and tempting addition to therapy. Two recent phase III randomized placebo controlled studies, CALGB 100104 and IFM 2005-02, have data that suggest maintenance low-doses of Revlimid daily may be beneficial after transplant. However, there are caveats.
First, although both studies have shown that patients benefit in terms of time without measurable disease (Time to progression or Progression Free Survival), this is not the same as surviving longer.
Second, only one of the studies has demonstrated a survival advantage to patients receiving Revlimid over placebo to date, and the actual clinical significance of the percent improvement in survival is not yet defined. So, we still don't truly know if a patient receiving maintance therapy will survival longer than some who was not on maintenance Revlimid, but was treated at relapse.
Third, there are risks involved: you are on a drug with potential side effects (myelosuppression, infection etc), you need to be monitored a bit more closely with labs (Quality of Life), and, importantly, there are potential long term risks associated with Revlimid therapy. In both studies mentioned above as well as a third trial (MM015) looking at Revlimid maintenance after induction therapy with melphalan-containing therapy, there have been reports of second primary malignancies (different cancers). The numbers are very small and we in the myeloma world are still trying to determine how significant a risk this phenomenon may be/is, though it appears that it is not significantly greater than aged-matched individuals outside of the studies. So, they may not be significantly greater than the risk associated with high dose melphalan you received prior to transplant. On balance the risks are very low and we know that the risks of myeloma relapse are nearly 100%. However, it is something needs to weighed when making these decisions.
Fourth, there is a monetary component -- not much is cheaper than no drug.
My personal opinion is that eventually both studies will demonstrate survival advantages, but that has not been demonstrated. I am in favor of maintenance therapy, but I attempt to personalize this mode of therapy. I strongly recommend maintenance Revlimid for individuals who have high risk disease and/or have residual disease after transplant. People with standard risk disease and CR after transplant may benefit equally without drug until relapse when speaking about overall survival. Remember our goal is to control disease, we cannot make it go away (the potential of allogeneic transplant withstanding).
However, there are likely many opinions on this matter and today I don't think that anyone has a rock solid answer, especially in your case.
In your case, you went 5.5 years without maintenance therapy (only needing to see your oncologist every 3 months) and you have achieved a second CR. I am not sure how much maintenance therapy would benefit you in terms of survival. The odds are that it would keep measurable disease away longer (delay relapse). There is little data about the benefits of maintenance in your setting (after second transplant). You will not likely get as much time out of the second transplant, but you will have time and additional options upon relapse. So, this is something that you, your family, and oncologist will have to discuss.
I hope this helps.
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Dr. Ken Shain - Name: Ken Shain, M.D., Ph.D.
Beacon Medical Advisor
Re: Maintenance therapy for very responsive multiple myeloma
Dear Dr. Shain,
Thank you for your thoughtful and informative reply.
What kind of time extensions have been achieved for the time to relapse for maintenance vs. non-maintenance?
Any time extension to PFS gained by maintenance should be balanced against the decreased quality of life and added disease risk of taking the maintenance drugs. Add to that the fact that I may only be increasing the interval to PFS, and not overall survival.................. I'm still undecided!
Anyone else have an opinion?
-Jon
Thank you for your thoughtful and informative reply.
What kind of time extensions have been achieved for the time to relapse for maintenance vs. non-maintenance?
Any time extension to PFS gained by maintenance should be balanced against the decreased quality of life and added disease risk of taking the maintenance drugs. Add to that the fact that I may only be increasing the interval to PFS, and not overall survival.................. I'm still undecided!
Anyone else have an opinion?
-Jon
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Jon - Name: Jon
- When were you/they diagnosed?: mar 2005
- Age at diagnosis: 60
Re: Maintenance therapy for very responsive multiple myeloma
Dr Shain,
I really appreciated reading your well thought out response as it covered the waterfront and all the caveats.
Thanks for providing the quality of detail you did.
I really appreciated reading your well thought out response as it covered the waterfront and all the caveats.
Thanks for providing the quality of detail you did.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Maintenance therapy for very responsive multiple myeloma
I apologize for leaving out the most exciting data from the two studies. In patients who received induction of choice and transplant at first remission.
With the end point of time to progression (TTP) in the CALGB 100104 study patients receiving Revlimid maintenance the mean ("average") TTP was 42.3 compared to 21.8 months in patients receiving placebo.
With the end point of progression free survival (PFS) in IFM 2005-02 study patients receiving Revlimid maintenance the mean ("average") PFS was 42 compared to 24 months in patients receiving placebo.
It this time without measurable disease that has created a lot of excitement and widespread aboption of Rev maintenance. However, TTP and PFS are surogate markers for overall survival (OS)- they do not necessarily equate to overall survival. They are excellent surrogates for trials to get active drugs in myeloma in to use- because they don't take as long to calculate as overall survival. However, when it comes to impacting disase OS is likely the best, but takes a long time (which is good news as it means our patients are living a good long time).
It can come down to what you want or what you are mentally prepared to do. Are you someone who wants to be actively addressing the control of your disease? Or are you someing who would you rather think about it as little as possible? It is not an easy decision. The truth is that in this case there is no wrong decision. You "simply" need to educated about the risks and the benefits.
If you tolerate RVD without difficulty you will likely tolerate a lower dose of Revlimid just fine.
There is an article that was published recently in Blood which is very relevant to the topic we have been discussing. It is by Dr. Vincent Rajkumar and two other myeloma specialists, and it's titled "Approach to the treatment of multiple myeloma: a clash of philosophies."
Although the article certainly is technical in spots, it's worth skimming over at some point. Here is a link to the article:
With the end point of time to progression (TTP) in the CALGB 100104 study patients receiving Revlimid maintenance the mean ("average") TTP was 42.3 compared to 21.8 months in patients receiving placebo.
With the end point of progression free survival (PFS) in IFM 2005-02 study patients receiving Revlimid maintenance the mean ("average") PFS was 42 compared to 24 months in patients receiving placebo.
It this time without measurable disease that has created a lot of excitement and widespread aboption of Rev maintenance. However, TTP and PFS are surogate markers for overall survival (OS)- they do not necessarily equate to overall survival. They are excellent surrogates for trials to get active drugs in myeloma in to use- because they don't take as long to calculate as overall survival. However, when it comes to impacting disase OS is likely the best, but takes a long time (which is good news as it means our patients are living a good long time).
It can come down to what you want or what you are mentally prepared to do. Are you someone who wants to be actively addressing the control of your disease? Or are you someing who would you rather think about it as little as possible? It is not an easy decision. The truth is that in this case there is no wrong decision. You "simply" need to educated about the risks and the benefits.
If you tolerate RVD without difficulty you will likely tolerate a lower dose of Revlimid just fine.
There is an article that was published recently in Blood which is very relevant to the topic we have been discussing. It is by Dr. Vincent Rajkumar and two other myeloma specialists, and it's titled "Approach to the treatment of multiple myeloma: a clash of philosophies."
Although the article certainly is technical in spots, it's worth skimming over at some point. Here is a link to the article:
- Attachments
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Blood - Myeloma Treatment - Clash of Philosophies 2011.pdf- (573.89 KiB) Downloaded 133 times
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Dr. Ken Shain - Name: Ken Shain, M.D., Ph.D.
Beacon Medical Advisor
Re: Maintenance therapy for very responsive multiple myeloma
...and speaking for all of the advisors- it is our pleasure to do what we can to assist you.
-
Dr. Ken Shain - Name: Ken Shain, M.D., Ph.D.
Beacon Medical Advisor
Re: Maintenance therapy for very responsive multiple myeloma
Thank You Doctor,
Those results make me lean towards maintenance.
Best,
Jon
Those results make me lean towards maintenance.
Best,
Jon
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Jon - Name: Jon
- When were you/they diagnosed?: mar 2005
- Age at diagnosis: 60
Re: Maintenance therapy for very responsive multiple myeloma
Thank you very much Dr. Shain.
Coincidentally, today I am at day 50 and I will be facing this decision in 50 days.
Now I am much better prepared to discuss maintenance therapy with my doctor.
Thanks again.
Chip
Coincidentally, today I am at day 50 and I will be facing this decision in 50 days.
Now I am much better prepared to discuss maintenance therapy with my doctor.
Thanks again.
Chip
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Chip - Name: Chip
- When were you/they diagnosed?: 20 November 2010
- Age at diagnosis: 58
Re: Is maintenance therapy right for a highly responsive mul
This is another great discussion. I also want to thank Dr. Shain for his extensive comments.
Because this is such an important subject, allow me to play devil's advocate.
Now, I haven't read Dr. Rajkumar's paper yet, so perhaps this point already is made in the article that you've posted.
However, aren't there cases very similar to what we have seen with Revlimid maintenance where progression free survival was seen in a patient population, but longer term follow-up showed no survival benefit?
Consider this article here at the Beacon,
https://myelomabeacon.org/news/2010/07/07/maintenance-thalidomide-improves-progression-free-survival-but-not-overall-survival-eha-2010/
It says that thalidomide, which is chemically very similar to Revlimid, showed a progression free survival benefit in the tested population, but long-term follow-up didn't reveal any survival benefit.
I know that a survival benefit has been found -- so far -- in the CALGB study looking at Revlimid maintenance. But I believe there is no survival benefit yet in the IFM trial or the MM-015 trial, and, if I recall correctly, there isn't even a trend to a significant survival benefit in the patients in those trials.
On the IFM trial and whether or not there is a survival benefit in the data, I found this here at the Beacon:
https://myelomabeacon.org/forum/imw-2011-multiple-myeloma-discussion-day-3-t393.html#p1509
I don't know where I read information about survival in the MM-015 trial. Perhaps I'm not recalling correctly in regard to that trial.
Because this is such an important subject, allow me to play devil's advocate.
Now, I haven't read Dr. Rajkumar's paper yet, so perhaps this point already is made in the article that you've posted.
However, aren't there cases very similar to what we have seen with Revlimid maintenance where progression free survival was seen in a patient population, but longer term follow-up showed no survival benefit?
Consider this article here at the Beacon,
https://myelomabeacon.org/news/2010/07/07/maintenance-thalidomide-improves-progression-free-survival-but-not-overall-survival-eha-2010/
It says that thalidomide, which is chemically very similar to Revlimid, showed a progression free survival benefit in the tested population, but long-term follow-up didn't reveal any survival benefit.
I know that a survival benefit has been found -- so far -- in the CALGB study looking at Revlimid maintenance. But I believe there is no survival benefit yet in the IFM trial or the MM-015 trial, and, if I recall correctly, there isn't even a trend to a significant survival benefit in the patients in those trials.
On the IFM trial and whether or not there is a survival benefit in the data, I found this here at the Beacon:
https://myelomabeacon.org/forum/imw-2011-multiple-myeloma-discussion-day-3-t393.html#p1509
I don't know where I read information about survival in the MM-015 trial. Perhaps I'm not recalling correctly in regard to that trial.
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TerryH
9 posts
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