This forum thread will be used by the Beacon Staff to post updates about the proceedings of the American Society of Hematology (ASH) meeting taking place on Day 3 (Monday, December 12) of the conference.
Beacon forum participants are free, however, to use this thread to comment on the updates, post their own updates or thoughts, and ask questions. Everyone is encouraged to participate.
Feel free to also check out the threads dedicated to Day 1, Day 2, and Day 4 of the ASH 2011 meeting.
For an earlier discussion of ASH 2011 presentation and poster abstracts, please see this thread:
https://myelomabeacon.org/forum/ash-2011-annual-meeting-multiple-myeloma-t692.html
Forums
Re: ASH 2011 Multiple Myeloma Discussion - Day 3
Today , the third day of ASH 2011, is THE day for myeloma material at the meeting. There are multiple sets of oral presentations, sometimes even overlapping, as well as a number of poster summaries of new research.
We'll be posting updates here in this thread of the forum throughout the day today as the oral presentations take place.
The first, early morning session of oral presentations is dedicated to trial results for potential new myeloma drugs. Some of the trials are for new drugs tested by themselves (that is, as "single agents"). Other trials are for new drugs in combination with existing myeloma therapies.
All the trials summarized below are for patients who have failed previous therapies for their myeloma.
In reviewing the results for the trials, it is important to pay particular attention to exactly how many previous therapies the patients have failed. This also can be captured by how long it has been since the patients, on average, were first diagnosed.
This is an important aspect of a trial patient's population because patient's who have received -- and eventually failed -- many previous treatment regimens are typically harder to treat. So response rates for even the best myeloma treatments will not be very high in such patients.
We'll be posting updates here in this thread of the forum throughout the day today as the oral presentations take place.
The first, early morning session of oral presentations is dedicated to trial results for potential new myeloma drugs. Some of the trials are for new drugs tested by themselves (that is, as "single agents"). Other trials are for new drugs in combination with existing myeloma therapies.
All the trials summarized below are for patients who have failed previous therapies for their myeloma.
In reviewing the results for the trials, it is important to pay particular attention to exactly how many previous therapies the patients have failed. This also can be captured by how long it has been since the patients, on average, were first diagnosed.
This is an important aspect of a trial patient's population because patient's who have received -- and eventually failed -- many previous treatment regimens are typically harder to treat. So response rates for even the best myeloma treatments will not be very high in such patients.
Re: ASH 2011 Multiple Myeloma Discussion - Day 3
Dr. Paul Richardson from the Dana-Farber Cancer Institute in Boston gave the first two oral presentations at the myeloma session early this morning at ASH.
The first of his presentations was about a Phase 1 study of MLN9708 in patients with previously treated myeloma.
MLN9708 belongs to the same class of drugs as Velcade (bortezomib), however, MLN9708 can be taken orally.
The goal of the study Dr. Richardson reviewed was to identify the best dosing for MLN9708. The study included 62 patients with a median of four prior therapies. Almost all had prior Velcade therapy, about three quarters had been treated before with Revlimid, and about half had prior thalidomide therapy. The median patient age was 65.
So far, about 60 percent of patients have discontinued the therapy, mainly due to progression of disease. The most common side effects were fatigue, low platelet counts, and gastrointestinal issues such as nausea, diarrhea, and vomiting. Only 8 percent of the trial participants experience peripheral neuropathy (PN), and no cases of PN were classified as serious (Grade 3 or higher). Dr. Richardson summarized the side effect and safety data for the drug by saying that the drug has an "excellent tolerability profile."
So far, data are available for 46 patients in terms of their response to the drug. 6 patients have had a partial response or better, for an overall response rate of 13 percent. 1 patient had a complete response. 1 patient had a minimal response, and 28 patients had stable disease.
Overall, Dr. Richardson said that the treatment showed good activity in heavily pre-treated patients, and that the drug will continue to be developed, with trials planned looking at combinations of the drug with other drugs, as well as trials in diseases other than myeloma.
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper37860.html
MLN9708-related news articles here at The Beacon: https://myelomabeacon.org/tag/mln9708/
The first of his presentations was about a Phase 1 study of MLN9708 in patients with previously treated myeloma.
MLN9708 belongs to the same class of drugs as Velcade (bortezomib), however, MLN9708 can be taken orally.
The goal of the study Dr. Richardson reviewed was to identify the best dosing for MLN9708. The study included 62 patients with a median of four prior therapies. Almost all had prior Velcade therapy, about three quarters had been treated before with Revlimid, and about half had prior thalidomide therapy. The median patient age was 65.
So far, about 60 percent of patients have discontinued the therapy, mainly due to progression of disease. The most common side effects were fatigue, low platelet counts, and gastrointestinal issues such as nausea, diarrhea, and vomiting. Only 8 percent of the trial participants experience peripheral neuropathy (PN), and no cases of PN were classified as serious (Grade 3 or higher). Dr. Richardson summarized the side effect and safety data for the drug by saying that the drug has an "excellent tolerability profile."
So far, data are available for 46 patients in terms of their response to the drug. 6 patients have had a partial response or better, for an overall response rate of 13 percent. 1 patient had a complete response. 1 patient had a minimal response, and 28 patients had stable disease.
Overall, Dr. Richardson said that the treatment showed good activity in heavily pre-treated patients, and that the drug will continue to be developed, with trials planned looking at combinations of the drug with other drugs, as well as trials in diseases other than myeloma.
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper37860.html
MLN9708-related news articles here at The Beacon: https://myelomabeacon.org/tag/mln9708/
Re: ASH 2011 Multiple Myeloma Discussion - Day 3
The next presentation, also by Dr. Richardson, was about another drug that also is in the same class of drugs as Velcade.
In particular, he presented combined data from U.S. and Australian Phase 1 studies of marizomib (NPI-0052),. At the time his presentation for today was prepared, 44 patients had participated in the U.S. study, and 25 patients had participated in the Australian trial.
The goal of both studies was to determine the best dose and dosing schedule for the drug.
The U.S. and Australian studies were not completely the same. Patients in the Australian trial were given marizomib plus dexamethasone from the start of the study. In the U.S. study, patients received dexamethasone if, after two cycles of treatment with marizomib alone, they were not achieving at least a minimal response.
Patients in the study had a median age of 62.5 and had received a median of six prior therapies.
During the testing of different doses for the drug, dose-limiting side effects occurred that included hallucinations, cognitive changes, and loss of balance. However, the side effects were reversible.
Other side effects included fatigue, nausea, vomiting, dizziness, headache, diarrhea, constipation, insomnia, weight loss, and shortness of breath.
No patients experienced low red or white blood cells, low platelet counts, or peripheral neuropathy.
The overall response rate (partial response or better) to the treatment was 19 percent. This would appear quite good, given how many previous therapies the patients in the studies had.
However, one needs to bear in mind that these were not single-agent studies. Most of the patients in the study eventually were treated with a combination of marizomib and dexamethasone, not just marizomib on its own.
Based on the results of the U.S. and Australian studies, Dr. Richardson stated that a 0.5 mg/m2 marizomib dose, twice weekly, should be studied further, alone or in combination with dexamethasone or Revlimid (lenalidomide).
He also suggested that marizomib might be useful for patients with different disease characteristics, such as patients with myeloma that has spread beyond the bone marrow.
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper37217.html
In particular, he presented combined data from U.S. and Australian Phase 1 studies of marizomib (NPI-0052),. At the time his presentation for today was prepared, 44 patients had participated in the U.S. study, and 25 patients had participated in the Australian trial.
The goal of both studies was to determine the best dose and dosing schedule for the drug.
The U.S. and Australian studies were not completely the same. Patients in the Australian trial were given marizomib plus dexamethasone from the start of the study. In the U.S. study, patients received dexamethasone if, after two cycles of treatment with marizomib alone, they were not achieving at least a minimal response.
Patients in the study had a median age of 62.5 and had received a median of six prior therapies.
During the testing of different doses for the drug, dose-limiting side effects occurred that included hallucinations, cognitive changes, and loss of balance. However, the side effects were reversible.
Other side effects included fatigue, nausea, vomiting, dizziness, headache, diarrhea, constipation, insomnia, weight loss, and shortness of breath.
No patients experienced low red or white blood cells, low platelet counts, or peripheral neuropathy.
The overall response rate (partial response or better) to the treatment was 19 percent. This would appear quite good, given how many previous therapies the patients in the studies had.
However, one needs to bear in mind that these were not single-agent studies. Most of the patients in the study eventually were treated with a combination of marizomib and dexamethasone, not just marizomib on its own.
Based on the results of the U.S. and Australian studies, Dr. Richardson stated that a 0.5 mg/m2 marizomib dose, twice weekly, should be studied further, alone or in combination with dexamethasone or Revlimid (lenalidomide).
He also suggested that marizomib might be useful for patients with different disease characteristics, such as patients with myeloma that has spread beyond the bone marrow.
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper37217.html
Re: ASH 2011 Multiple Myeloma Discussion - Day 3
Dr. Sagar Lonial from the Winship Cancer Institute at the Emory University School of Medicine in Atlanta gave the next presentation in today's early morning session of oral presentations..
He summarized results of a Phase 2 study of elotuzamab combined with Revlimid and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.
Elotuzamab is a drug under development by the pharmaceutical company Bristol-Myers Squibb. It is designed to identify proteins on the surface of myeloma cells and spur the patient's immune system to destroy the cancer cells. It was initially tested as a single agent, but did not show much efficacy when used that way, and further work indicated it might work particularly well in combination with Revlimid.
The study summarized by Dr. Lonial included 73 patients with a median age of 63 years old. Patients had to have at least 1, but no more than 3, previous lines of therapy. 55 percent had two or more prior therapies. None of the patients had previously been treated with Revlimid. The patients in the study had a median time since initial myeloma diagnosis of 4.5 years.
Patients were randomly assigned to receive either 10 mg/kg or 20 mg/kg elotuzumab by intravenous infusion on days 1, 8, 15, and 22 of a 28-day treatment cycle for the first two cycles and days 1 and 15 of later cycles.
Patients also received 25 mg Revlimid on days 1 through 21 of treatment cycles, and either 40 mg dexamethasone once weekly or 28 mg dexamethasone orally plus 8 mg dexamethasone by intravenous infusion on elotuzumab dosing days.
In addition, patients received a pre-treatment regimen of methylprednisolone (Medrol), or later in the study, dexamethasone; diphenhydramine (Benadryl) or an equivalent drug; ranitidine (Zantac) or an equivalent drug; and acetaminophen (Tylenol). These drugs were administered to reduce the incidence of infusion side effects that had been found to occur in earlier studies.
Results showed that the overall response rate was 82 percent across the two doses that were tested. The overall response rate was actually higher in the (10mg/m2) lower-dose regimen -- 92 percent. It was 73 percent in the (20mg/m2) higher-dose regimen.
12 percent of patients had a complete response and 32 percent had a very good partial response.
In the 10 mg/kg dose group, 100 percent of patients with one prior therapy responded to treatment and 85 percent of patients with two or more prior therapies responded to treatment.
The median time to response was 1.0 month. After a median follow-up time of 11.4 months, 22 percent of patients experienced disease progression in the 10 mg/kg dose group and 30 percent in the 20 mg/kg dose group.
The most common serious or severe side effects were low lymphocyte levels (lymphocytes are a type of white blood cell) in 16 percent of patients, low platelet levels (16 percent of patients), low white blood cell levels (15 percent of patients), and low red blood cell levels (11 percent of patients).
In addition, 63 percent of patients experienced infusion reactions, the most common of which were nausea (18 percent), headache (14 percent), fever (14 percent), and dizziness (12 percent).
The lower, 10mg/kg dose of elotuzumab is being tested further in combination with Revlimid and dexamethasone in two large, Phase 3 trials. One is in ewly diagnosed myeloma patients, the other is in relapsed/refractory patients.
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper36976.html
Elotuzumab-related news articles here at The Beacon: https://myelomabeacon.org/tag/elotuzumab/
He summarized results of a Phase 2 study of elotuzamab combined with Revlimid and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.
Elotuzamab is a drug under development by the pharmaceutical company Bristol-Myers Squibb. It is designed to identify proteins on the surface of myeloma cells and spur the patient's immune system to destroy the cancer cells. It was initially tested as a single agent, but did not show much efficacy when used that way, and further work indicated it might work particularly well in combination with Revlimid.
The study summarized by Dr. Lonial included 73 patients with a median age of 63 years old. Patients had to have at least 1, but no more than 3, previous lines of therapy. 55 percent had two or more prior therapies. None of the patients had previously been treated with Revlimid. The patients in the study had a median time since initial myeloma diagnosis of 4.5 years.
Patients were randomly assigned to receive either 10 mg/kg or 20 mg/kg elotuzumab by intravenous infusion on days 1, 8, 15, and 22 of a 28-day treatment cycle for the first two cycles and days 1 and 15 of later cycles.
Patients also received 25 mg Revlimid on days 1 through 21 of treatment cycles, and either 40 mg dexamethasone once weekly or 28 mg dexamethasone orally plus 8 mg dexamethasone by intravenous infusion on elotuzumab dosing days.
In addition, patients received a pre-treatment regimen of methylprednisolone (Medrol), or later in the study, dexamethasone; diphenhydramine (Benadryl) or an equivalent drug; ranitidine (Zantac) or an equivalent drug; and acetaminophen (Tylenol). These drugs were administered to reduce the incidence of infusion side effects that had been found to occur in earlier studies.
Results showed that the overall response rate was 82 percent across the two doses that were tested. The overall response rate was actually higher in the (10mg/m2) lower-dose regimen -- 92 percent. It was 73 percent in the (20mg/m2) higher-dose regimen.
12 percent of patients had a complete response and 32 percent had a very good partial response.
In the 10 mg/kg dose group, 100 percent of patients with one prior therapy responded to treatment and 85 percent of patients with two or more prior therapies responded to treatment.
The median time to response was 1.0 month. After a median follow-up time of 11.4 months, 22 percent of patients experienced disease progression in the 10 mg/kg dose group and 30 percent in the 20 mg/kg dose group.
The most common serious or severe side effects were low lymphocyte levels (lymphocytes are a type of white blood cell) in 16 percent of patients, low platelet levels (16 percent of patients), low white blood cell levels (15 percent of patients), and low red blood cell levels (11 percent of patients).
In addition, 63 percent of patients experienced infusion reactions, the most common of which were nausea (18 percent), headache (14 percent), fever (14 percent), and dizziness (12 percent).
The lower, 10mg/kg dose of elotuzumab is being tested further in combination with Revlimid and dexamethasone in two large, Phase 3 trials. One is in ewly diagnosed myeloma patients, the other is in relapsed/refractory patients.
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper36976.html
Elotuzumab-related news articles here at The Beacon: https://myelomabeacon.org/tag/elotuzumab/
Re: ASH 2011 Multiple Myeloma Discussion - Day 3
The presentation after Dr. Lonial's also discussed a combination treatment involving a new drug with Revlimid and dexamethasone.
In particular, Dr. Suzanne Lentzsch from the University of Pittsburgh School of Medicine presented results from a Phase 1/2 study of Treanda (bendamustine) in combination with Revlimid (lenalidomide) and dexamethasone (Decadron) in relapsed/refractory multiple myeloma patients.
Treanda is an alkylating agent, which is a class of drugs that includes myeloma treatments such as melphalan and cyclophosphamide (Cytoxan). It currently is approved by the U.S. Food and Drug Administration as a treatment for certain types of leukemia and lymphoma. It also is approve in some European countries as a treatment for myeloma.
The goal of the trial presented by Dr. Lentsch was to determine the maximum tolerated dose of the Treanda-Revlimid-dexamethasone combination, as well as its efficacy at the maximum tolerated dose.
Part of the motivation for testing this combination was the finding that the combination of melphalan, prednisone, and Revlimid ("MPR") has been an effective treatment in myeloma. Treanda, as was just mentioned, is in the same drug class as melphalan, and dexamethasone is a steroid like prednisone.
The study included 36 patients with a median age of 63 years old and a median of three prior therapies. All of the patients had previous been treated with either Revlimid or thalidomide. 79 percent of patients had previously received Revlimid, 48 percent had previously received thalidomide, and 34 percent had received both.
In addition, 69 percent of patients had received an autologous stem cell transplant.
25 patients (69 percent) received at least two treatment cycles and were assessed for treatment responses. Of these, 52 percent achieved a partial response or better. 24 percent achieved a very good partial response.
In addition, 24 percent of patients achieved a minor response and 16 percent had stable disease.
The estimated median progression free survival was 6.1 months. The estimated overall survival rate at 1 year after start of therapy is 93 percent. The median overall survival time has not yet been reached after.
Twenty-four percent of patients experienced severe low white blood cell counts during the course of the study, and 7 percent experienced severe low platelet levels. As a result, Dr. Lentzsch believes patients receiving this regimen in the future will also receive treatment with Neupogen or Neulasta to help prevent such side effects.
Otherwise, Dr. Lentzsch considers the three-drug regimen to be "safe and well-tolerated," and she also noted that the responses observed during the trial were fast and the regimen was effective even in patients who previously had been treated with Revlimid.
According to Dr. Lenztsch, the results indicate that the three-drug combination of Treanda, Revlimid, and dexamethasone is safe and well-tolerated in relapsed/refractory multiple myeloma patients up to 80 years of age. She also noted that response rates were fast and that the regimen was effective even in patients with prior Revlimid exposure. However, she suggested that due to the side effects, it should be used with Neupogen (filgastrim).
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper41680.html
In particular, Dr. Suzanne Lentzsch from the University of Pittsburgh School of Medicine presented results from a Phase 1/2 study of Treanda (bendamustine) in combination with Revlimid (lenalidomide) and dexamethasone (Decadron) in relapsed/refractory multiple myeloma patients.
Treanda is an alkylating agent, which is a class of drugs that includes myeloma treatments such as melphalan and cyclophosphamide (Cytoxan). It currently is approved by the U.S. Food and Drug Administration as a treatment for certain types of leukemia and lymphoma. It also is approve in some European countries as a treatment for myeloma.
The goal of the trial presented by Dr. Lentsch was to determine the maximum tolerated dose of the Treanda-Revlimid-dexamethasone combination, as well as its efficacy at the maximum tolerated dose.
Part of the motivation for testing this combination was the finding that the combination of melphalan, prednisone, and Revlimid ("MPR") has been an effective treatment in myeloma. Treanda, as was just mentioned, is in the same drug class as melphalan, and dexamethasone is a steroid like prednisone.
The study included 36 patients with a median age of 63 years old and a median of three prior therapies. All of the patients had previous been treated with either Revlimid or thalidomide. 79 percent of patients had previously received Revlimid, 48 percent had previously received thalidomide, and 34 percent had received both.
In addition, 69 percent of patients had received an autologous stem cell transplant.
25 patients (69 percent) received at least two treatment cycles and were assessed for treatment responses. Of these, 52 percent achieved a partial response or better. 24 percent achieved a very good partial response.
In addition, 24 percent of patients achieved a minor response and 16 percent had stable disease.
The estimated median progression free survival was 6.1 months. The estimated overall survival rate at 1 year after start of therapy is 93 percent. The median overall survival time has not yet been reached after.
Twenty-four percent of patients experienced severe low white blood cell counts during the course of the study, and 7 percent experienced severe low platelet levels. As a result, Dr. Lentzsch believes patients receiving this regimen in the future will also receive treatment with Neupogen or Neulasta to help prevent such side effects.
Otherwise, Dr. Lentzsch considers the three-drug regimen to be "safe and well-tolerated," and she also noted that the responses observed during the trial were fast and the regimen was effective even in patients who previously had been treated with Revlimid.
According to Dr. Lenztsch, the results indicate that the three-drug combination of Treanda, Revlimid, and dexamethasone is safe and well-tolerated in relapsed/refractory multiple myeloma patients up to 80 years of age. She also noted that response rates were fast and that the regimen was effective even in patients with prior Revlimid exposure. However, she suggested that due to the side effects, it should be used with Neupogen (filgastrim).
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper41680.html
Re: ASH 2011 Multiple Myeloma Discussion - Day 3
The final presentation that I'll cover from the early morning oral presentations was by Dr. Sundar Jagannath from Mount Sinai Medical Center in New York City.
He presented results from a Phase 1 study of BT-062 in patients with relapsed/refractory multiple myeloma.
BT-062 is a drug under development by the German company Biotest AG. It combines an antibody and a drug to kill the cancer cells. Antibodies help the body identify foreign objects that the immune system should defend against.
The goal of the BT-062 trial was to investigate the safety and efficacy of BT-062 and find its maximum tolerated dose.
The trial included 32 patients who had failed treatment with a drug in the same class as Revlimid and thalidomide, and also failed treatment with a drug in the same class as Velcade. Patients in the trial had a median of 7 previous anti-myeloma therapies, and were a median of six years from their initial diagnosis with myeloma when they entered this trial.
The median patient age was 62.
Of 28 patients whose response to treatment could be evaluated, 50 percent had stable disease or better.
However, no patients achieved either a complete response or very good partial response.
One patient achieved a partial response.
And two patients achieved a minor response.
One patient, who had a minor response, remained on treatment for over a year.
Side effects included mouth sores, hand-foot syndrome, blurred vision, and dry eyes, with the last two side effects primarily reported at very high doses. Most patients stopped the study due to disease progression, not side effects.
According to Dr. Jagannath, results from the study suggest that BT-062 is safe and shows evidence of clinical activity. Based on the results, a Phase 1/2 study has been initiated in multiple myeloma patients to further evaluate the safety and efficacy of BT-062. However, it will use a more frequent dosing schedule because other research has shown that the drug is eliminated from the body quicker than had been anticipated, meaning it has less time to be active against myeloma.
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper42689.html .
BT-062-related news articles here at The Beacon:
https://myelomabeacon.org/tag/bt-062/
He presented results from a Phase 1 study of BT-062 in patients with relapsed/refractory multiple myeloma.
BT-062 is a drug under development by the German company Biotest AG. It combines an antibody and a drug to kill the cancer cells. Antibodies help the body identify foreign objects that the immune system should defend against.
The goal of the BT-062 trial was to investigate the safety and efficacy of BT-062 and find its maximum tolerated dose.
The trial included 32 patients who had failed treatment with a drug in the same class as Revlimid and thalidomide, and also failed treatment with a drug in the same class as Velcade. Patients in the trial had a median of 7 previous anti-myeloma therapies, and were a median of six years from their initial diagnosis with myeloma when they entered this trial.
The median patient age was 62.
Of 28 patients whose response to treatment could be evaluated, 50 percent had stable disease or better.
However, no patients achieved either a complete response or very good partial response.
One patient achieved a partial response.
And two patients achieved a minor response.
One patient, who had a minor response, remained on treatment for over a year.
Side effects included mouth sores, hand-foot syndrome, blurred vision, and dry eyes, with the last two side effects primarily reported at very high doses. Most patients stopped the study due to disease progression, not side effects.
According to Dr. Jagannath, results from the study suggest that BT-062 is safe and shows evidence of clinical activity. Based on the results, a Phase 1/2 study has been initiated in multiple myeloma patients to further evaluate the safety and efficacy of BT-062. However, it will use a more frequent dosing schedule because other research has shown that the drug is eliminated from the body quicker than had been anticipated, meaning it has less time to be active against myeloma.
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper42689.html .
BT-062-related news articles here at The Beacon:
https://myelomabeacon.org/tag/bt-062/
Re: ASH 2011 Multiple Myeloma Discussion - Day 3
We're about to start the next morning session focused on myeloma here at ASH. It is more of a mixture of presentations than the first morning session. All of the presentations will review trial results. However, some of the trial results are solely for therapies that already are approved and available for general use. Other presentations involve "emerging" / potential new treatments for myeloma.
It's a very popular session -- there are no free seats, and the hall probably has a capacity of 600 or 700.
It's a very popular session -- there are no free seats, and the hall probably has a capacity of 600 or 700.
Re: ASH 2011 Multiple Myeloma Discussion - Day 3
The first presentation in the later morning session was by Dr. Antonio Palumbo of the University of Torino, Italy. He presented the final results of a long-running Phase 3 trial aimed at assessing whether Revlimid maintenance therapy is beneficial for newly diagnosed, older myeloma patients ineligible for a stem cell transplant.
All patients The trial Dr. Palumbo discussed had three groups of patients.
Two groups of the patients received induction therapy consisting of melphalan, prednisone, and Revlimid administered for nine cycles. Then half of the patients were placed on maintenance therapy with Revlimid (this group is usually designated "MPR-R"), while the other half of these patients received a placebo as "maintenance" therapy (this group is typically designated "MPR").
A third group received only melphalan and prednisone as induction therapy, then a placebo as "maintenance" therapy. This group is usually designated just "MP".
This trial was designed to answer the question: Is there a benefit to maintenance therapy with a novel agent -- specifically, the novel agent Revlimid.
At the same time, the trial also can shed light on the question: Is there a risk associated with Revlimid maintenance therapy in terms of secondary cancers?
The second question arose, actually, because this trial was one of three major trials that first revealed that Revlimid might be associated with an increased risk of secondary cancer.
The results of this trial are clear in terms of the impact of Revlimid maintenance on progression free survival. Revlimid maintenance has a clear, statistically significant positive impact on progression free survival.
Median progression free survival was 31 months for the MPR-R group of patients, 14 months for the MPR patients, and 13 months for the MP patients.
The picture is much, much less clear when attention turns to overall survival -- that is, how long patients are actually surviving when they are placed on these therapies.
The percentage of patients still alive at the four year mark in this trial was 59 percent for the MPR-R group, 58 percent for the MPR group, and 58 percent, as well, for the MP group.
In short, there is basically no difference.
There does seem to be a slight survival benefit developing in favor of the MPR-R group of patients. But it is just developing and it is unclear if it will be sustained.
Dr. Palumbo argued during his presentation that the progression free survival benefit for the MPR-R regimen was clear evidence in favor of Revlimid maintenance. Yet, for myeloma specialists who focus on overall survival, rather than progression free survival, as the key metric of a therapy's success or failure, his argument is not likely to be convincing.
Dr. Palumbo also shared the latest secondary cancer data from the trial. These day indicate that Revlimid maintenance as well as Revlimid induction therapy noticeably increases the rate of secondary cancers.
The statistics for one particular type of important secondary cancers ("non-invasive cancers") for each group were as follows:
MPR-R - 12 cases out of 150 patients
MPR - 10 cases out of 152 patients
MP - 4 cases out of 153 patients
Dr. Palumbo argued, however, that the increased risk of secondary cancer associated with Revlimid treatment is far outweighed by the benefit it conveys to myeloma patients. Most myeloma specialists agree with this perspective, and it is also the conclusion that the European Medicines Agency reached when it reviewed Revlimid's secondary cancer risk this past summer.
In both the introduction and the conclusion to his presentation, Dr. Palumbo said that evidence such as the results from the trial he reviewed today is moving myeloma in the direction of continuous therapy rather than specific periods of therapy as has typically been the case in the past.
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper37604.html
All patients The trial Dr. Palumbo discussed had three groups of patients.
Two groups of the patients received induction therapy consisting of melphalan, prednisone, and Revlimid administered for nine cycles. Then half of the patients were placed on maintenance therapy with Revlimid (this group is usually designated "MPR-R"), while the other half of these patients received a placebo as "maintenance" therapy (this group is typically designated "MPR").
A third group received only melphalan and prednisone as induction therapy, then a placebo as "maintenance" therapy. This group is usually designated just "MP".
This trial was designed to answer the question: Is there a benefit to maintenance therapy with a novel agent -- specifically, the novel agent Revlimid.
At the same time, the trial also can shed light on the question: Is there a risk associated with Revlimid maintenance therapy in terms of secondary cancers?
The second question arose, actually, because this trial was one of three major trials that first revealed that Revlimid might be associated with an increased risk of secondary cancer.
The results of this trial are clear in terms of the impact of Revlimid maintenance on progression free survival. Revlimid maintenance has a clear, statistically significant positive impact on progression free survival.
Median progression free survival was 31 months for the MPR-R group of patients, 14 months for the MPR patients, and 13 months for the MP patients.
The picture is much, much less clear when attention turns to overall survival -- that is, how long patients are actually surviving when they are placed on these therapies.
The percentage of patients still alive at the four year mark in this trial was 59 percent for the MPR-R group, 58 percent for the MPR group, and 58 percent, as well, for the MP group.
In short, there is basically no difference.
There does seem to be a slight survival benefit developing in favor of the MPR-R group of patients. But it is just developing and it is unclear if it will be sustained.
Dr. Palumbo argued during his presentation that the progression free survival benefit for the MPR-R regimen was clear evidence in favor of Revlimid maintenance. Yet, for myeloma specialists who focus on overall survival, rather than progression free survival, as the key metric of a therapy's success or failure, his argument is not likely to be convincing.
Dr. Palumbo also shared the latest secondary cancer data from the trial. These day indicate that Revlimid maintenance as well as Revlimid induction therapy noticeably increases the rate of secondary cancers.
The statistics for one particular type of important secondary cancers ("non-invasive cancers") for each group were as follows:
MPR-R - 12 cases out of 150 patients
MPR - 10 cases out of 152 patients
MP - 4 cases out of 153 patients
Dr. Palumbo argued, however, that the increased risk of secondary cancer associated with Revlimid treatment is far outweighed by the benefit it conveys to myeloma patients. Most myeloma specialists agree with this perspective, and it is also the conclusion that the European Medicines Agency reached when it reviewed Revlimid's secondary cancer risk this past summer.
In both the introduction and the conclusion to his presentation, Dr. Palumbo said that evidence such as the results from the trial he reviewed today is moving myeloma in the direction of continuous therapy rather than specific periods of therapy as has typically been the case in the past.
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper37604.html
Re: ASH 2011 Multiple Myeloma Discussion - Day 3
The next presentation was by Dr. Jesús San Miguel from the University Hospital in Salamanca, Spain.
He presented updated results from a Phase 3 clinical trial comparing the three-drug regimen Velcade (bortezomib), melphalan (Alkeran), and prednisone (VMP) to melphalan and prednisone alone (MP).
The goal was to determine if a previously reported overall survival benefit for the VMP regimen persisted after five years of follow-up. In addition, the researchers analyzed the risk of secondary malignancies in both treatment groups.
The analysis included 655 patients who were previously untreated and also ineligible for stem cell transplants.
Half the patients were randomly assigned to receive nine six-week cycles of VMP and the other half to receive MP alone.
After a median follow-up of 60.1 months, the median overall survival was 56.4 months for VMP patients versus 43.1 months for MP. In addition, the five-year overall survival rates of 46 percent and 34 percent for VMP and MP, respectively
.
The overall survival benefit of VMP versus MP was observed for several patient subgroups, including patients 75 years old or older (median survival of 50.7 months versus 32.9 months), patients with stage III multiple myeloma (median survival of 42.1 months versus 30.5 months), and patients with kidney disease (median survival of 56.8 months versus 36.7 months). However, no significant difference in overall survival was observed in patients with high-risk chromosomal abnormalities.
The researchers also discussed an analysis of the risk of secondary cancers associated with VMP therapy versus MP therapy. However, these data already were discussed in an update yesterday about a poster presentation summarizing the same data as well as other data related to Velcade and the risk of secondary cancers.
(Link: https://myelomabeacon.org/forum/ash-2011-multiple-myeloma-discussion-day-2-t759.html#p3268 )
Dr. San Miguel concluded that VMP resulted in a substantial long-term overall survival benefit compared to MP across a range of key patient subgroups, and that the risk of increased secondary cancers associated with the treatment is negligible or non-existent.
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper37551.html
He presented updated results from a Phase 3 clinical trial comparing the three-drug regimen Velcade (bortezomib), melphalan (Alkeran), and prednisone (VMP) to melphalan and prednisone alone (MP).
The goal was to determine if a previously reported overall survival benefit for the VMP regimen persisted after five years of follow-up. In addition, the researchers analyzed the risk of secondary malignancies in both treatment groups.
The analysis included 655 patients who were previously untreated and also ineligible for stem cell transplants.
Half the patients were randomly assigned to receive nine six-week cycles of VMP and the other half to receive MP alone.
After a median follow-up of 60.1 months, the median overall survival was 56.4 months for VMP patients versus 43.1 months for MP. In addition, the five-year overall survival rates of 46 percent and 34 percent for VMP and MP, respectively
.
The overall survival benefit of VMP versus MP was observed for several patient subgroups, including patients 75 years old or older (median survival of 50.7 months versus 32.9 months), patients with stage III multiple myeloma (median survival of 42.1 months versus 30.5 months), and patients with kidney disease (median survival of 56.8 months versus 36.7 months). However, no significant difference in overall survival was observed in patients with high-risk chromosomal abnormalities.
The researchers also discussed an analysis of the risk of secondary cancers associated with VMP therapy versus MP therapy. However, these data already were discussed in an update yesterday about a poster presentation summarizing the same data as well as other data related to Velcade and the risk of secondary cancers.
(Link: https://myelomabeacon.org/forum/ash-2011-multiple-myeloma-discussion-day-2-t759.html#p3268 )
Dr. San Miguel concluded that VMP resulted in a substantial long-term overall survival benefit compared to MP across a range of key patient subgroups, and that the risk of increased secondary cancers associated with the treatment is negligible or non-existent.
Abstract: http://ash.confex.com/ash/2011/webprogram/Paper37551.html
14 posts
• Page 1 of 2 • 1, 2