My mother was diagnosed October 14, 2016. She is an ISS Stage 1 but has the 17p deletion. She was started on Revlimid, Velcade, and dexamethasone (RVD) and initially responded beautifully! She went down almost 90% in 2 cycles. The third cycle she went up a small bit (not statistically significant) and the 4th cycle even more. It was still probably an 85% response.
She went to have lab work done and her transplant consent signed a couple of weeks after her 4th cycle was finished. While she went up to get her retrieval, she received news that they would have to delay the transplant. Her numbers were back up and were only about 65% lower than her original. Needless to say, we were so upset, not so much that she would have the transplant pushed back, but that the numbers went back up so much and so quickly.
I am discouraged for two reasons: RVD not working at induction when it does seem to work for so many people, and already jumping to another drug regimen so soon into treatment. The doctor is doing Pomalyst, Darzalex, and dexamethasone for 8 weeks, and then right into transplant if she responds.
I have not heard of this combination being given before transplant. Is it common, or not so common? I would welcome, of course, any encouragement in regard to her RVD not being effective as of now.
Thank you so very much.
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mimigrin - Name: Mimi
- Who do you know with myeloma?: Mother
- When were you/they diagnosed?: October 2016
- Age at diagnosis: 62
Re: Pomalyst, Darzalex & dex before transplant - how common?
Hi Mimigrin,
Sounds like your mother is lucky to have you for a daughter. A great caregiver / team of caregivers was vital for me to have a great outcome as a high-risk patient diagnosed back in 2010.
Being termed "high risk" means that an individual patient is not likely to have as good of an outcome (typically defined by median overall survival or time in first remission) given the standard therapies of the day. Darzalex is a newly approved therapy. There is little (any?) data when using it as part of a patient's upfront therapy, on standard or high-risk patients. The "positive spin" is that it is possible that 10 years from now it will be standard to use Darzalex on a newly diagnosed patient that has 17P deletion because it works so well and your mother was one of the early patients that benefited.
I had multiple high risk features back in 2010 when I was diagnosed. My main piece of advice would be to ask about doing things a little different than a standard risk patient. As an example, you mention doing a planned autologous stem cell transplant. The standard conditioning for an auto transplant is high-dose melphalan alone. Ask if they could or are planning to add a proteasome inhibitor (Velcade or Kyprolis) to the conditioning. Proteasome inhibitors and alkylators seem to have good synergy. Here is a recent study using a proteasome inhibitor, immunomodulatory agent, and dexamethasone combination as part of the conditioning showing good activity for patients that do autos.
Kalyan Nadiminti, K, et al, "VTD-melphalan is well tolerated and results in very high rates of stringent CR and MRD-negative status in multiple myeloma," OncoTargets and Therapy, 2017 (full text of article)
Another example is that a drug called Farydak (panobinostat) was recently approved. It seems to have synergy with proteasome inhibitors, but it does not seem like it is commonly used. The high risk patients that I have seen that do well seem to get benefit from proteasome inhibitors. Combining it with an immunomodulatory agent did not give your mother much benefit, so it may be helpful to try and find another therapy to combine it with to gain benefit. I do not have any experience using Darzalex, Farydak, etc., so I cannot give you any first-hand experience on what quality of life is like during / after using those therapies.
Good luck moving forward. Hopefully the Darzalex, Pomalyst, and dexamethasone combination will achieve a deep response for the auto and get your mother on the road to a long remission.
Mark
Sounds like your mother is lucky to have you for a daughter. A great caregiver / team of caregivers was vital for me to have a great outcome as a high-risk patient diagnosed back in 2010.
Being termed "high risk" means that an individual patient is not likely to have as good of an outcome (typically defined by median overall survival or time in first remission) given the standard therapies of the day. Darzalex is a newly approved therapy. There is little (any?) data when using it as part of a patient's upfront therapy, on standard or high-risk patients. The "positive spin" is that it is possible that 10 years from now it will be standard to use Darzalex on a newly diagnosed patient that has 17P deletion because it works so well and your mother was one of the early patients that benefited.
I had multiple high risk features back in 2010 when I was diagnosed. My main piece of advice would be to ask about doing things a little different than a standard risk patient. As an example, you mention doing a planned autologous stem cell transplant. The standard conditioning for an auto transplant is high-dose melphalan alone. Ask if they could or are planning to add a proteasome inhibitor (Velcade or Kyprolis) to the conditioning. Proteasome inhibitors and alkylators seem to have good synergy. Here is a recent study using a proteasome inhibitor, immunomodulatory agent, and dexamethasone combination as part of the conditioning showing good activity for patients that do autos.
Kalyan Nadiminti, K, et al, "VTD-melphalan is well tolerated and results in very high rates of stringent CR and MRD-negative status in multiple myeloma," OncoTargets and Therapy, 2017 (full text of article)
Another example is that a drug called Farydak (panobinostat) was recently approved. It seems to have synergy with proteasome inhibitors, but it does not seem like it is commonly used. The high risk patients that I have seen that do well seem to get benefit from proteasome inhibitors. Combining it with an immunomodulatory agent did not give your mother much benefit, so it may be helpful to try and find another therapy to combine it with to gain benefit. I do not have any experience using Darzalex, Farydak, etc., so I cannot give you any first-hand experience on what quality of life is like during / after using those therapies.
Good luck moving forward. Hopefully the Darzalex, Pomalyst, and dexamethasone combination will achieve a deep response for the auto and get your mother on the road to a long remission.
Mark
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Mark11
Re: Pomalyst, Darzalex & dex before transplant - how common?
Mimi,
I was diagnosed in April 2015, and I'm also del(17p) high-risk. I had a very similar experience to your mother. I started treatment with Revlimid, Velcade, dex (RVD), and I responded to the first two cycles before seeing a slight uptick in my M-spike after the third. My doctor didn't even hesitate to change my medications to Kyprolis, Pomalyst, and dex (KPD), and I saw a quick and deep response that set me up for a successful autologous stem cell transplant.
I haven't used Darzalex, but it sounds like her doctor is taking the same steps with her as mine did with me. When RVD didn't give a good response, move to the newer medications that have shown benefits for high-risk patients.
I totally understand your concern about moving so quickly past the "standard treatment", but I wouldn't put too much time into worrying about that and be glad there are some medications out there that appear to be so effective for us.
I was diagnosed in April 2015, and I'm also del(17p) high-risk. I had a very similar experience to your mother. I started treatment with Revlimid, Velcade, dex (RVD), and I responded to the first two cycles before seeing a slight uptick in my M-spike after the third. My doctor didn't even hesitate to change my medications to Kyprolis, Pomalyst, and dex (KPD), and I saw a quick and deep response that set me up for a successful autologous stem cell transplant.
I haven't used Darzalex, but it sounds like her doctor is taking the same steps with her as mine did with me. When RVD didn't give a good response, move to the newer medications that have shown benefits for high-risk patients.
I totally understand your concern about moving so quickly past the "standard treatment", but I wouldn't put too much time into worrying about that and be glad there are some medications out there that appear to be so effective for us.
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Mark Pouley - Name: Mark
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: April 2015
- Age at diagnosis: 53
Re: Pomalyst, Darzalex & dex before transplant - how common?
Mark11,
Were you given high-dose melphalan alone or was a proteasome inhibitor added? I am a little confused why he is getting Darzalex with induction. I have searched and searched for clinical trials where it is has been used for this but cannot find any anywhere.
Were you given high-dose melphalan alone or was a proteasome inhibitor added? I am a little confused why he is getting Darzalex with induction. I have searched and searched for clinical trials where it is has been used for this but cannot find any anywhere.
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mimigrin - Name: Mimi
- Who do you know with myeloma?: Mother
- When were you/they diagnosed?: October 2016
- Age at diagnosis: 62
Re: Pomalyst, Darzalex & dex before transplant - how common?
Hi Mimi,
Your mother should not be walking out of meeting with her doctor not knowing why he/she made a therapy change. In my opinion it is vital to a great outcome for a doctor and patient to have an excellent rapport so the patient understands why they are using a particular therapy and what the potential benefits and side effects of the therapies they are using are.
If I were to guess why your doctor switched to Darzalex and why I think you should you view it as a positive, I will show you the results of a recent Mayo Clinic retrospective study. The time period of the study is 2007 to 2015 and the patients were high risk that did an auto with high dose melphalan. Given the time period, they relied on proteasome inhibitors (PIs) and immunomodulatory agents (IMids) as well. They were trying to see if high risk patients that responded well (stringent complete response and MRD negative status via flow) had improved outcomes compared to high risk patients that did not respond as well. Unfortunately this is what they found with 17P:
"In the subgroups with deletion(17p) (n=84) and those with ≥2 HR cytogenetic abnormalities (n=32), sCR and MRD-negativity did not translate into a superior PFS or OS. In patients with t(4;14) (n=65), sCR post-transplant led to a trend towards superior PFS and MRD-negativity translated into significantly superior PFS and OS. Depth of response and MRD status are important surrogate markers for survival in patients with HR cytogenetics, except in the subgroups with deletion(17p) and ≥2 HR abnormalities, where sCR and MRD-negativity post-transplant did not translate into a superior survival."
Source:
Chakraborty, R, et al, "Impact of Post-Transplant Response and Minimal Residual Disease on Survival in Myeloma with High-Risk Cytogenetics," Biology of Blood and Marrow Transplantation, Jan 2017 (abstract)
While there are examples of patients that have good outcomes using standard therapies of that time period, it is not likely that 17P patients that respond well to those therapies will have a particularly good outcome. I would look at it like your mother is getting an opportunity to use another class of therapy that may be effective for a 17P patient when combined with the standard therapies early in disease course. She can still use those if the Darzalex is not beneficial.
Fortunately I have not needed any myeloma therapy since 2011, so I do not know if it is common for insurance companies to approve these newly approved therapies early in disease course. It sounds like your mother has a good insurance company if Darzalex was approved for use this early, so I would view that as a positive as well.
I did not combine high-dose melphalan with a proteasome inhibitor when I did my auto. Doing an auto was not in my original treatment plan. The original plan was to do Velcade, Doxil, and dexamethasone until I got to a complete response (CR) and than do an allogeneic transplant. My insurance company only would pay for a tandem auto followed by an allo. The main advantage to doing an allo is that the donor immune system provides long-term maintenance, so all I needed my auto to do was get me from very good partial response (VGPR) to CR and hold it for 4 months until I did the allo. Your mother is going to need more benefit from her auto than I did, that is one reason I think she should ask your doctor about adding some other therapy to the high dose melphalan.
You seem worried that your mother may be treated differently than other patients, most of whom are standard risk patients. In 2011, the year I did my allo, it's my understanding that less than 20 myeloma patients did an allo from an unrelated donor while in remission like I did. I have seen estimates that somewhere between 20,000 to 25,000 patients are diagnosed with myeloma in a given year, so it is extremely rare for a patient to be treated like I was. It is also rare for a high risk patient to be considered cured of myeloma like I am. That is why I stated in my first post that my advice to you would be to try and have your mother treat differently than most other patients. Treating different than other patients worked out very well for this formerly high risk patient. Hopefully your mother will also have a great outcome and you look back on the switch to Darzalex as the start of it.
Mark
Your mother should not be walking out of meeting with her doctor not knowing why he/she made a therapy change. In my opinion it is vital to a great outcome for a doctor and patient to have an excellent rapport so the patient understands why they are using a particular therapy and what the potential benefits and side effects of the therapies they are using are.
If I were to guess why your doctor switched to Darzalex and why I think you should you view it as a positive, I will show you the results of a recent Mayo Clinic retrospective study. The time period of the study is 2007 to 2015 and the patients were high risk that did an auto with high dose melphalan. Given the time period, they relied on proteasome inhibitors (PIs) and immunomodulatory agents (IMids) as well. They were trying to see if high risk patients that responded well (stringent complete response and MRD negative status via flow) had improved outcomes compared to high risk patients that did not respond as well. Unfortunately this is what they found with 17P:
"In the subgroups with deletion(17p) (n=84) and those with ≥2 HR cytogenetic abnormalities (n=32), sCR and MRD-negativity did not translate into a superior PFS or OS. In patients with t(4;14) (n=65), sCR post-transplant led to a trend towards superior PFS and MRD-negativity translated into significantly superior PFS and OS. Depth of response and MRD status are important surrogate markers for survival in patients with HR cytogenetics, except in the subgroups with deletion(17p) and ≥2 HR abnormalities, where sCR and MRD-negativity post-transplant did not translate into a superior survival."
Source:
Chakraborty, R, et al, "Impact of Post-Transplant Response and Minimal Residual Disease on Survival in Myeloma with High-Risk Cytogenetics," Biology of Blood and Marrow Transplantation, Jan 2017 (abstract)
While there are examples of patients that have good outcomes using standard therapies of that time period, it is not likely that 17P patients that respond well to those therapies will have a particularly good outcome. I would look at it like your mother is getting an opportunity to use another class of therapy that may be effective for a 17P patient when combined with the standard therapies early in disease course. She can still use those if the Darzalex is not beneficial.
Fortunately I have not needed any myeloma therapy since 2011, so I do not know if it is common for insurance companies to approve these newly approved therapies early in disease course. It sounds like your mother has a good insurance company if Darzalex was approved for use this early, so I would view that as a positive as well.
I did not combine high-dose melphalan with a proteasome inhibitor when I did my auto. Doing an auto was not in my original treatment plan. The original plan was to do Velcade, Doxil, and dexamethasone until I got to a complete response (CR) and than do an allogeneic transplant. My insurance company only would pay for a tandem auto followed by an allo. The main advantage to doing an allo is that the donor immune system provides long-term maintenance, so all I needed my auto to do was get me from very good partial response (VGPR) to CR and hold it for 4 months until I did the allo. Your mother is going to need more benefit from her auto than I did, that is one reason I think she should ask your doctor about adding some other therapy to the high dose melphalan.
You seem worried that your mother may be treated differently than other patients, most of whom are standard risk patients. In 2011, the year I did my allo, it's my understanding that less than 20 myeloma patients did an allo from an unrelated donor while in remission like I did. I have seen estimates that somewhere between 20,000 to 25,000 patients are diagnosed with myeloma in a given year, so it is extremely rare for a patient to be treated like I was. It is also rare for a high risk patient to be considered cured of myeloma like I am. That is why I stated in my first post that my advice to you would be to try and have your mother treat differently than most other patients. Treating different than other patients worked out very well for this formerly high risk patient. Hopefully your mother will also have a great outcome and you look back on the switch to Darzalex as the start of it.
Mark
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Mark11
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