This forum thread can be used to discuss the proceedings of the International Myeloma Workshop that take place on Day 3 (Thursday, May 5) of the conference. Feel free to use this space to highlight interesting abstracts, summarize the presentations as they happen, ask questions, and discuss any relevant topics. Everyone is encouraged to participate.
Feel free to also check out the discussions for Day 1, Day 2, and Day 4.
Forums
Re: IMW 2011 Multiple Myeloma Discussion - Day 3
I'll start the postings about today's sessions a bit out of order. There were several sessions earlier in the day that I'll post about later. Right now, however, I'm going to start some live coverage of an afternoon session about secondary primary cancers, particularly the possibility that Revlimid may be linked to an increased rate of secondary cancers in some patients.
There will be presentations during this session from the lead investigators of the three Revlimid maintenance trials that reported increased rates of secondary cancer at the American Society of Hematology annual meeting this past December. In particular, we'll hear from Dr. Michel Attal, the lead investigator of the IFM trial; Dr. Philip McCarthy, the lead investigator of the CALGB trial; and Dr. Antonio Palumbo, the lead investigator of the MM-015 trial.
After those presentations, there will be additional presentations by Dr. Gareth Morgan and Dr. Ola Landgren, followed by a panel discussion and -- if there's time -- answers to questions from the audience.
So let's start the live coverage ...
The first presentation is by Dr. Michel Attal from the Hopital Purpan in Toulouse, France. He is speaking about the IFM trial and secondary malignancies.
Dr. Attal first describes the rationale for the IFM 2005-02 trial as well as the design of the trial:
614 multiple myeloma patients under the age of 65 years who had recently undergone stem cell transplantation received consolidation therapy with Revlimid, and then were randomized to receive long-term Revlimid maintenance therapy or a placebo.
The study's primary endpoint is progression-free survival (PFS). The first interim analysis was done in December 2009. Data and Safety Monitoring Committee suggested to unblind the trial. It was unblinded in July 2010.
Revlimid dosing was stopped in Jan 2011 due to secondary malignancies. The current analysis was performed April 1, 2011.
The results show that the Revlimid arm definitely provides statistically significant progression free survival benefit.
However, overall survival is not different between the Revlimid and placebo arms. There doesn't even seem to be a trend toward a survival benefit.
Dr Attal is now discussing differences between side effects in the Revlimid and placebo arms. He turns specifically to secondary malignancies. A chart shows that cumulative incidence of secondary malignancies starts to develop after 24 months of treatment.
The researchers looked at a variety of factors to determine which are correlated with, and therefore may be the cause of, secondary cancers. Dexamethasone, cyclophosphamide, etoposide, plus cisplatin (DCEP) treatment plays a role, but is not the only factor. Age seems to have been an issue. Also gender.
They statistically checked when the difference in secondary cancers becomes apparent. It appears to be 24 months.
Conclusions: Maintenance with Revlimid is not cause problems with neuropathy or deep vein thrombosis. The risk of secondary cancer is after 24 months. Revlimid is superior to placebo. Revlimid maintenance reduces the risk of progression by 50 percent. This is true in all patient subgroups. Longer follow up is required.
For results of the IFM trial presented at ASH in December, see this Beacon article: https://myelomabeacon.org/news/2010/12/10/studies-support-revlimid-lenalidomide-maintenance-therapy-for-multiple-myeloma-patients-ash-2010/
For more information about the decision to stop dosing in the IFM trial, see this Beacon article: https://myelomabeacon.org/news/2011/02/05/revlimid-lenalidomide-cancer-controversy-flares/
There will be presentations during this session from the lead investigators of the three Revlimid maintenance trials that reported increased rates of secondary cancer at the American Society of Hematology annual meeting this past December. In particular, we'll hear from Dr. Michel Attal, the lead investigator of the IFM trial; Dr. Philip McCarthy, the lead investigator of the CALGB trial; and Dr. Antonio Palumbo, the lead investigator of the MM-015 trial.
After those presentations, there will be additional presentations by Dr. Gareth Morgan and Dr. Ola Landgren, followed by a panel discussion and -- if there's time -- answers to questions from the audience.
So let's start the live coverage ...
The first presentation is by Dr. Michel Attal from the Hopital Purpan in Toulouse, France. He is speaking about the IFM trial and secondary malignancies.
Dr. Attal first describes the rationale for the IFM 2005-02 trial as well as the design of the trial:
614 multiple myeloma patients under the age of 65 years who had recently undergone stem cell transplantation received consolidation therapy with Revlimid, and then were randomized to receive long-term Revlimid maintenance therapy or a placebo.
The study's primary endpoint is progression-free survival (PFS). The first interim analysis was done in December 2009. Data and Safety Monitoring Committee suggested to unblind the trial. It was unblinded in July 2010.
Revlimid dosing was stopped in Jan 2011 due to secondary malignancies. The current analysis was performed April 1, 2011.
The results show that the Revlimid arm definitely provides statistically significant progression free survival benefit.
However, overall survival is not different between the Revlimid and placebo arms. There doesn't even seem to be a trend toward a survival benefit.
Dr Attal is now discussing differences between side effects in the Revlimid and placebo arms. He turns specifically to secondary malignancies. A chart shows that cumulative incidence of secondary malignancies starts to develop after 24 months of treatment.
The researchers looked at a variety of factors to determine which are correlated with, and therefore may be the cause of, secondary cancers. Dexamethasone, cyclophosphamide, etoposide, plus cisplatin (DCEP) treatment plays a role, but is not the only factor. Age seems to have been an issue. Also gender.
They statistically checked when the difference in secondary cancers becomes apparent. It appears to be 24 months.
Conclusions: Maintenance with Revlimid is not cause problems with neuropathy or deep vein thrombosis. The risk of secondary cancer is after 24 months. Revlimid is superior to placebo. Revlimid maintenance reduces the risk of progression by 50 percent. This is true in all patient subgroups. Longer follow up is required.
For results of the IFM trial presented at ASH in December, see this Beacon article: https://myelomabeacon.org/news/2010/12/10/studies-support-revlimid-lenalidomide-maintenance-therapy-for-multiple-myeloma-patients-ash-2010/
For more information about the decision to stop dosing in the IFM trial, see this Beacon article: https://myelomabeacon.org/news/2011/02/05/revlimid-lenalidomide-cancer-controversy-flares/
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Boris Simkovich - Name: Boris Simkovich
Founder
The Myeloma Beacon
Re: IMW 2011 Multiple Myeloma Discussion - Day 3
Dr. Philip McCarthy from Roswell Park Cancer Center takes the stage to discuss CALGB trial results.
He first describes the design of the trial: 568 multiple myeloma patients under the age of 70 years were randomized to receive either Revlimid maintenance therapy or a placebo following autologous stem cell transplantation.
The primary objective is to test Revlimid maintenance efficacy. Survival is a secondary objective. The study opened in 2005 and accrual was completed in July 2009. Patients continued in the trial until progression.
The participants underwent lots of different induction regimens. Lots.
Side effects during maintenance: Neutropenia is the biggest issue. Also some thrombocytopenia.
Second cancers: 29 new second cancers reported from 568 registered patients. This does not include 5 non-melanoma skin cancers.
Since the imbalance of second cancers were first reported, the researchers have done a second cancer "sweep." No new hematologic cancers have been picked up. Five new solid tumor second cancers have been reported.
Time to progression: 62 percent reduction with Revlimid maintenance therapy.
Overall survival: Results weren't presented in a way that is easy to interpret, but it appears to be a significant (p=0.01 approximately) survival benefit. After more than two years of follow-up time, 90% of patients in the Revlimid arm were still alive compared to 83% of patients in the placebo group.
Conclusions: Revlimid maintenance has a favorable effect on time to progression and survival. There were a few other items I was not able to catch. I expect to get a copy of the presentation and will post it if permitted to.
For results from the CALGB study presented at ASH in December 2010, see this Beacon article: https://myelomabeacon.org/news/2010/12/10/studies-support-revlimid-lenalidomide-maintenance-therapy-for-multiple-myeloma-patients-ash-2010/
For information about the decision to continue dosing in the CALGB study despite more second cancers in the Revlimid arm, see this Beacon article: https://myelomabeacon.org/news/2011/02/06/revlimid-lenalidomide-dosing-to-continue-in-calgb-maintenance-trial/
He first describes the design of the trial: 568 multiple myeloma patients under the age of 70 years were randomized to receive either Revlimid maintenance therapy or a placebo following autologous stem cell transplantation.
The primary objective is to test Revlimid maintenance efficacy. Survival is a secondary objective. The study opened in 2005 and accrual was completed in July 2009. Patients continued in the trial until progression.
The participants underwent lots of different induction regimens. Lots.
Side effects during maintenance: Neutropenia is the biggest issue. Also some thrombocytopenia.
Second cancers: 29 new second cancers reported from 568 registered patients. This does not include 5 non-melanoma skin cancers.
Since the imbalance of second cancers were first reported, the researchers have done a second cancer "sweep." No new hematologic cancers have been picked up. Five new solid tumor second cancers have been reported.
Time to progression: 62 percent reduction with Revlimid maintenance therapy.
Overall survival: Results weren't presented in a way that is easy to interpret, but it appears to be a significant (p=0.01 approximately) survival benefit. After more than two years of follow-up time, 90% of patients in the Revlimid arm were still alive compared to 83% of patients in the placebo group.
Conclusions: Revlimid maintenance has a favorable effect on time to progression and survival. There were a few other items I was not able to catch. I expect to get a copy of the presentation and will post it if permitted to.
For results from the CALGB study presented at ASH in December 2010, see this Beacon article: https://myelomabeacon.org/news/2010/12/10/studies-support-revlimid-lenalidomide-maintenance-therapy-for-multiple-myeloma-patients-ash-2010/
For information about the decision to continue dosing in the CALGB study despite more second cancers in the Revlimid arm, see this Beacon article: https://myelomabeacon.org/news/2011/02/06/revlimid-lenalidomide-dosing-to-continue-in-calgb-maintenance-trial/
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Boris Simkovich - Name: Boris Simkovich
Founder
The Myeloma Beacon
Re: IMW 2011 Multiple Myeloma Discussion - Day 3
Dr. Antonio Palumbo from the University of Torino in Italy takes the stage to update results of the MM-015 trial he has been leading.
He describes the MM-015 study design: The study included 459 patients ages 65 years and older who received one of three possible treatment regimens. One regimen consisted of nine 28-day cycles of melphalan and prednisone alone followed by placebo (MP). The second regimen consisted of nine 28-day cycles of melphalan, prednisone, and Revlimid also followed by placebo (MPR). The third regimen was the same as the second, but, instead of receiving placebo after the first nine cycles of treatment, patients received maintenance therapy with Revlimid (MPR-R).
Dr. Palumbo is now summarizing the results for progression free survival. Revlimid maintenance leads to 60 percent reduction in progression.
Secondary cancers: 8 percent in Revlimid maintenance arm. 5.9 percent in in MPR arm (no Revlimid maintenance). 2.6 percent in arm without any Revlimid. The main difference is between rates of hematologic cancers - there are more in the Revlimid arms.
At the beginning of his talk, he noted that when trial investigators analyze the risk of second cancer, they need to take into account the length of time on therapy.
Then he showed a difference in rates of second cancer per year. He still sees higher rates in the Revlimid arms. I didn't catch the exact numbers.
Then he turns to a retrospective study, the purpose of which was to evaluate the risk of second cancers in 9 trials within the European Myeloma Network. The study includes about 2500 patients. About 1400 patients received Revlimid at some point, but not all were included in the eventual analysis. He now describes the characteristics of patients included in analysis. (It's not clear why some patients were included, while others were not.)
During the retrospective analysis, the researchers found most second cancers occurred during treatment. But there were some cancers that were reported after treatment stopped. This is something to take into account when looking at current trials and reported second cancer rates.
Secondary cancer incidence rates: This retrospective analysis actually shows lower second cancer rates among Revlimid patients compared to all patients analyzed.
Dr. Palumbo also shows a comparison of second cancer rates among Italian patients (I'm not sure which trials this includes -- the ones he just discussed, or MM-015). He compared rates in these trials versus what would be expected from analysis of the Italian cancer registry trial. The second cancer rate in Revlimid patients is lower than expected from the registry.
Conclusions: Longer follow up is needed. At present, observed and expected rates of second cancers are not significantly different from one another.
For results from the MM-015 trial presented at ASH in December, see this Beacon article: https://myelomabeacon.org/news/2010/12/10/studies-support-revlimid-lenalidomide-maintenance-therapy-for-multiple-myeloma-patients-ash-2010/
For information about the decision to continue dosing in the MM-015 trial despite more second cancers in the Revlimid arms, see this Beacon article: https://myelomabeacon.org/news/2011/03/02/revlimid-lenalidomide-dosing-will-continue-in-multiple-myeloma-mm-015-trial/
He describes the MM-015 study design: The study included 459 patients ages 65 years and older who received one of three possible treatment regimens. One regimen consisted of nine 28-day cycles of melphalan and prednisone alone followed by placebo (MP). The second regimen consisted of nine 28-day cycles of melphalan, prednisone, and Revlimid also followed by placebo (MPR). The third regimen was the same as the second, but, instead of receiving placebo after the first nine cycles of treatment, patients received maintenance therapy with Revlimid (MPR-R).
Dr. Palumbo is now summarizing the results for progression free survival. Revlimid maintenance leads to 60 percent reduction in progression.
Secondary cancers: 8 percent in Revlimid maintenance arm. 5.9 percent in in MPR arm (no Revlimid maintenance). 2.6 percent in arm without any Revlimid. The main difference is between rates of hematologic cancers - there are more in the Revlimid arms.
At the beginning of his talk, he noted that when trial investigators analyze the risk of second cancer, they need to take into account the length of time on therapy.
Then he showed a difference in rates of second cancer per year. He still sees higher rates in the Revlimid arms. I didn't catch the exact numbers.
Then he turns to a retrospective study, the purpose of which was to evaluate the risk of second cancers in 9 trials within the European Myeloma Network. The study includes about 2500 patients. About 1400 patients received Revlimid at some point, but not all were included in the eventual analysis. He now describes the characteristics of patients included in analysis. (It's not clear why some patients were included, while others were not.)
During the retrospective analysis, the researchers found most second cancers occurred during treatment. But there were some cancers that were reported after treatment stopped. This is something to take into account when looking at current trials and reported second cancer rates.
Secondary cancer incidence rates: This retrospective analysis actually shows lower second cancer rates among Revlimid patients compared to all patients analyzed.
Dr. Palumbo also shows a comparison of second cancer rates among Italian patients (I'm not sure which trials this includes -- the ones he just discussed, or MM-015). He compared rates in these trials versus what would be expected from analysis of the Italian cancer registry trial. The second cancer rate in Revlimid patients is lower than expected from the registry.
Conclusions: Longer follow up is needed. At present, observed and expected rates of second cancers are not significantly different from one another.
For results from the MM-015 trial presented at ASH in December, see this Beacon article: https://myelomabeacon.org/news/2010/12/10/studies-support-revlimid-lenalidomide-maintenance-therapy-for-multiple-myeloma-patients-ash-2010/
For information about the decision to continue dosing in the MM-015 trial despite more second cancers in the Revlimid arms, see this Beacon article: https://myelomabeacon.org/news/2011/03/02/revlimid-lenalidomide-dosing-will-continue-in-multiple-myeloma-mm-015-trial/
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Boris Simkovich - Name: Boris Simkovich
Founder
The Myeloma Beacon
Re: IMW 2011 Multiple Myeloma Discussion - Day 3
Now Dr. Gareth Morgan from the Royal Marsden Hospital in London will speak. He will look at results of a retrospective analysis of Revlimid safety.
He establishes with SEER data that the background rate of secondary cancer in an age-matched patient population similar to the Revlimid patients is about 2 per 100 patient years.
He then looks at data from several Celgene-sponsored trials. He pools the datasets into one big dataset and calculates the rate of secondary cancer per year. He gets rates that are indistinguishable from the background rate of 2 -- values are in the 1.9 to 2.2 range (roughly).
Dr. Morgan concludes that there is no apparent significant risk of second cancer in Revlimid patients compared to standard risk in a comparable patient population.
He establishes with SEER data that the background rate of secondary cancer in an age-matched patient population similar to the Revlimid patients is about 2 per 100 patient years.
He then looks at data from several Celgene-sponsored trials. He pools the datasets into one big dataset and calculates the rate of secondary cancer per year. He gets rates that are indistinguishable from the background rate of 2 -- values are in the 1.9 to 2.2 range (roughly).
Dr. Morgan concludes that there is no apparent significant risk of second cancer in Revlimid patients compared to standard risk in a comparable patient population.
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Boris Simkovich - Name: Boris Simkovich
Founder
The Myeloma Beacon
Re: IMW 2011 Multiple Myeloma Discussion - Day 3
The final presentation during the session is by Dr. Ola Landgren from the National Cancer Institute and National Institutes of Health in Maryland. He will look at what happens to the risk for second cancers in myeloma patients in Sweden before and after 1995.
He focuses on the incidence of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). He finds no sign of an increase in risk of myeloma patients getting AML or MDS after 1995. However, the data only go to 2006, so we can't really use these data to understand the impact of newer myeloma therapies on the risk of second cancers, including AML and MDS.
He focuses on the incidence of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). He finds no sign of an increase in risk of myeloma patients getting AML or MDS after 1995. However, the data only go to 2006, so we can't really use these data to understand the impact of newer myeloma therapies on the risk of second cancers, including AML and MDS.
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Boris Simkovich - Name: Boris Simkovich
Founder
The Myeloma Beacon
Re: IMW 2011 Multiple Myeloma Discussion - Day 3
A discussion of the previous presentations starts.
First question from the chair of the panel: Does Revlimid increase second cancer incidence rates? Dr. McCarthy is uncertain. Dr. Landgren says he is a little concerned, but is also uncertain. Dr. Morgan says no in relapsed and refractory patients. But perhaps there may be risk in stem cell transplant patients. Dr. Attal agrees with Dr. Morgan. He is certain there is a big benefit to Revlimid maintenance in stem cell patients. But the recent trial data -- involving many patients -- makes him concerned that there is an increased risk in stem cell transplant patients. Dr. Palumbo says the benefit is much greater than the risk, and he is not willing to make judgment even with the number of patients involved in the three trials.
Second question: Should Revlimid maintenance be stopped at some point? Dr. Palumbo says no. Dr. Attal thinks it is too early to make a recomendation; perhaps they will have enough data in one year. The IFM trial made its decision to stop because it was not seeing a survival benefit to Rev maintenance. (All Dr. Attal's comments pertain to patients receiving stem cell transplants.) Dr. Morgan agrees more with Dr. Palumbo. Dr. McCarthy also sides with Dr. Palumbo; he is not willing to stop Revlimid maintenance.
The panel discussion ends.
First question from the chair of the panel: Does Revlimid increase second cancer incidence rates? Dr. McCarthy is uncertain. Dr. Landgren says he is a little concerned, but is also uncertain. Dr. Morgan says no in relapsed and refractory patients. But perhaps there may be risk in stem cell transplant patients. Dr. Attal agrees with Dr. Morgan. He is certain there is a big benefit to Revlimid maintenance in stem cell patients. But the recent trial data -- involving many patients -- makes him concerned that there is an increased risk in stem cell transplant patients. Dr. Palumbo says the benefit is much greater than the risk, and he is not willing to make judgment even with the number of patients involved in the three trials.
Second question: Should Revlimid maintenance be stopped at some point? Dr. Palumbo says no. Dr. Attal thinks it is too early to make a recomendation; perhaps they will have enough data in one year. The IFM trial made its decision to stop because it was not seeing a survival benefit to Rev maintenance. (All Dr. Attal's comments pertain to patients receiving stem cell transplants.) Dr. Morgan agrees more with Dr. Palumbo. Dr. McCarthy also sides with Dr. Palumbo; he is not willing to stop Revlimid maintenance.
The panel discussion ends.
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Boris Simkovich - Name: Boris Simkovich
Founder
The Myeloma Beacon
Re: IMW 2011 Multiple Myeloma Discussion - Day 3
I am going to go back now and discuss what happened in the first presentation session today.
The first session focused on the treatment of newly diagnosed myeloma patients over the age of 65. It was the complementary session to the first session yesterday, which focused on the treatment of newly diagnosed patients under the age of 65.
The session also was organized similarly to yesterday's session. There first part of each session was an introductory presentation given by a researcher who, among other things, reviewed relevant clinical trial data, identified key issues, and then shared his own personal treatment preferences.
Following the introductory presentation, individual researchers from a variety of countries discussed what myeloma specialists in their countries see as important open issues related to the treatment of the patient population being discussed. In addition, these presenters also described the new trials underway (or soon to be underway) in their countries that are intended to shed light on the key open issues.
Before I go any further, I should note that, implicit in the purpose of this session was the assumption that the patient population to be discussed is not just newly diagnosed myeloma patients over the age of 65. Instead, it is patients in this group who also are considered not eligible for a stem cell transplant.
That is, the assumption during most of this session was that stem cell transplants are not to be among the treatment options considered for the older newly diagnosed patients under discussion.
The introductory presentation for this session was given by Dr. Vincent Rajkumar of the Mayo Clinic in Minnesota. Dr. Rajkumar, many readers will note, is also a physician columnist at The Beacon. His columns can be viewed here: https://myelomabeacon.org/author/vincent-rajkumar/ .
The first half of Dr. Rajkumar's presentation focused on potential treatments for older newly diagnosed myeloma patients; the clinical trial data relevant to those treatments; and thoughts and comments by Dr. Rajkumar relevant to treating these patients.
The "thoughts and comments" content in this part of the presentation was often particularly interesting.
Dr. Rajkumar make it clear from the outset, for example, that he believes the treatment for an older newly diagnosed patient should be based heavily on the patient's risk classification. Not surprisingly, he favors the risk classification that's been developed at the Mayo Clinic.
Also during this part of the presentation, Dr. Rajkumar mentioned that he is not really a fan of melphalan -- even though it has a long history of use as a myeloma treatment.
A key reason for his not liking melphalan is that he believes it can reduce the efficacy of other treatments a patient may receive after a melphalan-based regimen stops being effective for the patient.
The second half of Dr. Rajkumar's presentation focused on how he, personally, treats older newly diagnosed patients. He explained that he chooses the initial treatment based on whether the patient is standard risk, intermediate risk, or high risk.
In the case of standard risk patients, he recommends treatment with Revlimid and low-dose dexamethasone.
For intermediate-risk patients, he believes Velcade should be part of the treatment regimen, and he prefers a combination regimen involving Velcade, cyclophosphamide, and dexamethasone (VCd or CyBorD).
For high-risk patients, the treatment choice depends partly on a patient's preferences, but Dr. Rajkumar typically uses the combination of Revlimid, Velcade, and dexamethasone (RVd or VRd).
How long does he treat patients with these initial regimens?
Standard risk patients are treated for 18 months and Dr. Rajkumar then discusses with each patient the option of going on to maintenance therapy with Revlimid.
Intermediate risk patients are treated for one year and then put on a Velcade maintenance regimen for two years.
Finally, higher-risk patients are treated as long as it is necessary to (hopefully) achieve complete response, at which point they are put on Velcade maintenance therapy and kept on that therapy as long as it keeps them from progressing.
In just about all cases when Dr. Rajkumar treats a patient with Velcade, he treats them with subcutaneously administered Velcade, rather than infused Velcade, administered once a week. Dr. Rajkumar feels that this method and frequency of administration has shown good efficacy while also reducing the incidence of peripheral neuropathy which, in the past, has been quite common among patients receiving infused, more frequently administered Velcade therapy.
The first session focused on the treatment of newly diagnosed myeloma patients over the age of 65. It was the complementary session to the first session yesterday, which focused on the treatment of newly diagnosed patients under the age of 65.
The session also was organized similarly to yesterday's session. There first part of each session was an introductory presentation given by a researcher who, among other things, reviewed relevant clinical trial data, identified key issues, and then shared his own personal treatment preferences.
Following the introductory presentation, individual researchers from a variety of countries discussed what myeloma specialists in their countries see as important open issues related to the treatment of the patient population being discussed. In addition, these presenters also described the new trials underway (or soon to be underway) in their countries that are intended to shed light on the key open issues.
Before I go any further, I should note that, implicit in the purpose of this session was the assumption that the patient population to be discussed is not just newly diagnosed myeloma patients over the age of 65. Instead, it is patients in this group who also are considered not eligible for a stem cell transplant.
That is, the assumption during most of this session was that stem cell transplants are not to be among the treatment options considered for the older newly diagnosed patients under discussion.
The introductory presentation for this session was given by Dr. Vincent Rajkumar of the Mayo Clinic in Minnesota. Dr. Rajkumar, many readers will note, is also a physician columnist at The Beacon. His columns can be viewed here: https://myelomabeacon.org/author/vincent-rajkumar/ .
The first half of Dr. Rajkumar's presentation focused on potential treatments for older newly diagnosed myeloma patients; the clinical trial data relevant to those treatments; and thoughts and comments by Dr. Rajkumar relevant to treating these patients.
The "thoughts and comments" content in this part of the presentation was often particularly interesting.
Dr. Rajkumar make it clear from the outset, for example, that he believes the treatment for an older newly diagnosed patient should be based heavily on the patient's risk classification. Not surprisingly, he favors the risk classification that's been developed at the Mayo Clinic.
Also during this part of the presentation, Dr. Rajkumar mentioned that he is not really a fan of melphalan -- even though it has a long history of use as a myeloma treatment.
A key reason for his not liking melphalan is that he believes it can reduce the efficacy of other treatments a patient may receive after a melphalan-based regimen stops being effective for the patient.
The second half of Dr. Rajkumar's presentation focused on how he, personally, treats older newly diagnosed patients. He explained that he chooses the initial treatment based on whether the patient is standard risk, intermediate risk, or high risk.
In the case of standard risk patients, he recommends treatment with Revlimid and low-dose dexamethasone.
For intermediate-risk patients, he believes Velcade should be part of the treatment regimen, and he prefers a combination regimen involving Velcade, cyclophosphamide, and dexamethasone (VCd or CyBorD).
For high-risk patients, the treatment choice depends partly on a patient's preferences, but Dr. Rajkumar typically uses the combination of Revlimid, Velcade, and dexamethasone (RVd or VRd).
How long does he treat patients with these initial regimens?
Standard risk patients are treated for 18 months and Dr. Rajkumar then discusses with each patient the option of going on to maintenance therapy with Revlimid.
Intermediate risk patients are treated for one year and then put on a Velcade maintenance regimen for two years.
Finally, higher-risk patients are treated as long as it is necessary to (hopefully) achieve complete response, at which point they are put on Velcade maintenance therapy and kept on that therapy as long as it keeps them from progressing.
In just about all cases when Dr. Rajkumar treats a patient with Velcade, he treats them with subcutaneously administered Velcade, rather than infused Velcade, administered once a week. Dr. Rajkumar feels that this method and frequency of administration has shown good efficacy while also reducing the incidence of peripheral neuropathy which, in the past, has been quite common among patients receiving infused, more frequently administered Velcade therapy.
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Boris Simkovich - Name: Boris Simkovich
Founder
The Myeloma Beacon
Re: IMW 2011 Multiple Myeloma Discussion - Day 3
After Dr. Rajkumar's introductory presentation, individual myeloma researchers from a number of different countries discussed (mainly) the trials that they have started to investigate different potential treatment options for older newly diagnosed myeloma patients.
It would be tedious here to review each and every trial that was discussed during this part of the session. Instead, I'll focus instead on some overarching themes that were visible across the presentation, as well as interesting questions or controversies that became apparent.
The first thing that is readily apparent after hearing all the presentations during this session is that there is an extremely broad range of potential treatment options being considered for older newly diagnosed myeloma patients. Focusing just on upfront therapy and ignoring dose-level variations such as low-dose and high-dose dexamethasone, I counted at least ten different regimens being investigated in the trials that were discussed:
1. Melphalan + prednisone + thalidomide
2. Melphalan + prednisone + Revlimid
3. Melphalan + prednisone + Velcade
4. Melphalan + prednisone + Velcade +thalidomide
5. Cyclophosphamide + thalidomide + dexamethasone
6. Cyclophosphamide + Revlimid + dexamethasone
7. Cyclophosphamide + Velcade + dexamethasone
8. Cyclophosphamide + Velcade + dexamethasone + thalidomide
9. Revlimid + dexamethasone
10. Revlimid + dexamethasone + Velcade
There clearly is a diversity of opinion about how best to treat older newly diagnosed patients! That diversity includes, when one looks closer at the trial designs, different opinions on how important it is to include melphalan in the initial treatment regimen.
Second, many of the trials are making certain to analyze and record patient cytogenetics and, in some cases, bone imaging results. However, it's not clear if this is completely universal across the trials, and few of the trials -- if any -- include protocols that differentiate the treatment of patients based on classification schemes such as the one Dr. Rajkumar says he uses when he treats older newly diagnosed patients.
Third, there were a few creative ideas that were either mentioned during the trial discussions, or explicitly incorporated into the trial designs.
For example, Dr. Antonio Palumbo of the University of Turin, Italy, said that he wonders if trials in the future might want to include a kind of scoring system to determine the treatment dose patients receive. A "standard" patient might be assigned a score of zero and be given the standard dosing. A patient who is older -- say, over 75 years of age -- might be assigned a score of 1, and receive a reduced dose for patients with that score. A patient who is both older and has certain co-existing medical conditions (such as heart problems) might be assigned a score of 2, and receive an even lower dose schedule assigned to that score.
Such an approach would systematize the dosing of the patients within trials.
Another creative approach that was discussed came up in the presentation by Dr. Maria-Victoria Meteos of the University of Salamanca, Spain. She described a trial that is testing an initial therapy that consists of two combination regimens: Melphalan, prednisone, and Velcade ("MPV"); and Revlimid and low-dose dexamethasone ("Rd"). However, the trial not only combines these regimens, but compares two different ways of combining them.
One set of patients will receive the two regimens in sequence - a set number of cycles of MPV therapy first, followed by another set number of cycles of Rd.
Another set of patients, in contrast, will receive the regimens in a staggered way. Each patient first will receive a cycle of MPV; then a cycle of Rd; then another cycle of MPV; and so on.
Meteos and her colleagues believe the staggered approach could yield better results. But they are not certain, so they decided to test it within the trial they designed.
It would be tedious here to review each and every trial that was discussed during this part of the session. Instead, I'll focus instead on some overarching themes that were visible across the presentation, as well as interesting questions or controversies that became apparent.
The first thing that is readily apparent after hearing all the presentations during this session is that there is an extremely broad range of potential treatment options being considered for older newly diagnosed myeloma patients. Focusing just on upfront therapy and ignoring dose-level variations such as low-dose and high-dose dexamethasone, I counted at least ten different regimens being investigated in the trials that were discussed:
1. Melphalan + prednisone + thalidomide
2. Melphalan + prednisone + Revlimid
3. Melphalan + prednisone + Velcade
4. Melphalan + prednisone + Velcade +thalidomide
5. Cyclophosphamide + thalidomide + dexamethasone
6. Cyclophosphamide + Revlimid + dexamethasone
7. Cyclophosphamide + Velcade + dexamethasone
8. Cyclophosphamide + Velcade + dexamethasone + thalidomide
9. Revlimid + dexamethasone
10. Revlimid + dexamethasone + Velcade
There clearly is a diversity of opinion about how best to treat older newly diagnosed patients! That diversity includes, when one looks closer at the trial designs, different opinions on how important it is to include melphalan in the initial treatment regimen.
Second, many of the trials are making certain to analyze and record patient cytogenetics and, in some cases, bone imaging results. However, it's not clear if this is completely universal across the trials, and few of the trials -- if any -- include protocols that differentiate the treatment of patients based on classification schemes such as the one Dr. Rajkumar says he uses when he treats older newly diagnosed patients.
Third, there were a few creative ideas that were either mentioned during the trial discussions, or explicitly incorporated into the trial designs.
For example, Dr. Antonio Palumbo of the University of Turin, Italy, said that he wonders if trials in the future might want to include a kind of scoring system to determine the treatment dose patients receive. A "standard" patient might be assigned a score of zero and be given the standard dosing. A patient who is older -- say, over 75 years of age -- might be assigned a score of 1, and receive a reduced dose for patients with that score. A patient who is both older and has certain co-existing medical conditions (such as heart problems) might be assigned a score of 2, and receive an even lower dose schedule assigned to that score.
Such an approach would systematize the dosing of the patients within trials.
Another creative approach that was discussed came up in the presentation by Dr. Maria-Victoria Meteos of the University of Salamanca, Spain. She described a trial that is testing an initial therapy that consists of two combination regimens: Melphalan, prednisone, and Velcade ("MPV"); and Revlimid and low-dose dexamethasone ("Rd"). However, the trial not only combines these regimens, but compares two different ways of combining them.
One set of patients will receive the two regimens in sequence - a set number of cycles of MPV therapy first, followed by another set number of cycles of Rd.
Another set of patients, in contrast, will receive the regimens in a staggered way. Each patient first will receive a cycle of MPV; then a cycle of Rd; then another cycle of MPV; and so on.
Meteos and her colleagues believe the staggered approach could yield better results. But they are not certain, so they decided to test it within the trial they designed.
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Boris Simkovich - Name: Boris Simkovich
Founder
The Myeloma Beacon
Re: IMW 2011 Multiple Myeloma Discussion - Day 3
Unfortunately, we don't have time right now to post the rest of the information about Thursday's sessions because we have to head off to the Friday sessions. We'll post more about both day's sessions, however, later on Friday and/or over the weekend.
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Boris Simkovich - Name: Boris Simkovich
Founder
The Myeloma Beacon
11 posts
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