Very interesting article on an analysis of patients likely to respond well to Revlimid treatment.
Bottom line is that it appears that newly diagnosed multiple myeloma patients that present with bone disease and have normal kidney function, while being trisomic, are more likely to respond very well to the Revlimid-dexamethasone treatment regimen.
T Vu et al, "Characteristics of exceptional responders to lenalidomide-based therapy in multiple myeloma," Blood Cancer Journal, Oct 23 2015 (full text of article)
Abstract:
We studied all patients at our institution with a diagnosis of multiple myeloma (MM), from 1 January 2004 to 1 July 2009, who received lenalidomide-dexamethasone (Rd) as initial therapy and had a time to progression of 72 months or longer.
Of 240 patients, we identified 33 exceptional responders. Twenty-five patients received primary therapy with Rd and eight patients received Rd induction followed by early stem cell transplantation (SCT). Seven of the eight patients who received SCT did not receive maintenance therapy; one patient received 9 months of lenalidomide post transplant.
Fifteen (45%) patients had known clonal plasma cell disorder before the diagnosis of MM. The dominant mode of clinical presentation was with lytic lesions in 28 patients.
Of those with informative cytogenetics (n=24), trisomies were present in 19 (79%), including one patient with concurrent trisomies and t(11;14). Overall, 21 of 24 patients (88%) had either trisomies or t(11;14). None of these exceptional responders had high-risk cytogenetic features at baseline. Twenty-five patients (76%) had a complete response (CR), whereas eight patients (24%) achieved the exceptional response state without ever achieving a CR.
We identify a cohort of exceptional responders to Rd-based therapy, representing ~10-15% newly diagnosed MM patients with normal renal function.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Revlimid treatment response and trisomies
Multibilly
This is an interesting paper.The patient population included, due to the chosen inclusion criteria,, is small. It would be good if other institutions can confirm the findings.
They do not indicate dosage of Revlimid-dexamethasone in their exceptional responder group, I assume it is the full dose of 25 mg / day for all patients. They do mention different dex dosages.
I wonder if Revlimid-dex might work well on first relapse too in patients with trisomies and clinical features identified for patients who are exceptional responders. If not why not if the disease has not been treated with Revlimid and dex previously?
Edna
This is an interesting paper.The patient population included, due to the chosen inclusion criteria,, is small. It would be good if other institutions can confirm the findings.
They do not indicate dosage of Revlimid-dexamethasone in their exceptional responder group, I assume it is the full dose of 25 mg / day for all patients. They do mention different dex dosages.
I wonder if Revlimid-dex might work well on first relapse too in patients with trisomies and clinical features identified for patients who are exceptional responders. If not why not if the disease has not been treated with Revlimid and dex previously?
Edna
Re: Revlimid treatment response and trisomies
Thanks, Multibilly, for the link to this very interesting paper.
I'm looking forward to discussing this paper with my myeloma specialist when I see him Wednesday for my monthly checkup. He is interested in exceptional responders and has mentioned to me that he thinks a slow response to treatment is sometimes a good thing, as it can be correlated with a long TTP, as shown in this paper. His "theory" on this is that in these cases the disease is more stable - slower to move in either a bad direction or in a good direction. That fits with the interpretation the authors of this paper have regarding the importance of being diagnosed with an antecedent plasma cell disorder before multiple myeloma.
I found it also very interesting that 25% of these exceptional responders had not achieved CR. That has got to give encouragement to lots of folks who do not reach that depth of response. And it fits with Dr. Rajkumar's 2013 Beacon column, "Should Myeloma Patients Panic If They Do Not Achieve A Complete Response?", advising patients not to panic if they don't achieve CR.
On the other hand, it does seem to go counter to what seems to me to be a trend these days in trying to drive the response to be as deep as possible, getting to MRD negative, if possible.
Edna raised some interesting questions about how reliable the results in this study are, given the small sample size. And how extensible the results might be to other therapies, such as those involving Velcade.
For me personally, this study is very encouraging as my case includes all of the "positive" factors I could possibly have at this point: a prior history of plasma cell disorder, a trisomy, bone disease as the defining event (along with anemia in my case), and a slow time course to deepest response. Maybe I can talk someone into selling me life insurance after all.
Mike
I'm looking forward to discussing this paper with my myeloma specialist when I see him Wednesday for my monthly checkup. He is interested in exceptional responders and has mentioned to me that he thinks a slow response to treatment is sometimes a good thing, as it can be correlated with a long TTP, as shown in this paper. His "theory" on this is that in these cases the disease is more stable - slower to move in either a bad direction or in a good direction. That fits with the interpretation the authors of this paper have regarding the importance of being diagnosed with an antecedent plasma cell disorder before multiple myeloma.
I found it also very interesting that 25% of these exceptional responders had not achieved CR. That has got to give encouragement to lots of folks who do not reach that depth of response. And it fits with Dr. Rajkumar's 2013 Beacon column, "Should Myeloma Patients Panic If They Do Not Achieve A Complete Response?", advising patients not to panic if they don't achieve CR.
On the other hand, it does seem to go counter to what seems to me to be a trend these days in trying to drive the response to be as deep as possible, getting to MRD negative, if possible.
Edna raised some interesting questions about how reliable the results in this study are, given the small sample size. And how extensible the results might be to other therapies, such as those involving Velcade.
For me personally, this study is very encouraging as my case includes all of the "positive" factors I could possibly have at this point: a prior history of plasma cell disorder, a trisomy, bone disease as the defining event (along with anemia in my case), and a slow time course to deepest response. Maybe I can talk someone into selling me life insurance after all.
Mike
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mikeb - Name: mikeb
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 2009 (MGUS at that time)
- Age at diagnosis: 55
Re: Revlimid treatment response and trisomies
I was thinking about this paper some more overnight. There are lots of interesting aspects to the paper (at least interesting to me).
One thing that hit me is the researchers' operational definition of "exceptional responder." For their research here, that's someone who has gone at least 6 years from the time of diagnosis without disease progression. Another way of looking at this is that it essentially means someone who has been in remission for at least 5 years, if you assume it takes someone a year of treatment to get to their deepest response - remembering that the exceptional responders took a longer time than average to reach their deepest level of response.
So what this paper is saying, by that definition, is that someone who is in remission from multiple myeloma for 5 years is an "exceptional responder."
When I thought of it that way, it hit me between the eyes - we have a long way to go to cure multiple myeloma! Comparing breast cancer or prostate cancer for example, 5 year remissions are very common now, not "exceptional."
Mike
One thing that hit me is the researchers' operational definition of "exceptional responder." For their research here, that's someone who has gone at least 6 years from the time of diagnosis without disease progression. Another way of looking at this is that it essentially means someone who has been in remission for at least 5 years, if you assume it takes someone a year of treatment to get to their deepest response - remembering that the exceptional responders took a longer time than average to reach their deepest level of response.
So what this paper is saying, by that definition, is that someone who is in remission from multiple myeloma for 5 years is an "exceptional responder."
When I thought of it that way, it hit me between the eyes - we have a long way to go to cure multiple myeloma! Comparing breast cancer or prostate cancer for example, 5 year remissions are very common now, not "exceptional."
Mike
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mikeb - Name: mikeb
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 2009 (MGUS at that time)
- Age at diagnosis: 55
Re: Revlimid treatment response and trisomies
Thanks for posting the link to this paper. While I agree with MikeB's point that we are not very close to a cure for most myeloma patients (other than allo transplant early / in first complete response for younger patients), in my opinion this paper shows how far we are away from making myeloma a truly chronic disease for most patients. Compare the results of this study to what you see for Gleevec (imatinib) for chronic myeloid leukemia CML patients:
Source: L Kalmanti et al, "Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV," Leukemia, May 2015 (abstract)
The novel agents in myeloma are not even close to performing like Gleevec does for CML and making myeloma a chronic disease for the vast majority of myeloma patients.
Tyrosine kinase inhibitors (TKI) have changed the natural course of chronic myeloid leukemia (CML). With the advent of second-generation TKI safety and efficacy issues have gained interest. The randomized CML - Study IV was used for a long-term evaluation of imatinib (IM). 1503 patients have received IM, 1379 IM monotherapy. After a median observation of 7.1 years, 965 patients (64%) still received IM. At 10 years, progression-free survival was 82%, overall survival 84%, 59% achieved MR(5), 72% MR(4.5), 81% MR(4), 89% major molecular remission and 92% MR(2) (molecular equivalent to complete cytogenetic remission)."
Source: L Kalmanti et al, "Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV," Leukemia, May 2015 (abstract)
The novel agents in myeloma are not even close to performing like Gleevec does for CML and making myeloma a chronic disease for the vast majority of myeloma patients.
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Mark11
Re: Revlimid treatment response and trisomies
The abstract was a good read. I was diagnosed with Stage 3 multiple myeloma in August 2012 and received a mixture that included Revlimid. In February 2013 I had a SCT (my identical twin was the donor) and have been on Revlimid 5 mg for maintenance ever since. My numbers are overall good but variable. Six months after SCT my stage was "complete response". So a very successful 3 years and would agree with the article.
Of five people I've known with multiple myeloma, two of us are doing well, one is in ICU and needs our prayers, and two have lost their battle.
Keep the articles coming.
Of five people I've known with multiple myeloma, two of us are doing well, one is in ICU and needs our prayers, and two have lost their battle.
Keep the articles coming.
Re: Revlimid treatment response and trisomies
Mark 11
Agreed the picture for myeloma being a chronic disease for the vast majority of those living with it is not very encouraging. Scientists should aim to understand what it is about myeloma, compared to e.g. CML or other haematologic malignamcies, that renders it less susceptible to long term control at present. Novel drugs do not work for everyone, it seems to be unpredictable and we are no where nearer to individualised treatments based on GEP fingerprints. I personally cannot see this happening due to cost.
Valentine,
You say out of 5 people you have known with multiple myeloma, two lost the battle and one is in ICU. How long did these three have multiple myeloma before the treatment failed? Were they treated at the same centre? Were there age / other medical issues that differed which might have affected 'losing the battle' with treatment?
Edna
Agreed the picture for myeloma being a chronic disease for the vast majority of those living with it is not very encouraging. Scientists should aim to understand what it is about myeloma, compared to e.g. CML or other haematologic malignamcies, that renders it less susceptible to long term control at present. Novel drugs do not work for everyone, it seems to be unpredictable and we are no where nearer to individualised treatments based on GEP fingerprints. I personally cannot see this happening due to cost.
Valentine,
You say out of 5 people you have known with multiple myeloma, two lost the battle and one is in ICU. How long did these three have multiple myeloma before the treatment failed? Were they treated at the same centre? Were there age / other medical issues that differed which might have affected 'losing the battle' with treatment?
Edna
Re: Revlimid treatment response and trisomies
Edna - The five of us are just passing 3 years. Four of the stem cell transplants were allogeneic with number 5 received umbilical stem cells.
Complications for the two that already passed were respiratory. The one in ICU is graft versus host (GVH) and is moving to hospice.
Complications for the two that already passed were respiratory. The one in ICU is graft versus host (GVH) and is moving to hospice.
Re: Revlimid treatment response and trisomies
Valentine, many thanks for sharing this information, at a difficult time.
I wish you all the best, Edna.
I wish you all the best, Edna.
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