I was hoping someone here could comment on this study about Revlimid (lenalidomide) and Dex. It was administered to newly diagnosed patients, It shows that the Rev/DEX combo actually increases the number of myeloid-derived suppressor cells (MDSCs) after 4 cycles. HV's are healthy volunteers.
"Background. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous
population of immature cells and reported to be expanded in pathological conditions
including cancer, infectious diseases and some autoimmune diseases.
Recently, a large number of studies showed MDSCs expansion and their suppressive
function in tumor models and non-hematological malignancies. Multiple
myeloma (multiple myeloma) is a plasma cell malignancy associated with immunological
impairments. Aims. To evaluate frequency of MDSCs and their suppressive
function in multiple myeloma patients at baseline and after lenalidomide plus dexamethasone
(LD) treatment."
Results. MDSCs were identified as
CD33+CD11b+CD14-HLADR-. Frequency of MDSCs was significantly
increased and total lymphocytes were reduced in multiple myeloma patients at baseline compared
to HVs (median% of MDSCs, 0.33 vs.0.08; P=0.001 and median% of
lymphocytes, 16.10 vs. 36.13; P=0.01). However, baseline CD4 and CD8 T cells from multiple myeloma patients did not differ significantly from HVs. When we compared
MDSCs from baseline and post-LD treatment, significant increase was observed
after the 4th cycle but similar frequency was observed after 1-3 cycles (median%
of MDSCs, 0.33 vs. 0.57; P=0.033).
"Our findings suggest that MDSCs are expanded and functional in multiple myeloma.
LD treatment in multiple myeloma did not reduce MDSCs and their suppressive function.
Expansion of these cells might enhance immune suppression in multiple myeloma and thereby
progress the disease."
http://www.ehaweb.org/science/scientific-library/abstract-book/
The study I am referring to is on page 110 of the 2012 Abstract Book.
Since patients had increased numbers of MDSC's after the 4th cycle of Rev/DEX, would this study be an arguement against long cycles of Rev/Dex? I have never used Revlimid but it may be part of my therapy with DLI's if I ever lost my molecular response. Since I did an allo as part of my upfront therapy the role of the immune system in myeloma is of great interest to me.
Thanks,
Mark
Forums
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• Page 1 of 1
Re: Interesting Study on Revlimid and Dex
Hi Mark!
I am unable to get to page 10 in the Abstract Book. The link you provided only goes to the page that says Abstract Book, but does not allow browsing of the book.
From the data you provided, it appears that the elevated MDSC's post 4th cycle could be a mechanism for chemo resistance.
I am unable to get to page 10 in the Abstract Book. The link you provided only goes to the page that says Abstract Book, but does not allow browsing of the book.
From the data you provided, it appears that the elevated MDSC's post 4th cycle could be a mechanism for chemo resistance.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Interesting Study on Revlimid and Dex
Suzierose,
Hope all is good with you. I saved the Abstract Book. They had it set up where you could search terms but unfortunately they took it down and put up the extract book. You have a scientific background, so you would understand this a lot more than me. There were a couple of extracts speaking about myeloid-derived suppressor cells. I am guessing it is the DEX causing this since it is so immunosuppressive. Here is the whole abstract. What I took out of it was how the MDSC's do not start increasing until after 3 cycles of Revlimid/DEX. Maybe 8 cycles of Revlimid/DEX for Induction is not such a great idea?
FUNCTIONALLY ACTIVE MYELOID-DERIVED SUPPRESSOR CELLS ARE
INCREASED AFTER LENALIDOMIDE PLUS DEXAMETHASONE TREATMENT
IN PREVIOUSLY UNTREATED MULTIPLE MYELOMA PATIENTS
K Muthu Raja1, L Rihova2, R Hajek3
1Masaryk University, Brno, Czech Republic
2Dept. of Clinical Hematology, University Hospital, Brno, Czech Republic
3Dept. of Internal Medicine, Hematooncology, University Hospital, Brno, Czech
Republic
Background. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous
population of immature cells and reported to be expanded in pathological conditions
including cancer, infectious diseases and some autoimmune diseases.
Recently, a large number of studies showed MDSCs expansion and their suppressive
function in tumor models and non-hematological malignancies. Multiple
myeloma (multiple myeloma) is a plasma cell malignancy associated with immunological
impairments.
Aims. To evaluate frequency of MDSCs and their suppressive
function in multiple myeloma patients at baseline and after lenalidomide plus dexamethasone
(LD) treatment. Patients and Methods. A cohort of 16 untreated multiple myeloma patients
was included after obtaining signed informed consent forms according to Helsinki
declaration. Median age of the studied cohort was 60 years (range, 36-67).
According to international staging system (ISS) patients were staged as: ISS1,
8/16 (50%); ISS2, 5/16 (31%); and ISS3, 3/16 (19%). All patients received LD
for 4 cycles as induction therapy (lenalidomide, 25mg on days 1-21; dexamethasone,
40mg on days 1, 8, 15, 22). Using multi-parameter flow cytometry (CD4-
FITC, CD11b-PE, CD33-PerCpCy5.5, CD14-PECy7, HLA-DR-APC and CD8-
PB), we assessed MDSCs, total lymphocytes, CD4 and CD8 T cells from PB of
multiple myeloma patients at baseline and after each LD treatment cycle. As controls, 11
healthy volunteers (HVs) PB samples were also assessed. Functional activity
of MDSCs was studied using CFSE based T cell proliferation assays from 4 multiple myeloma
patients (3 untreated and 1 LD treated) and 3 HVs. Further, we profiled supernatants
from proliferation assays for pro-inflammatory (IFN-γ, TNF-α) and
immunosuppressive (IL-10) cytokines.
Results. MDSCs were identified as
CD33+CD11b+CD14-HLADR-. Frequency of MDSCs was significantly
increased and total lymphocytes were reduced in multiple myeloma patients at baseline compared
to HVs (median% of MDSCs, 0.33 vs.0.08; P=0.001 and median% of
lymphocytes, 16.10 vs. 36.13; P=0.01). However, baseline CD4 and CD8 T
cells from multiple myeloma patients did not differ significantly from HVs.
When we compared
MDSCs from baseline and post-LD treatment, significant increase was observed
after the 4th cycle but similar frequency was observed after 1-3 cycles (median%
of MDSCs, 0.33 vs. 0.57; P=0.033).
Functional studies revealed that
MDSCs from multiple myeloma patients and HVs suppressed CD3 T cell proliferation in concentration
dependent manner (1:1, 1:5, 0:1). Suppressive function of MDSCs
was comparable between HVs, untreated and LD treated patients. Cytokine
data from multiple myeloma and HVs showed that in the presence of MDSCs in proliferation
assays, the level of IFN-γ, TNF-α and IL-10 was reduced significantly compared
to proliferation assays without MDSCs (P=0.05). Comparison of multiple myeloma and HVs
cytokine data from proliferation assays (in presence or absence of MDSCs)
showed no significant difference in the level of IFN-γ and TNF-α. But IL-10 level
was 3-fold increased in proliferation assays (without MDSCs) from multiple myeloma
patients compared to HVs (mean pg/ml: 960.88 vs. 368.36; P=0.045).
Conclusions.
Our findings suggest that MDSCs are expanded and functional in multiple myeloma.
LD treatment in multiple myeloma did not reduce MDSCs and their suppressive function.
Expansion of these cells might enhance immune suppression in multiple myeloma and thereby
progress the disease.
Mark
Hope all is good with you. I saved the Abstract Book. They had it set up where you could search terms but unfortunately they took it down and put up the extract book. You have a scientific background, so you would understand this a lot more than me. There were a couple of extracts speaking about myeloid-derived suppressor cells. I am guessing it is the DEX causing this since it is so immunosuppressive. Here is the whole abstract. What I took out of it was how the MDSC's do not start increasing until after 3 cycles of Revlimid/DEX. Maybe 8 cycles of Revlimid/DEX for Induction is not such a great idea?
FUNCTIONALLY ACTIVE MYELOID-DERIVED SUPPRESSOR CELLS ARE
INCREASED AFTER LENALIDOMIDE PLUS DEXAMETHASONE TREATMENT
IN PREVIOUSLY UNTREATED MULTIPLE MYELOMA PATIENTS
K Muthu Raja1, L Rihova2, R Hajek3
1Masaryk University, Brno, Czech Republic
2Dept. of Clinical Hematology, University Hospital, Brno, Czech Republic
3Dept. of Internal Medicine, Hematooncology, University Hospital, Brno, Czech
Republic
Background. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous
population of immature cells and reported to be expanded in pathological conditions
including cancer, infectious diseases and some autoimmune diseases.
Recently, a large number of studies showed MDSCs expansion and their suppressive
function in tumor models and non-hematological malignancies. Multiple
myeloma (multiple myeloma) is a plasma cell malignancy associated with immunological
impairments.
Aims. To evaluate frequency of MDSCs and their suppressive
function in multiple myeloma patients at baseline and after lenalidomide plus dexamethasone
(LD) treatment. Patients and Methods. A cohort of 16 untreated multiple myeloma patients
was included after obtaining signed informed consent forms according to Helsinki
declaration. Median age of the studied cohort was 60 years (range, 36-67).
According to international staging system (ISS) patients were staged as: ISS1,
8/16 (50%); ISS2, 5/16 (31%); and ISS3, 3/16 (19%). All patients received LD
for 4 cycles as induction therapy (lenalidomide, 25mg on days 1-21; dexamethasone,
40mg on days 1, 8, 15, 22). Using multi-parameter flow cytometry (CD4-
FITC, CD11b-PE, CD33-PerCpCy5.5, CD14-PECy7, HLA-DR-APC and CD8-
PB), we assessed MDSCs, total lymphocytes, CD4 and CD8 T cells from PB of
multiple myeloma patients at baseline and after each LD treatment cycle. As controls, 11
healthy volunteers (HVs) PB samples were also assessed. Functional activity
of MDSCs was studied using CFSE based T cell proliferation assays from 4 multiple myeloma
patients (3 untreated and 1 LD treated) and 3 HVs. Further, we profiled supernatants
from proliferation assays for pro-inflammatory (IFN-γ, TNF-α) and
immunosuppressive (IL-10) cytokines.
Results. MDSCs were identified as
CD33+CD11b+CD14-HLADR-. Frequency of MDSCs was significantly
increased and total lymphocytes were reduced in multiple myeloma patients at baseline compared
to HVs (median% of MDSCs, 0.33 vs.0.08; P=0.001 and median% of
lymphocytes, 16.10 vs. 36.13; P=0.01). However, baseline CD4 and CD8 T
cells from multiple myeloma patients did not differ significantly from HVs.
When we compared
MDSCs from baseline and post-LD treatment, significant increase was observed
after the 4th cycle but similar frequency was observed after 1-3 cycles (median%
of MDSCs, 0.33 vs. 0.57; P=0.033).
Functional studies revealed that
MDSCs from multiple myeloma patients and HVs suppressed CD3 T cell proliferation in concentration
dependent manner (1:1, 1:5, 0:1). Suppressive function of MDSCs
was comparable between HVs, untreated and LD treated patients. Cytokine
data from multiple myeloma and HVs showed that in the presence of MDSCs in proliferation
assays, the level of IFN-γ, TNF-α and IL-10 was reduced significantly compared
to proliferation assays without MDSCs (P=0.05). Comparison of multiple myeloma and HVs
cytokine data from proliferation assays (in presence or absence of MDSCs)
showed no significant difference in the level of IFN-γ and TNF-α. But IL-10 level
was 3-fold increased in proliferation assays (without MDSCs) from multiple myeloma
patients compared to HVs (mean pg/ml: 960.88 vs. 368.36; P=0.045).
Conclusions.
Our findings suggest that MDSCs are expanded and functional in multiple myeloma.
LD treatment in multiple myeloma did not reduce MDSCs and their suppressive function.
Expansion of these cells might enhance immune suppression in multiple myeloma and thereby
progress the disease.
Mark
-
Mark
Re: Interesting Study on Revlimid and Dex
currently on the Revlimid and Dex Trial!
I am under 50 years old and am taking Revlimid 25mg per day for cycles of chemotherapy. My regime for igg Multiple Myeloma is RCD. I am on a drugs trial and have completed 3 cycles out of 4 going upto a maximum of 6 depending on the outcome. I hope to have an auto stem cell transplant.
I had real problems with my temperature and chills to start with and ended up in hospital 4 times that were all excessive temperature related incidents. The hospital kept looking for a mystery infection however I believed it was down to the Revlimid. I checked the side effects on the information sheet supplied by the manufacturer and found I had some of the others: the bleeding nose, low white cell count, platelet issues etc. I actually discovered that thel dose of Dex steroid they were giving me was apparently too low. I read the manufacturers recommendations re the dose of Dex linked with the Revlimid usage and mentioned this to the doctors.
They now give me the manufacturers recommended dose of Dex and I have had no temperature issues since the dose was corrected. I notice in some internet information that in trials as many as 76% of those people involved had to have their Revlimid ‘play’ around with dose to get it right for them, I don’t know how accurate this figure is as there is a wealth of information online.
My problem was that I am on a trial so we are all given the same medication irrespective of size. I sometimes think that the Doctors become so obsessed with these trials that they forget that it is the interest of the patient that comes first and not becoming obsessed with following the strict trial rules.
The Revlimid is quite remarkable I had a reading of 53 for the ‘nasty’ para protein in the blood after nearly three cycles this is down to 24. After just two weeks into the first cycle it shrank a tumour in my spine that was almost touching my spinal chord enabling Radiotherapy to ‘finish it off!’.
I am not saying it is for everyone but it is an option like most things it works for some people and not others to varying degrees. I am lucky, so far so good as they say. With regular weekly monitoring of blood any fluctuations should be able to be ironed out with remedial action. This is what they have done for me in the past. It is however from my experience essential to work out the best dose for you’re your own benefit.
If you read the side effects on many regularly taken medications that you probably keep in the family drugs cabinet you would be in two minds whether to take any of them so some perspective is required. Good Luck with any decision you make re Revlimid, I had to think long and hard before I decided to go on the trial and good luck with your futures.
I am under 50 years old and am taking Revlimid 25mg per day for cycles of chemotherapy. My regime for igg Multiple Myeloma is RCD. I am on a drugs trial and have completed 3 cycles out of 4 going upto a maximum of 6 depending on the outcome. I hope to have an auto stem cell transplant.
I had real problems with my temperature and chills to start with and ended up in hospital 4 times that were all excessive temperature related incidents. The hospital kept looking for a mystery infection however I believed it was down to the Revlimid. I checked the side effects on the information sheet supplied by the manufacturer and found I had some of the others: the bleeding nose, low white cell count, platelet issues etc. I actually discovered that thel dose of Dex steroid they were giving me was apparently too low. I read the manufacturers recommendations re the dose of Dex linked with the Revlimid usage and mentioned this to the doctors.
They now give me the manufacturers recommended dose of Dex and I have had no temperature issues since the dose was corrected. I notice in some internet information that in trials as many as 76% of those people involved had to have their Revlimid ‘play’ around with dose to get it right for them, I don’t know how accurate this figure is as there is a wealth of information online.
My problem was that I am on a trial so we are all given the same medication irrespective of size. I sometimes think that the Doctors become so obsessed with these trials that they forget that it is the interest of the patient that comes first and not becoming obsessed with following the strict trial rules.
The Revlimid is quite remarkable I had a reading of 53 for the ‘nasty’ para protein in the blood after nearly three cycles this is down to 24. After just two weeks into the first cycle it shrank a tumour in my spine that was almost touching my spinal chord enabling Radiotherapy to ‘finish it off!’.
I am not saying it is for everyone but it is an option like most things it works for some people and not others to varying degrees. I am lucky, so far so good as they say. With regular weekly monitoring of blood any fluctuations should be able to be ironed out with remedial action. This is what they have done for me in the past. It is however from my experience essential to work out the best dose for you’re your own benefit.
If you read the side effects on many regularly taken medications that you probably keep in the family drugs cabinet you would be in two minds whether to take any of them so some perspective is required. Good Luck with any decision you make re Revlimid, I had to think long and hard before I decided to go on the trial and good luck with your futures.
-
artin888
4 posts
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