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Would you consider treatment for High Risk Smoldering multiple myeloma?
I would welcome the community's thoughts on early treatment of High Risk Smoldering multiple myeloma (high risk for progression to active disease) in the clinical trial setting. I am aware of early clinical trial intervention studies with Revlimid w/ Dex (Spanish study group as well as some centers in the US, I believe Dr. Lonial @ Emory ) and Carfilzomib, Revlimid w/ Dex (NIH w/ Dr. Landgren). Have any smolderers considered this and actually participate(d) in these trials? Or would anyone currently under treatment for active multiple myeloma have or had considered this option prior to commencing treatment once their multiple myeloma became active, had you known you were at high risk for progression ? All opinions will be very much appreciated.
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DanaH - Who do you know with myeloma?: Myself, SMM as of 1/2012
- When were you/they diagnosed?: 1/2012
- Age at diagnosis: 54
Re: Would you consider treatment for High Risk Smoldering mu
Dana H,
I am in the NIH trial.
I went to the NIH and had all the testing done planning to enter the natural history study. My testing showed that i was a high risk smolderer according to the both the italian and spanish study protocol.
Dr Landgren felt that I had a 75% chance of converting to active myeloma in the next two years. They had introduced the CRD for smolderers at a previous visit so I was already considering it and those odds were not for me. I didn't want to wait to be symptomatic before starting to fight it.
They are having great results thus far!
You need to meet them and have an evaluation before you think too much about this. Nothing wrong with standard therapy. Lots involved in making a decision like this besides the labs.
Can you get there easily, (its an eight month treatment, almost weekly). You may or may not be able to work depending on your response to the meds and what kind of job you have. Expenses are not totally covered. Your comfort level with the docs.
Good luck with your eval and your decision.
I am in the NIH trial.
I went to the NIH and had all the testing done planning to enter the natural history study. My testing showed that i was a high risk smolderer according to the both the italian and spanish study protocol.
Dr Landgren felt that I had a 75% chance of converting to active myeloma in the next two years. They had introduced the CRD for smolderers at a previous visit so I was already considering it and those odds were not for me. I didn't want to wait to be symptomatic before starting to fight it.
They are having great results thus far!
You need to meet them and have an evaluation before you think too much about this. Nothing wrong with standard therapy. Lots involved in making a decision like this besides the labs.
Can you get there easily, (its an eight month treatment, almost weekly). You may or may not be able to work depending on your response to the meds and what kind of job you have. Expenses are not totally covered. Your comfort level with the docs.
Good luck with your eval and your decision.
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mrsv118 - Name: Kate
- Who do you know with myeloma?: ME
- When were you/they diagnosed?: 7/19/12
- Age at diagnosis: 48
Re: Would you consider treatment for High Risk Smoldering mu
Hi Kate,
Thanks so much for your reply. I am so happy to hear the treatment is working for you, it seems you made a great decision. Hopefully will be going to the NIH late spring/early summer for evaluation & consultation. I look forward to having them share their experience. Best of luck to you.
May I ask how you are monitored during this clinical trial? And are the weekly visits just 1 day? I could work that out if I could travel round trip in a single day, which is doable for me. But I wonder if you need to be near for them to monitor any potential side effects?
Best to you,
Dana
Thanks so much for your reply. I am so happy to hear the treatment is working for you, it seems you made a great decision. Hopefully will be going to the NIH late spring/early summer for evaluation & consultation. I look forward to having them share their experience. Best of luck to you.
May I ask how you are monitored during this clinical trial? And are the weekly visits just 1 day? I could work that out if I could travel round trip in a single day, which is doable for me. But I wonder if you need to be near for them to monitor any potential side effects?
Best to you,
Dana
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DanaH - Who do you know with myeloma?: Myself, SMM as of 1/2012
- When were you/they diagnosed?: 1/2012
- Age at diagnosis: 54
Re: Would you consider treatment for High Risk Smoldering mu
The natural history study doesn't require much time there at all, but the initial eval was two or three days if I remember correctly.
The smoldering treatment study is two days a week with one week at home taking oral dex. that continues for 8 months. The workup for that is also a few days in a row.
I live about two hours away by car so its do-able for me. My employer has been very accomodating as well. I'm a staff nurse at a childrens hospital and for me working full days again hasn't happened yet. Hoping my stamina improves soon.
The smoldering treatment study is two days a week with one week at home taking oral dex. that continues for 8 months. The workup for that is also a few days in a row.
I live about two hours away by car so its do-able for me. My employer has been very accomodating as well. I'm a staff nurse at a childrens hospital and for me working full days again hasn't happened yet. Hoping my stamina improves soon.
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mrsv118 - Name: Kate
- Who do you know with myeloma?: ME
- When were you/they diagnosed?: 7/19/12
- Age at diagnosis: 48
Re: Would you consider treatment for High Risk Smoldering mu
Thanks Kate, How are you feeling on this therapy regime? Have you experienced any side effects? When did you begin the treatment? So much to think about, I know.
Best,
Dana
Best,
Dana
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DanaH - Who do you know with myeloma?: Myself, SMM as of 1/2012
- When were you/they diagnosed?: 1/2012
- Age at diagnosis: 54
Re: Would you consider treatment for High Risk Smoldering mu
Dear Dana H,
I think consideration of a clinical trial for high-risk smoldering myeloma is a great idea, and the NIH study you mentioned is a terrific option.
On what basis are you considered high-risk and how long have you been diagnosed? There are certain features that I would consider very high-risk that should prompt consideration for early treatment, in a clinical trial or otherwise. >60% myeloma cells on bone marrow biopsy is associated with a rapid progression to symptomatic myeloma as is a serum free light chain ratio (involved serum free light chain/uninvolved serum free light chain)>100. Additionally, >1 bone lesion seen on MRI is associated with a more rapid evolution to symptomatic myeloma.
Let us know what you decide to do. Good luck!
Pete V.
I think consideration of a clinical trial for high-risk smoldering myeloma is a great idea, and the NIH study you mentioned is a terrific option.
On what basis are you considered high-risk and how long have you been diagnosed? There are certain features that I would consider very high-risk that should prompt consideration for early treatment, in a clinical trial or otherwise. >60% myeloma cells on bone marrow biopsy is associated with a rapid progression to symptomatic myeloma as is a serum free light chain ratio (involved serum free light chain/uninvolved serum free light chain)>100. Additionally, >1 bone lesion seen on MRI is associated with a more rapid evolution to symptomatic myeloma.
Let us know what you decide to do. Good luck!
Pete V.
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Dr. Peter Voorhees - Name: Peter Voorhees, M.D.
Beacon Medical Advisor
Re: Would you consider treatment for High Risk Smoldering mu
Dear Dr. Voorhees,
I definitely don’t have the critical features you mention above, and I am very grateful you took the time to explain this to me. My story is as follows.
Diagnosed MGUS IGg Kappa in December, 2010 based upon 8% PC aspirate, no chromosome abnormality w/ FISH/Cytogenetics, no amyloid in BMB. Normal abdominal fat pad biopsy.
2nd BM Biopsy in 1/12/2012 reflected 6% PC upon aspirate ; 5%-10 % and 10%-15% in core biopsy (details below) Based upon PC% >10%, with 97% aberrant PC and IgA immunoparesis, reclassified as High Risk SMM per Spanish (PETHEMA) study.
No bone lesions per PET/FDG/CT scan and full spine MRI, but per DEXA interim bone demineralization/beginning of severe osteopenia in femoral neck and lumbar spine, hip is normal.
Zometa IV started October, 2012, every 3 months.
IgG ranging from 1235 – 1365 mg/L; IgA immunoparesis (46 mg/L) IgM normal (95 mg/L)
FLC Kappa steadily increasing from 33.46 – 54.34 mg/L., Lambda 6.34 – 5.9, Ratio 5.278 – 9.21
M-spike has remained steady @ 0.80 G/dL.
Normal Hgb 13.1, Creatitine 0.81. , Albumin 4.5 G/dL.
Lymphopenia (ranging 0.8-1.1)
Foamy Urine/proteinuria, but no Bence Jones M-spike, TP 72 mg/24 hours @100% Albumin @ 3/2011; TP 126 mg/24 hours @ 27% Albumin, 20% Alpha 1, 14% Alpha 2, 30% Beta, 8.7% Gamma 10/2012
55 years old post menopausal (2007), mild night sweats and fatigue.
Hashimoto’s, normal thyroid function. Open angle glaucoma. High cholesterol.
Viral pneumonia 10/1990, strep throat infection w/left tonsil abscess 9/2012, frequent sinus infections.
Constant Neuropathy in hands/lower arms, feet/lower legs started in June, 2009. All neuro (EMG/NCS & Epidermal Nerve Fiber Density Skin Biopsy- no amyloid) and autoimmune serum tests normal.
1/12/2012 BONE MARROW BIOPSY.
DIAGNOSIS: bone marrow biopsy, aspirate and peripheral smear:
- Variably cellular bone marrow with increased atypical Cyclin-D1 positive plasma cells with Kappa light chain predominance
- Maturing trilineage hematopoiesis
- High Risk SMM DIAGNOSIS due to 97% aberrant cells of the 10% “averaged” plasma cells upon flow cytometry coupled with IgA immunoparesis per PETHEMA (Spanish risk progression study)
Comment: The percentage of plasma cells varies within the biopsy: some area have 5-10% plasma cells while other areas have 10-15% plasma cells.
MARROW BIOPSY Sections:
Cellularity is variable ranging from 20-40%, overall 30% cellular.
Megakaryocytes: present, non-dysplastic
M:E ratio 2:1
Immunohistochemical stains:
CD138 immunostain highlights increased plasma cells which vary in concentration within the biopsy; some areas contain 10-15% plasma cells while other areas contain 5-10% plasma cells. The plasma cells are positive for Cyclin D1 and negative for CD 56, CD117 and CD20. Kappa and Lambda immunostains as well as Kappa and Lambda in situ hybridization demonstrated kappa light chain predominance. CD3 demonstrates scattered T-cells. Reticulin demonstrated mild grade 1-2* out of 4 fibrosis. CD34 positive cells are less than 5%.
MARROW ASPIRATE Smears:
200 cell differential:
Blasts, 2%
Myeloid precursors, 52%
Erythroid precursors, 24%
Lymphocytes, 10%
Eosinophils, 5%
Plasma cells, 6%
Mast cells, 1%
Myeloid maturation: progressive
Erythroid maturation: progressive
Megakaryocytes: present, rare monolobated forms seen
Stainable Iron: Present, no ringed sideroblasts
Marrow Aspirate Sections: Consistent with marrow biopsy.
Marrow Biopsy Touch Prep: Consistent with marrow biopsy
PERIPHERAL BLOOD Smear:
Lymphopenia in an otherwise morphologically unremarkable specimen.
FLOW CYTOMETRY
DIAGNOSIS: Bone Marrow Aspirate: Clonal abnormal plasma cell population.
NOTE: The patient has a history of MGUS and the specimen is submitted for evaluation of disease. The bone marrow aspirate may contain significant blood contamination and morphology should be used for the bone marrow differential.
97% of the plasma cells (European Myeloma Network gating criteria) are abnormal monoclonal plasma cells expressing dim CD27, bright CD38, CD138 partial CD56, dim CD45, moderate to negative CD20, dim CD81, dim CD126, dim CD200 and intracellular kappa but negative for intracellular lambda, CD19 and CD28. The abnormal plasma cells do not express surface light chains. The B-Cells are polyclonal. The immunophenotypic data correlates with morphology.
% Abnormal Plasma Cells (of total plasma cells): 97%
Plasma cells - % of all nucleated cells: 0.3%
Plasma cells - % of mononuclear nucleated cells: 1.4%
GROSS DESCRIPTION: Viability 93%
I definitely don’t have the critical features you mention above, and I am very grateful you took the time to explain this to me. My story is as follows.
Diagnosed MGUS IGg Kappa in December, 2010 based upon 8% PC aspirate, no chromosome abnormality w/ FISH/Cytogenetics, no amyloid in BMB. Normal abdominal fat pad biopsy.
2nd BM Biopsy in 1/12/2012 reflected 6% PC upon aspirate ; 5%-10 % and 10%-15% in core biopsy (details below) Based upon PC% >10%, with 97% aberrant PC and IgA immunoparesis, reclassified as High Risk SMM per Spanish (PETHEMA) study.
No bone lesions per PET/FDG/CT scan and full spine MRI, but per DEXA interim bone demineralization/beginning of severe osteopenia in femoral neck and lumbar spine, hip is normal.
Zometa IV started October, 2012, every 3 months.
IgG ranging from 1235 – 1365 mg/L; IgA immunoparesis (46 mg/L) IgM normal (95 mg/L)
FLC Kappa steadily increasing from 33.46 – 54.34 mg/L., Lambda 6.34 – 5.9, Ratio 5.278 – 9.21
M-spike has remained steady @ 0.80 G/dL.
Normal Hgb 13.1, Creatitine 0.81. , Albumin 4.5 G/dL.
Lymphopenia (ranging 0.8-1.1)
Foamy Urine/proteinuria, but no Bence Jones M-spike, TP 72 mg/24 hours @100% Albumin @ 3/2011; TP 126 mg/24 hours @ 27% Albumin, 20% Alpha 1, 14% Alpha 2, 30% Beta, 8.7% Gamma 10/2012
55 years old post menopausal (2007), mild night sweats and fatigue.
Hashimoto’s, normal thyroid function. Open angle glaucoma. High cholesterol.
Viral pneumonia 10/1990, strep throat infection w/left tonsil abscess 9/2012, frequent sinus infections.
Constant Neuropathy in hands/lower arms, feet/lower legs started in June, 2009. All neuro (EMG/NCS & Epidermal Nerve Fiber Density Skin Biopsy- no amyloid) and autoimmune serum tests normal.
1/12/2012 BONE MARROW BIOPSY.
DIAGNOSIS: bone marrow biopsy, aspirate and peripheral smear:
- Variably cellular bone marrow with increased atypical Cyclin-D1 positive plasma cells with Kappa light chain predominance
- Maturing trilineage hematopoiesis
- High Risk SMM DIAGNOSIS due to 97% aberrant cells of the 10% “averaged” plasma cells upon flow cytometry coupled with IgA immunoparesis per PETHEMA (Spanish risk progression study)
Comment: The percentage of plasma cells varies within the biopsy: some area have 5-10% plasma cells while other areas have 10-15% plasma cells.
MARROW BIOPSY Sections:
Cellularity is variable ranging from 20-40%, overall 30% cellular.
Megakaryocytes: present, non-dysplastic
M:E ratio 2:1
Immunohistochemical stains:
CD138 immunostain highlights increased plasma cells which vary in concentration within the biopsy; some areas contain 10-15% plasma cells while other areas contain 5-10% plasma cells. The plasma cells are positive for Cyclin D1 and negative for CD 56, CD117 and CD20. Kappa and Lambda immunostains as well as Kappa and Lambda in situ hybridization demonstrated kappa light chain predominance. CD3 demonstrates scattered T-cells. Reticulin demonstrated mild grade 1-2* out of 4 fibrosis. CD34 positive cells are less than 5%.
MARROW ASPIRATE Smears:
200 cell differential:
Blasts, 2%
Myeloid precursors, 52%
Erythroid precursors, 24%
Lymphocytes, 10%
Eosinophils, 5%
Plasma cells, 6%
Mast cells, 1%
Myeloid maturation: progressive
Erythroid maturation: progressive
Megakaryocytes: present, rare monolobated forms seen
Stainable Iron: Present, no ringed sideroblasts
Marrow Aspirate Sections: Consistent with marrow biopsy.
Marrow Biopsy Touch Prep: Consistent with marrow biopsy
PERIPHERAL BLOOD Smear:
Lymphopenia in an otherwise morphologically unremarkable specimen.
FLOW CYTOMETRY
DIAGNOSIS: Bone Marrow Aspirate: Clonal abnormal plasma cell population.
NOTE: The patient has a history of MGUS and the specimen is submitted for evaluation of disease. The bone marrow aspirate may contain significant blood contamination and morphology should be used for the bone marrow differential.
97% of the plasma cells (European Myeloma Network gating criteria) are abnormal monoclonal plasma cells expressing dim CD27, bright CD38, CD138 partial CD56, dim CD45, moderate to negative CD20, dim CD81, dim CD126, dim CD200 and intracellular kappa but negative for intracellular lambda, CD19 and CD28. The abnormal plasma cells do not express surface light chains. The B-Cells are polyclonal. The immunophenotypic data correlates with morphology.
% Abnormal Plasma Cells (of total plasma cells): 97%
Plasma cells - % of all nucleated cells: 0.3%
Plasma cells - % of mononuclear nucleated cells: 1.4%
GROSS DESCRIPTION: Viability 93%
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DanaH - Who do you know with myeloma?: Myself, SMM as of 1/2012
- When were you/they diagnosed?: 1/2012
- Age at diagnosis: 54
Re: Would you consider treatment for High Risk Smoldering mu
Hi Dana H, I am currently in the CRD trial at the NIH for newly diagnosed. I was in Dr. Landgren's SMM study at the time I progressed to active myeloma in April, 2012. It is basically the same protocol as the NIH SMM trial. I "smoldered" for 8 months and when I progressed my hemoglobin dropped like a stone, my FLC's exploded and I had a pulmonary embolism. At the time, I was already monitored by the NIH and at UPenn. I decided to try the NIH route. I just wanted to do something different and I liked Dr. Landgren's approach. I live near Philadelphia in NJ and it is about a 2.5 hr. drive for me to Bethesda, MD. I did that 3 times a month for 8 months and now I am on maintenance. For me, the regimen was tolerable, especially after my blood counts came roaring back....they are now all normal and I am doing very well as are, to my knowledge, most of my compatriots in the trial. I was able to work the whole time but, as I indicated, it became more tolerable after my blood counts, especially hemoglobin, came back to normal. When I started the trial my hemoglobin was 8.8....pretty low for a formerly active 50 year old guy. In only a couple months of CRD, it was in the 14's and last month it was 16.4. Anyway, good luck and contact me if you need more info. Terry L.
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terryl1 - Name: Terry
- Who do you know with myeloma?: self
- When were you/they diagnosed?: August 10, 2011
- Age at diagnosis: 49
Re: Would you consider treatment for High Risk Smoldering mu
Hi Terryl1,
I just realized I never responded to your very thoughtful and informative post, so a belated thank you. I am so very happy to hear the NIH Crd trial has been so successful for you and wish you continued positive results. I am contemplating a few choices re 2nd opinions, so hopefully I can determine where I truly fall within the multiple myeloma spectrum...High Risk SMM or Intermediate SMM, that is my question right now...once I achieve my "label", I can figure out my next choices/decisions that I will need to focus on. Thanks for the offer of help, I will most likely be reaching out again.
Best to you.
Dana H.
I just realized I never responded to your very thoughtful and informative post, so a belated thank you. I am so very happy to hear the NIH Crd trial has been so successful for you and wish you continued positive results. I am contemplating a few choices re 2nd opinions, so hopefully I can determine where I truly fall within the multiple myeloma spectrum...High Risk SMM or Intermediate SMM, that is my question right now...once I achieve my "label", I can figure out my next choices/decisions that I will need to focus on. Thanks for the offer of help, I will most likely be reaching out again.
Best to you.
Dana H.
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DanaH - Who do you know with myeloma?: Myself, SMM as of 1/2012
- When were you/they diagnosed?: 1/2012
- Age at diagnosis: 54
Re: Would you consider treatment for High Risk Smoldering mu
Hi Dana H, good luck whatever you do. Hopefully, you may not need treatment for a while.
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terryl1 - Name: Terry
- Who do you know with myeloma?: self
- When were you/they diagnosed?: August 10, 2011
- Age at diagnosis: 49
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