These early phase test results just came out. I'm not sure if the CVDD cocktail has been discussed much in the Beacon before, but this combo has pretty respectable median PFS stats for newly diagnosed patients, albeit the sample population is pretty small and these are only early trial results.
T Nishihori et al, "An open label phase I/II study of cyclophosphamide, bortezomib, pegylated liposomal doxorubicin and dexamethasone in newly diagnosed myeloma," European Journal of Haematology, 2015 (abstract)
Abstract:
We conducted a phase 1/2 trial evaluating the combination of cyclophosphamide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone (CVDD) for newly diagnosed multiple myeloma (multiple myeloma). The primary objective of the phase 1 was to evaluate the safety and tolerability of maximum planned dose (MPD) and the phase 2 was to assess the overall response rate.
Patients received 6-8 cycles of CVDD at 4 dose levels. There were no dose-limiting toxicities. The MPD was cyclophosphamide 750 mg/m2 IV on day 1, bortezomib 1.3 mg/m2 IV on days 1, 4, 8, 11, pegylated liposomal doxorubicin 30 mg/m2 IV on day 4, and dexamethasone 20 mg orally on the day of and after bortezomib (21-day cycle).
Forty nine patients were treated at the MPD, of which 22% had high-risk myeloma. The most common grade ≥3 toxicities included myelosuppression, infection and fatigue.Overall response and complete response rates were 91% and 26% in standard-risk, and 100% and 58% in high-risk cohort, respectively. After a median follow-up of 34 months, the median progression-free survival was 31.3 months. The 2-year overall survival was 91.1% in the standard-risk and 88.9% in the high-risk cohort, respectively.
CVDD regimen was well tolerated and was highly active in newly diagnosed multiple myeloma.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: CVDD in newly diagnosed multiple myeloma - trial results
I found this interesting:
"Overall response and complete response rates were 91% and 26% in standard-risk, and 100% and 58% in high-risk cohort, respectively." In the study 22% of the patients were high risk."
It is very unusual that high-risk patients results are better than standard risk. I wonder if they got the numbers backwards.
The results are no better than what a similar study found with newly diagnosed patients taking VRD. In the older VRD study, 100% of the patients had at least a partial response and 67% had a VGPR or better.
PG Richardson et al, "Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma," Blood, Aug 5, 2010 (full text).
Abstract:
This phase 1/2 study is the first prospective evaluation of lenalidomide-bortezomib-dexamethasone in front-line myeloma. Patients (N = 66) received 3-week cycles (n = 8) of bortezomib 1.0 or 1.3 mg/m2 (days 1, 4, 8, 11), lenalidomide 15 to 25 mg (days 1-14), and dexamethasone 40 or 20 mg (days 1, 2, 4, 5, 8, 9, 11, 12). Responding patients proceeded to maintenance or transplantation. Phase 2 dosing was determined to be bortezomib 1.3 mg/m2, lenalidomide 25 mg, and dexamethasone 20 mg.
Most common toxicities included sensory neuropathy (80%) and fatigue (64%), with only 27%/2% and 32%/3% grade 2/3, respectively. In addition, 32% reported neuropathic pain (11%/3%, grade 2/3). Grade 3/4 hematologic toxicities included lymphopenia (14%), neutropenia (9%), and thrombocytopenia (6%). Thrombosis was rare (6% overall), and no treatment-related mortality was observed.
Rate of partial response was 100% in both the phase 2 population and overall, with 74% and 67% each achieving very good partial response or better. Twenty-eight patients (42%) proceeded to undergo transplantation. With median follow-up of 21 months, estimated 18-month progression-free and overall survival for the combination treatment with / without transplantation were 75% and 97%, respectively.
Lenalidomide-bortezomib-dexamethasone demonstrates favorable tolerability and is highly effective in the treatment of newly diagnosed myeloma.
"Overall response and complete response rates were 91% and 26% in standard-risk, and 100% and 58% in high-risk cohort, respectively." In the study 22% of the patients were high risk."
It is very unusual that high-risk patients results are better than standard risk. I wonder if they got the numbers backwards.
The results are no better than what a similar study found with newly diagnosed patients taking VRD. In the older VRD study, 100% of the patients had at least a partial response and 67% had a VGPR or better.
PG Richardson et al, "Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma," Blood, Aug 5, 2010 (full text).
Abstract:
This phase 1/2 study is the first prospective evaluation of lenalidomide-bortezomib-dexamethasone in front-line myeloma. Patients (N = 66) received 3-week cycles (n = 8) of bortezomib 1.0 or 1.3 mg/m2 (days 1, 4, 8, 11), lenalidomide 15 to 25 mg (days 1-14), and dexamethasone 40 or 20 mg (days 1, 2, 4, 5, 8, 9, 11, 12). Responding patients proceeded to maintenance or transplantation. Phase 2 dosing was determined to be bortezomib 1.3 mg/m2, lenalidomide 25 mg, and dexamethasone 20 mg.
Most common toxicities included sensory neuropathy (80%) and fatigue (64%), with only 27%/2% and 32%/3% grade 2/3, respectively. In addition, 32% reported neuropathic pain (11%/3%, grade 2/3). Grade 3/4 hematologic toxicities included lymphopenia (14%), neutropenia (9%), and thrombocytopenia (6%). Thrombosis was rare (6% overall), and no treatment-related mortality was observed.
Rate of partial response was 100% in both the phase 2 population and overall, with 74% and 67% each achieving very good partial response or better. Twenty-eight patients (42%) proceeded to undergo transplantation. With median follow-up of 21 months, estimated 18-month progression-free and overall survival for the combination treatment with / without transplantation were 75% and 97%, respectively.
Lenalidomide-bortezomib-dexamethasone demonstrates favorable tolerability and is highly effective in the treatment of newly diagnosed myeloma.
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: CVDD in newly diagnosed multiple myeloma - trial results
Thanks, Ron Harvot and Multibilly!
I am hoping to be at 'CR levels' by the end of my third 4-week cycle of RVD.
My protein (all leaking into the urine) in my spot urine sample and the protein/craetinine ratio, both down into the normal range from 200 and 2.0, respectively, to 9.8 and 0.1, already in 4 weeks and 4 days of my induction chemo. This data is very helpful for my own reference.
Ron's reference to the article related to my specific treatment may be more appropriate for me to draw some conclusions from. And I, too, agree that there may be a typo in the "overall response " sentence.
K_Shash
I am hoping to be at 'CR levels' by the end of my third 4-week cycle of RVD.
My protein (all leaking into the urine) in my spot urine sample and the protein/craetinine ratio, both down into the normal range from 200 and 2.0, respectively, to 9.8 and 0.1, already in 4 weeks and 4 days of my induction chemo. This data is very helpful for my own reference.
Ron's reference to the article related to my specific treatment may be more appropriate for me to draw some conclusions from. And I, too, agree that there may be a typo in the "overall response " sentence.
K_Shash
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K_Shash - Name: K_Shash
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: November 2014
- Age at diagnosis: 67
Re: CVDD in newly diagnosed multiple myeloma - trial results
Hi Ron H,
I hope all is well with you.
I do not think it is unusual for high risk patients to have a higher CR rate than standard risk patients. When doctors refer to "high risk" they are usually referring to how long the initial response will likely last. One of the groups that has poor outcomes in myeloma are patients that get a CR and than lose it within 3 years or less.
This study had short term (2 year) follow up. Studies with such short term follow up cannot tell you much about long term outcomes for the patients. This study is actually one of the few that discusses high risk patients which I view as a positive thing. It also does not mean much to compare two short term Phase 2 studies like this one and the VRD study you mention. There could be major differences in the groups of patients and both studies are much shorter than the survival of a typical myeloma patient that would be diagnosed in 2015.
I was a high risk patient at diagnosis and all 3 of the doctors I consulted with were confident I would get to CR. They were also confident I would lose my CR in 12-20 months using only novel agents for maintenance. I used drugs in the same classes as those in the CVDD study and I got to CR so I am not surprised to see a 58% CR rate for the high risk group.
Mark
I hope all is well with you.
I do not think it is unusual for high risk patients to have a higher CR rate than standard risk patients. When doctors refer to "high risk" they are usually referring to how long the initial response will likely last. One of the groups that has poor outcomes in myeloma are patients that get a CR and than lose it within 3 years or less.
This study had short term (2 year) follow up. Studies with such short term follow up cannot tell you much about long term outcomes for the patients. This study is actually one of the few that discusses high risk patients which I view as a positive thing. It also does not mean much to compare two short term Phase 2 studies like this one and the VRD study you mention. There could be major differences in the groups of patients and both studies are much shorter than the survival of a typical myeloma patient that would be diagnosed in 2015.
I was a high risk patient at diagnosis and all 3 of the doctors I consulted with were confident I would get to CR. They were also confident I would lose my CR in 12-20 months using only novel agents for maintenance. I used drugs in the same classes as those in the CVDD study and I got to CR so I am not surprised to see a 58% CR rate for the high risk group.
Mark
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Mark11
Re: CVDD in newly diagnosed multiple myeloma - trial results
Thanks for the follow up Mark. I was wondering about the high risk response rate as well and was glad that Ron brought it up.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: CVDD in newly diagnosed multiple myeloma - trial results
Hi Mark 11,
In your post, you made reference to survival of a typical myeloma patient diagnosed in 2015. Would you be able to expand on that a little? The only survival rates I have seen so far are from the American Cancer Society, which shows median survival rates of 29 months (Stage 3) to 62 months (Stage 1).
I realize they are talking about median (middle) values, and that the high and low could be very far away. Still, that does not seem so great to me, and it would be nice to see something better. I am not sure how recent those stats are, but the web page says last revised January 23, 2015. I just got diagnosed with multiple myeloma earlier this month.
Thanks, Mike
In your post, you made reference to survival of a typical myeloma patient diagnosed in 2015. Would you be able to expand on that a little? The only survival rates I have seen so far are from the American Cancer Society, which shows median survival rates of 29 months (Stage 3) to 62 months (Stage 1).
I realize they are talking about median (middle) values, and that the high and low could be very far away. Still, that does not seem so great to me, and it would be nice to see something better. I am not sure how recent those stats are, but the web page says last revised January 23, 2015. I just got diagnosed with multiple myeloma earlier this month.
Thanks, Mike
Re: CVDD in newly diagnosed multiple myeloma - trial results
Hi Mike,
Any patient's prognosis will vary due to a variety of factors. General statistics like those may or may not apply to a particular patient. For example, the average age of a myeloma patient is 70. That means a decent percentage are elderly, frail patients with significant comorbidities. A younger healthier patient is likely to live longer. In a recent paper discussing maintenance therapy, Dr. Rajkumar of Mayo wrote that younger standard patients are close to 10 years.
"In fact, indefinite maintenance until disease progression virtually ensures continuous lifelong drug therapy for myeloma patients, at a time when median survival for younger standard-risk patients is approaching > 10 years."
Dr. Rajkumar also mentions another major factor - disease biology. It appears there are multiple types of myeloma. The disease behaves very differently depending on the person.
IMO it is best for each patient to discuss their individual prognosis with a specialist or ideally multiple specialists as opposed to relying on statistics about the "average" patient.
Mark
Any patient's prognosis will vary due to a variety of factors. General statistics like those may or may not apply to a particular patient. For example, the average age of a myeloma patient is 70. That means a decent percentage are elderly, frail patients with significant comorbidities. A younger healthier patient is likely to live longer. In a recent paper discussing maintenance therapy, Dr. Rajkumar of Mayo wrote that younger standard patients are close to 10 years.
"In fact, indefinite maintenance until disease progression virtually ensures continuous lifelong drug therapy for myeloma patients, at a time when median survival for younger standard-risk patients is approaching > 10 years."
Dr. Rajkumar also mentions another major factor - disease biology. It appears there are multiple types of myeloma. The disease behaves very differently depending on the person.
IMO it is best for each patient to discuss their individual prognosis with a specialist or ideally multiple specialists as opposed to relying on statistics about the "average" patient.
Mark
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Mark11
Re: CVDD in newly diagnosed multiple myeloma - trial results
Mark
Thx for posting this article, it is definitely a step in the right direction. After reading it things dont seem as bad!
Mike
Thx for posting this article, it is definitely a step in the right direction. After reading it things dont seem as bad!
Mike
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