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Revlimid concerns
Thanks up front for answering. I've read that Revlimid increases the chance for blood cancers or solid tumors. I thought I read about a study that estimated the chance of getting one of these cancers increased to about 8-10% per year with Revlimid. I've been taking 10 mg Revlimid since last December--following an autogolous transplant. My m-protein has declined from .30 following the transplant to .13 over the summer to no trace today--so the Revlimid must be working. What does science say about folks in my situation--continue takng Revlimid--or stop and wait and see. If it's the latter will Revlimid be effective the second time around?
Re: Revlimid concerns
Hi I took Thalidomide & Dex. for about 10 months in 2004 ( I understand Revimid & Thalid. are simular in many respects?) things went along well for quite some time then about 2 years ago I was diagnosed with Prostrate Cancer (PSA of 9.6) then biopsy -and was treated by Cyro (freezing) of prostrate - PSA now .00009 so I guess thats a positive result , I discussed with my Oncologist whether or not the previous treatment for the multiple myeloma might have any bearing on my coming down with Prostrate Cancer his answer was "Not Likely" ? don't know if that's any help for you but thought it might be food for thought. best regards N.G.
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Nipon Ginko - Name: Nipon Ginko
- Who do you know with myeloma?: ME
- When were you/they diagnosed?: 2004
- Age at diagnosis: 66
Re: Revlimid concerns
I have been on Revlimid for about 7 months and was recently diagnosed with two solid breast tumors. Very small. I am concerned it might be due to the Revlimid. I've read where studies show that individuals have 4 times the likelihood of developing secondary cancers when taking Revlimid.
Please let me know if you have experienced something like this or know more.
Thank you
Please let me know if you have experienced something like this or know more.
Thank you
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well365 - Name: Ann
- Who do you know with myeloma?: Patient
- When were you/they diagnosed?: 2012
- Age at diagnosis: 54
Re: Revlimid concerns
Hi Well,
Just curious, is Revlimid the only therapy you have had to treat your myeloma, or did you recieve other chemotherapy prior to or concurrent with the Revlimid?
Just curious, is Revlimid the only therapy you have had to treat your myeloma, or did you recieve other chemotherapy prior to or concurrent with the Revlimid?
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Revlimid concerns
This is a very complex and important issue that continues to evolve in the myeloma field.
The potential for second primary malignancies (the development of cancer other that myeloma) is not something brand new to the field. High dose melphalan (or other drugs associated with ablative therapy) has long been understood to correlate with increased risk of typically bone marrow diseases like MDS or AML, but also other cancers (Krishan et al BBMT 2012). This true in other hematologic diseases as well.
However, this is a growing concerns -- or at least has been highlighted -- becuase of the use of Revlimid in the maintenance setting - post HDM & ASCT and post MPR (melphalan, prednisone and rev). In the three studies published in the New England Joural of Medicine this May (2012) - McCarthy et al; Attal et al; and Palumbo et al. -- significant benefits in terms of length of disease control and overall survival (OS at least in the McCarthy study) was demonstrated in the Rev "maintenance" arms.
However, in the cases of the maintenance post transplant studies both demonstrated a statisitically significant increase in the rate of second primary malignacies (solid and liquid) - essentially 3-4%- 8% in both McCarthy et al and the Attal et al studies. In the Palumbo study MPR and was 7% and and MP without Rev "maintenance" was 3%.
This is a very complicated issue with a number of aspects to consider. The myeloma community continues to acknowledge this and it also needs to be put in perspective (for myeloma therapy as a whole -- every patients needs to weigh the risks and benefits individually with their MD). In all three cases the event free survival still favors the utilization of maintenance Revlimid. This is in part because the risk of myeloma relapse remains uniform. However, without strong overall survival benefits from all three studies we need to continue to be judicious and speak openly with patients about the risk and benefits of maintenance therapy.
Because of these results some oncologist have chosen to stop maintenance after 2 years -- as did the French in the IFM study (Attal et al). Personally, it is a question that remains incompletely answered. I generally recommend maintenance therapy after HDM-ASCT to my patients. The favorable data remains very strong. The desicion must also be patient endorsed as well. I treat for two years and reassess at that time and if all criteria have been met (control of disease, excellent tolerance (quality of life), limited adverse events) we continue.
I ask that patients continue to get age appropriate cancer screening.
Continued Revlimid in the absence of melphalan therapy (in both the newly diagnosed and relapsed setting- relapsed and refractory was specifically examined in Dimopolous et al Blood 2012) does not appear to have the same issues. However, this remains an evolving field of study.
The potential for second primary malignancies (the development of cancer other that myeloma) is not something brand new to the field. High dose melphalan (or other drugs associated with ablative therapy) has long been understood to correlate with increased risk of typically bone marrow diseases like MDS or AML, but also other cancers (Krishan et al BBMT 2012). This true in other hematologic diseases as well.
However, this is a growing concerns -- or at least has been highlighted -- becuase of the use of Revlimid in the maintenance setting - post HDM & ASCT and post MPR (melphalan, prednisone and rev). In the three studies published in the New England Joural of Medicine this May (2012) - McCarthy et al; Attal et al; and Palumbo et al. -- significant benefits in terms of length of disease control and overall survival (OS at least in the McCarthy study) was demonstrated in the Rev "maintenance" arms.
However, in the cases of the maintenance post transplant studies both demonstrated a statisitically significant increase in the rate of second primary malignacies (solid and liquid) - essentially 3-4%- 8% in both McCarthy et al and the Attal et al studies. In the Palumbo study MPR and was 7% and and MP without Rev "maintenance" was 3%.
This is a very complicated issue with a number of aspects to consider. The myeloma community continues to acknowledge this and it also needs to be put in perspective (for myeloma therapy as a whole -- every patients needs to weigh the risks and benefits individually with their MD). In all three cases the event free survival still favors the utilization of maintenance Revlimid. This is in part because the risk of myeloma relapse remains uniform. However, without strong overall survival benefits from all three studies we need to continue to be judicious and speak openly with patients about the risk and benefits of maintenance therapy.
Because of these results some oncologist have chosen to stop maintenance after 2 years -- as did the French in the IFM study (Attal et al). Personally, it is a question that remains incompletely answered. I generally recommend maintenance therapy after HDM-ASCT to my patients. The favorable data remains very strong. The desicion must also be patient endorsed as well. I treat for two years and reassess at that time and if all criteria have been met (control of disease, excellent tolerance (quality of life), limited adverse events) we continue.
I ask that patients continue to get age appropriate cancer screening.
Continued Revlimid in the absence of melphalan therapy (in both the newly diagnosed and relapsed setting- relapsed and refractory was specifically examined in Dimopolous et al Blood 2012) does not appear to have the same issues. However, this remains an evolving field of study.
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Dr. Ken Shain - Name: Ken Shain, M.D., Ph.D.
Beacon Medical Advisor
Re: Revlimid concerns
I was treated with Velcade/dex/rev - 5 rounds. I chose not to undergo stem cell transplant due to the risk of secondary cancers. I'm visitng with my hematologist/oncologist today. I have to believe its is much more than a coincidence. I have no history of cancers in my family, have lead a very healthy lifestyle, no smoking, organic products, healthy weight, healthy exercise. Seven months after being on Revlimid I develop 2 breast tumors. No other health problems! Haven't even had a cold or flu in 15++ years!
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well365 - Name: Ann
- Who do you know with myeloma?: Patient
- When were you/they diagnosed?: 2012
- Age at diagnosis: 54
Re: Revlimid concerns
Well365,
Wow...Very interesting.
Sounds like you have a very robust immune system, with no colds/flu in 15 years!.
So sorry to hear this news after you made the best choices given the therapeutic regimens available. I will be scheduling a mammogram pronto.
As you were aware, we know there is a high incidence of SPM (liquid/solid) following HDT,(without lenalidomide maintenance) and you indicate you did not agree to HDT for these reasons. Neither did I for much the same reason, I am also skeptical of the therapeutic efficacy of HDT for multiple myeloma, as well as the survival data being dismal for high-risk cytogenetic profiles. Just my personal viewpoint.
As Dr. Shain indicated, in the studies cited, the highest incidence of secondary cancers were in patients who received HDT with akylators as part of their induction regimen.
However, what you are indicating, are concerns with SPM without use of alkylator containing regimen prior to maintenance with lenalidomide. That is concerning.
Slides on SPM begin at slide 10
http://myeloma.org/pdfs/Best-of-ASH-2011_01-25-12.pdf
Please let us know what your heme/onc says.
Two other thoughts, one on anti-angiogenesis therapy and the data on VEGF (vascular endothelial growth factor) which was studied in other cancers i.e. pancreatic, breast, and prostate and animal models.
lenalidomide is a known VEGF inhibitor (anti-angiogenesis):
"Early studies showed that Thalidomide had anti angiogenic activity in a rabbit model of corneal neovascularization that was induced as a response to bFGF. This report led to its use in Multiple Myeloma, where it demonstrated clinical benefit and was approved for use by the FDA. Thalidomide and the newer IMiDs have also been shown to significantly decrease the expression of angiogenic factors VEGF and Interleukin-6 (IL-6) in multiple myeloma; thereby reducing angiogenesis and hence contributing to clinical activity in multiple myeloma[26]. The newer IMiDs were found to be 2–3 times more potent compared to thalidomide in antiangiogenic activity in various vivo assays The antiangiogenic activity of both thalidomide and IMiDs has also been shown to be independent of immunomodulatory effects."
http://www.jhoonline.org/content/2/1/36
While inhibiting VEGF was initially thought to be sound therapy, a couple of recent controversies in the field of angiogenesis have fascinated scientists and clinicians alike, namely:
Does VEGF inhibition lead to more aggressive tumours?
What drives metastases and invasion?
What is the role of tumour hypoxia in this process?
Data was originally presented in glioblastoma by Rubenstein et al., (2000), showing that anti-VEGF antibody treatment prolonged survival, but resulted in increased vascularity caused quite a stir. Several other groups subsequently demonstrated in preclinical models that VEGF signaling shrinks tumours, but also results in increased invasion and metastases (see Casanovas et al., (2005), Ebos et al., (2009), Paez-Ribes et al., (2009), for examples).....
...Other experiments were performed with both PF-04217903 and crizotinib (MET inhibitors), as well as cabozantinib, a dual inhibitor of MET and VEGF. When both targets were inhibited together, using either cabozantinib or PF-04217903 plus sunitinib, there was a consistent reduction in invasion and metastases. This also increased with tumour hypoxia and c-MET expression.
http://www.ncbi.nlm.nih.gov/pubmed/19249680
http://www.ncbi.nlm.nih.gov/pubmed/19249681
IOW's, it seems that inhibiting VEGF alone can increase metasasis, even though that is counter-intuitive...the good news is that MET inhibitors given with VEGF inhibitors reduces the risk of SPM/metastases.
Lastly,
Did you have a cytogenetic profile (FISH) done? Do you have any of the high risk chromosomal deletions/gains/translocations? Deletion of TP53 also called 17p is found in most/majority of cancers.
http://www.nature.com/scitable/topicpage/p53-the-most-frequently-altered-gene-in-14192717
Perhaps, this information may be useful, in terms of potential areas to investigate.
Sending you blessings for highly effective therapeutic options and hope for positive outcomes.
Wow...Very interesting.
Sounds like you have a very robust immune system, with no colds/flu in 15 years!.
So sorry to hear this news after you made the best choices given the therapeutic regimens available. I will be scheduling a mammogram pronto.
As you were aware, we know there is a high incidence of SPM (liquid/solid) following HDT,(without lenalidomide maintenance) and you indicate you did not agree to HDT for these reasons. Neither did I for much the same reason, I am also skeptical of the therapeutic efficacy of HDT for multiple myeloma, as well as the survival data being dismal for high-risk cytogenetic profiles. Just my personal viewpoint.
As Dr. Shain indicated, in the studies cited, the highest incidence of secondary cancers were in patients who received HDT with akylators as part of their induction regimen.
However, what you are indicating, are concerns with SPM without use of alkylator containing regimen prior to maintenance with lenalidomide. That is concerning.
Slides on SPM begin at slide 10
http://myeloma.org/pdfs/Best-of-ASH-2011_01-25-12.pdf
Please let us know what your heme/onc says.
Two other thoughts, one on anti-angiogenesis therapy and the data on VEGF (vascular endothelial growth factor) which was studied in other cancers i.e. pancreatic, breast, and prostate and animal models.
lenalidomide is a known VEGF inhibitor (anti-angiogenesis):
"Early studies showed that Thalidomide had anti angiogenic activity in a rabbit model of corneal neovascularization that was induced as a response to bFGF. This report led to its use in Multiple Myeloma, where it demonstrated clinical benefit and was approved for use by the FDA. Thalidomide and the newer IMiDs have also been shown to significantly decrease the expression of angiogenic factors VEGF and Interleukin-6 (IL-6) in multiple myeloma; thereby reducing angiogenesis and hence contributing to clinical activity in multiple myeloma[26]. The newer IMiDs were found to be 2–3 times more potent compared to thalidomide in antiangiogenic activity in various vivo assays The antiangiogenic activity of both thalidomide and IMiDs has also been shown to be independent of immunomodulatory effects."
http://www.jhoonline.org/content/2/1/36
While inhibiting VEGF was initially thought to be sound therapy, a couple of recent controversies in the field of angiogenesis have fascinated scientists and clinicians alike, namely:
Does VEGF inhibition lead to more aggressive tumours?
What drives metastases and invasion?
What is the role of tumour hypoxia in this process?
Data was originally presented in glioblastoma by Rubenstein et al., (2000), showing that anti-VEGF antibody treatment prolonged survival, but resulted in increased vascularity caused quite a stir. Several other groups subsequently demonstrated in preclinical models that VEGF signaling shrinks tumours, but also results in increased invasion and metastases (see Casanovas et al., (2005), Ebos et al., (2009), Paez-Ribes et al., (2009), for examples).....
...Other experiments were performed with both PF-04217903 and crizotinib (MET inhibitors), as well as cabozantinib, a dual inhibitor of MET and VEGF. When both targets were inhibited together, using either cabozantinib or PF-04217903 plus sunitinib, there was a consistent reduction in invasion and metastases. This also increased with tumour hypoxia and c-MET expression.
http://www.ncbi.nlm.nih.gov/pubmed/19249680
http://www.ncbi.nlm.nih.gov/pubmed/19249681
IOW's, it seems that inhibiting VEGF alone can increase metasasis, even though that is counter-intuitive...the good news is that MET inhibitors given with VEGF inhibitors reduces the risk of SPM/metastases.
Lastly,
Did you have a cytogenetic profile (FISH) done? Do you have any of the high risk chromosomal deletions/gains/translocations? Deletion of TP53 also called 17p is found in most/majority of cancers.
http://www.nature.com/scitable/topicpage/p53-the-most-frequently-altered-gene-in-14192717
Perhaps, this information may be useful, in terms of potential areas to investigate.
Sending you blessings for highly effective therapeutic options and hope for positive outcomes.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Revlimid concerns
Yes, I had the fish profile and did not have any of the high risk chromosome abnormalities. I have an incredible immune system, for which I am very very grateful.
My hematologist/oncologist agreed with my assessment of what I had read. We can not definitively say that the Revlimid is the "cause" of the breast tumors, and at the same time we cannot definitively say that Revlimid is NOT the "cause" of the breast tumors. I'm off the Revlimid and will follow up with my hem/onc in January. We'll watch the M-spike, etc. more closely for now.
I was very lucky in that they caught the breast tumors when they were very small. Actually two different types of cancers, which I think makes the Revlimid even more suspect. I've had the tumors removed and will be starting radiation treatment next week. The lymph nodes are healthy. No chemo. However, I will be watched much more closely.
I appreciate your input!!!
My hematologist/oncologist agreed with my assessment of what I had read. We can not definitively say that the Revlimid is the "cause" of the breast tumors, and at the same time we cannot definitively say that Revlimid is NOT the "cause" of the breast tumors. I'm off the Revlimid and will follow up with my hem/onc in January. We'll watch the M-spike, etc. more closely for now.
I was very lucky in that they caught the breast tumors when they were very small. Actually two different types of cancers, which I think makes the Revlimid even more suspect. I've had the tumors removed and will be starting radiation treatment next week. The lymph nodes are healthy. No chemo. However, I will be watched much more closely.
I appreciate your input!!!
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well365 - Name: Ann
- Who do you know with myeloma?: Patient
- When were you/they diagnosed?: 2012
- Age at diagnosis: 54
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