Investigational monoclonal antibodies, such as daratumumab and elotuzumab, could potentially change the role of stem cell transplantation for patients with multiple myeloma. These new therapies, and others on the horizon, offer options for patients who are ineligible for a stem cell transplant, and serve as a pretreatment method for patients who wish to delay the procedure.
To discover how these advances will impact patients, OncLive interviewed Ravi Vij, MD, associate professor, Division of Oncology, Section of Bone Marrow Transplantation, Washington University School of Medicine and the Siteman Cancer Center, on what the future holds for stem cell transplantation in multiple myeloma.
OncLive: What is the role of pretransplant therapy in myeloma?
Vij: The goal of the treatment is to establish some element of disease control prior to transplantation. We know that deeper levels of disease control usually correlate with longer survival. Therefore, the goal of therapy is to try and get the disease under control before a transplant will reduce it further, and provide more durable disease control.
How could pretransplant therapy change in the era of monoclonal antibodies?
It is a very vibrant area. It is difficult to say how things are going to evolve. We have a number of new drugs that are coming up—monoclonal antibodies or proteasome inhibitors—and these are going to be initially incorporated into the treatment of relapsed or refractory patients, but will gradually move their way to frontline treatment.
So far, we have generally used three drug combinations to produce the best responses, but it is possible in the future, especially with the monoclonal antibodies, that four drug combinations may be coming into vogue. Oral proteasome inhibitors will probably offer a more convenient regimen. I think its impact is more going to be on the durability of treatment for both transplant and non-transplant, the convenience of long-term oral administration.
What do you see as the role of transplantation in the future?
The role of stem-cell transplantation is still very secure in the treatment paradigm for patients with myeloma. The best results so far have been achieved with good induction therapy, early stem cell transplantation, and post-transplant maintenance. There are certainly patients who are not candidates or wish to delay transplantation, and for them to delay it until first progression is certainly an option.
As far as removing transplant from the paradigm, I think, in the immediate future, there will still be a need for transplantation for several years to come. As newer drugs are tested and trials are conducted and compared to stem cell transplantation, it is possible it will no longer be a necessary treatment paradigm one day. Right now it is something that I think helps the majority of the patients. It is a treatment that is relatively well tolerated, with usually a 1-2% treatment-related mortality rate. It is well tolerated even by older individuals.
Medicare pays for treatment for myeloma for those who are up to 78 years old. Although we may reduce the dosage a little bit in older individuals, they tolerate it well. Several studies have shown, at least in a retrospective manner, that older patients do benefit from stem cell transplantation.
What are some of the barriers to greater adoption of stem cell transplantation?
There is certainly a lot of work being done, which is looking at some of the barriers to greater adoption of stem cell transplantation. Socioeconomic status has been shown by our group to really matter. We know that certain demographics within the population are not even offered the opportunity to see a transplant physician, even if one is available in the vicinity. The number of transplants could literally double if appropriate referrals are made.
Often, the reluctance on the patient’s part can be overcome by explaining to them what the procedure involves, how well it is tolerated, and the benefits it has. It is often more difficult to convince a community physician to make the referral so one can at least have the opportunity to assess a patient. It is a procedure that, contrary to popular belief, is relatively well tolerated and still benefits a lot of patients.
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Showing posts with label monoclonal antibody. Show all posts
Showing posts with label monoclonal antibody. Show all posts
Thursday, March 12, 2015
Wednesday, January 22, 2014
Recent Advances in Multiple Myeloma Drugs
Pomalidomide (Pomalyst) rode impressive trial results to accelerated FDA approval last year, and Kenneth Anderson thinks it will prove a valuable new tool in the fight against multiple myeloma.
Better still, Anderson sees equally promising compounds at various stages of development and equally promising treatment trends that range from the transition to oral treatment regimes to the evaluation of early intervention efforts.
“The last two big drugs to be approved, pomalidomide and carfilzomib [Kyprolis], are second-generation compounds that work along similar principles as earlier medications in these classes, but to much greater effect,” Anderson said. “Looking down the road, however, the most promising names mostly belong to new monoclonal antibodies that haven’t been used against multiple myeloma before.”
Among the most exciting of the experimental compounds is elotuzumab, a monoclonal antibody currently in phase III trials for advanced disease in previously treated patients. In earlier trials, elotuzumab combined with lenalidomide (Revlimid) and dexamethasone (Decadron) has produced responses in up to 92% of such patients. Progression-free survival times have approached 3 years.
“Those numbers are really quite remarkable,” said Anderson, who hopes the drug replicates those figures in the last trial phase and wins approval in the next year or two.
Looking further down the development pipeline, Anderson noted that the FDA has awarded breakthrough status to daratumumab based on phase I trial results. The IgG1k monoclonal antibody, which targets the CD38 surface protein on myeloma cells, produced significant benefit in 47% of patients, most of them with advanced double-refractory disease. Progression-free survival exceeded 8 months for some patients, even though treatment stopped after eight cycles.
Moving from individual medications to trends, Anderson sees great potential in trials that combine classes of medications in new and potentially more effective ways. For example, researchers are pairing HDAC inhibitors with proteasome inhibitors, and also with immunomodulatory drugs. The potential exists, down the road, for a four or five-tier treatment that adds a monoclonal antibody to the mix in such a way that the benefit of each drug is additive or synergistic—hopefully enough to achieve cure.
So many medications could not have been used together a couple of decades ago, Anderson noted, because the side effects of each existing treatment was severe. Today’s medications, however, are not only more effective but also well tolerated, so we can contemplate using them in novel ways.
Another potentially transformative example of this, according to Anderson, is using the treatments to nip the disease in the bud by treating smoldering myeloma rather than waiting to see which cases progress.
“We don’t know that we can prevent development of active multiple myeloma,” Anderson said, “but our tools for both diagnosis and treatment have improved to the point that early treatment to prevent active disease can now be studied.”
Kenneth C. Anderson, MD, is program director and chief of the Division of Hematologic Neoplasias at the Dana-Farber Cancer Institute, and Kraft Family Professor of Medicine at Harvard Medical School in Boston, Massachusetts. -
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Better still, Anderson sees equally promising compounds at various stages of development and equally promising treatment trends that range from the transition to oral treatment regimes to the evaluation of early intervention efforts.
“The last two big drugs to be approved, pomalidomide and carfilzomib [Kyprolis], are second-generation compounds that work along similar principles as earlier medications in these classes, but to much greater effect,” Anderson said. “Looking down the road, however, the most promising names mostly belong to new monoclonal antibodies that haven’t been used against multiple myeloma before.”
Among the most exciting of the experimental compounds is elotuzumab, a monoclonal antibody currently in phase III trials for advanced disease in previously treated patients. In earlier trials, elotuzumab combined with lenalidomide (Revlimid) and dexamethasone (Decadron) has produced responses in up to 92% of such patients. Progression-free survival times have approached 3 years.
“Those numbers are really quite remarkable,” said Anderson, who hopes the drug replicates those figures in the last trial phase and wins approval in the next year or two.
Looking further down the development pipeline, Anderson noted that the FDA has awarded breakthrough status to daratumumab based on phase I trial results. The IgG1k monoclonal antibody, which targets the CD38 surface protein on myeloma cells, produced significant benefit in 47% of patients, most of them with advanced double-refractory disease. Progression-free survival exceeded 8 months for some patients, even though treatment stopped after eight cycles.
Moving from individual medications to trends, Anderson sees great potential in trials that combine classes of medications in new and potentially more effective ways. For example, researchers are pairing HDAC inhibitors with proteasome inhibitors, and also with immunomodulatory drugs. The potential exists, down the road, for a four or five-tier treatment that adds a monoclonal antibody to the mix in such a way that the benefit of each drug is additive or synergistic—hopefully enough to achieve cure.
So many medications could not have been used together a couple of decades ago, Anderson noted, because the side effects of each existing treatment was severe. Today’s medications, however, are not only more effective but also well tolerated, so we can contemplate using them in novel ways.
Another potentially transformative example of this, according to Anderson, is using the treatments to nip the disease in the bud by treating smoldering myeloma rather than waiting to see which cases progress.
“We don’t know that we can prevent development of active multiple myeloma,” Anderson said, “but our tools for both diagnosis and treatment have improved to the point that early treatment to prevent active disease can now be studied.”
Kenneth C. Anderson, MD, is program director and chief of the Division of Hematologic Neoplasias at the Dana-Farber Cancer Institute, and Kraft Family Professor of Medicine at Harvard Medical School in Boston, Massachusetts. -
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