There's been a lot of interest here about work being done on a potential vaccine-based approach to treating myeloma. So I thought people might be interested in some of the details of the vaccine pilot study that is going to be discussed at the upcoming ASCO meeting.
This is a link to the abstract for the study:
http://abstract.asco.org/AbstView_114_96605.html
Note that it is only a pilot study, and, according to the abstract, only one patient has started receiving the vaccine thus far.
I found a press release that has more information about the vaccine and the pilot study. Here it is:
In a poster session at ASCO highlighting research works in progress, Hearn Jay Cho, MD, PhD, Assistant Professor of Hematology and Medical Oncology at Mount Sinai, and his team will describe a new multicenter study investigating a vaccine targeting multiple myeloma, a currently incurable blood cancer. Dr. Cho’s team discovered that a gene called Melanoma Antigen Gene (MAGE)-A3 is highly expressed in multiple myeloma, and when that gene is “turned off,” the cancer cells die and the disease cannot proliferate. Dr. Cho and his team are investigating a vaccine based on the protein produced by the MAGE-A3 gene that triggers an immune system response intended to kill multiple myeloma cells.
Paired with an adjuvant, or a chemical that boosts immune response, and white blood cells primed with the vaccine, the MAGE-A3 vaccine is administered to patients undergoing autologous stem cell transplant. The first dose is delivered six weeks before stem cell transplant; the primed white blood cells are infused three days after the stem cell transplant and boosted by a second vaccination ten days after the transplant. Over the next 270 days, the patient receives six additional booster vaccinations.
The study plans to enroll 16 patients. If a 50 percent response to the vaccination is achieved, the research team will initiate a study in a larger patient population to further evaluate clinical efficacy.
“While currently available treatments for multiple myeloma help patients live longer and with a better quality of life, this disease remains incurable,” said Dr. Cho. “Immunotherapies have enormous potential in this patient population, and we hope the MAGE-A3 protein vaccine will bring us closer to a cure.”
[end of press release]
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Re: ASCO 2012 Details of vaccine pilot study
It is interesting that this is being done ONLY in the context of a transplant. This may provide just the edge necessary to ensure a long-term remission.
That said, why not try it with a relapsed patient without a requirement for transplant. Or in an approved front-line setting?
That said, why not try it with a relapsed patient without a requirement for transplant. Or in an approved front-line setting?
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Shane W
Re: ASCO 2012 Details of vaccine pilot study
Hi Shane,
Those are good questions that I really can't answer given my knowledge about these things.
However, I can clarify a few things.
First, just to make sure it's clear, the patients in this study are undergoing an autologous stem cell transplant after they have received induction therapy. It says in the poster abstract that, to be admitted into the study, patients have to have achieved at least a very good partial response to their induction therapy.
Second, it looks like they are combining this therapy with stem cell transplantation at least partly because the vaccine is administered as "vaccine-primed peripheral blood lymphocytes", meaning they add the vaccine to the patient's own lymphocytes drawn during the stem cell collection process.
I'll also speculate that testing the vaccine with newly diagnosed patients may give a better sense of whether the vaccine is really having an impact or not. By the time you get patients who have had several previous treatments, there is such variability among the patients that it may be hard to get a sense from the results whether the vaccine is really making a difference.
It wouldn't be difficult to draw conclusions with these patients, of course, if the results are really stunning. I guess, though, that the researchers are being conservative and organizing the trial so that results can be interpreted whether or not the vaccine is a huge success.
Those are good questions that I really can't answer given my knowledge about these things.
However, I can clarify a few things.
First, just to make sure it's clear, the patients in this study are undergoing an autologous stem cell transplant after they have received induction therapy. It says in the poster abstract that, to be admitted into the study, patients have to have achieved at least a very good partial response to their induction therapy.
Second, it looks like they are combining this therapy with stem cell transplantation at least partly because the vaccine is administered as "vaccine-primed peripheral blood lymphocytes", meaning they add the vaccine to the patient's own lymphocytes drawn during the stem cell collection process.
I'll also speculate that testing the vaccine with newly diagnosed patients may give a better sense of whether the vaccine is really having an impact or not. By the time you get patients who have had several previous treatments, there is such variability among the patients that it may be hard to get a sense from the results whether the vaccine is really making a difference.
It wouldn't be difficult to draw conclusions with these patients, of course, if the results are really stunning. I guess, though, that the researchers are being conservative and organizing the trial so that results can be interpreted whether or not the vaccine is a huge success.
Re: ASCO 2012 Details of vaccine pilot study
Hi Ricardo,
I am wondering the same as Shane.
High dose chemotherapy (HTC) should not be essential given that it is the stem cells that are primed following apheresis. Especially if patient has CR by molecular response.
Priming the stem cells is independent of high dose chemotherapy and it would be nice to see a trial design that does just that.
Do the leukopheresis.. prime those cells following collection and then re-introduce to patient without high dose chemotherapy, that option would tell the true potential of the vaccine.
I see the HTC as trying to cover bets...IOW's if vaccine does not work, patient has still received the 'standard of care'.
It would be nice to have a randomized trial, where those wanting the HDT are in one arm and receive their primed stem cells vs those who decline HDT and go straight to re-infusion with primed stem cells.
After all 50% of HDT with SCT already fail...so where's the risk in not subjecting patient to HDT and/or in other words the primed stem cells could take the place of HDT.
I am wondering the same as Shane.
High dose chemotherapy (HTC) should not be essential given that it is the stem cells that are primed following apheresis. Especially if patient has CR by molecular response.
Priming the stem cells is independent of high dose chemotherapy and it would be nice to see a trial design that does just that.
Do the leukopheresis.. prime those cells following collection and then re-introduce to patient without high dose chemotherapy, that option would tell the true potential of the vaccine.
I see the HTC as trying to cover bets...IOW's if vaccine does not work, patient has still received the 'standard of care'.
It would be nice to have a randomized trial, where those wanting the HDT are in one arm and receive their primed stem cells vs those who decline HDT and go straight to re-infusion with primed stem cells.
After all 50% of HDT with SCT already fail...so where's the risk in not subjecting patient to HDT and/or in other words the primed stem cells could take the place of HDT.
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: ASCO 2012 Details of vaccine pilot study
Ricardo, Shane, Suzierose,
Dr. Cohen is listed on the study. Since he is nice enough to comment here in the Beacon Forum maybe he will see this thread and give us a better idea of the thought process of the study. Just as a guess, it seems that the study is trying to as closely mimic an Allo transplant as possible. Under ideal circumstances, an Allo would be performed by doing Induction until a CR and than using high dose Chemo followed up directly with the immunotherapy of the Donor T Cells. If a patient did not get a Molecular Response after the Allo, additional immunotherapy from DLI's is usually tried. From every study I have seen, it is still the minority (in the 40-45% range) that achive CR with Induction alone. Since a study has to follow specific guidelines, maybe thinking is the Auto is more likely to get a lower tumor burden, therefore it is written into the study. Immunotherapy with Donor T Cells works best with a patient with a low tumor burden. Allos also work better in first CR than any other time.
Mark
Dr. Cohen is listed on the study. Since he is nice enough to comment here in the Beacon Forum maybe he will see this thread and give us a better idea of the thought process of the study. Just as a guess, it seems that the study is trying to as closely mimic an Allo transplant as possible. Under ideal circumstances, an Allo would be performed by doing Induction until a CR and than using high dose Chemo followed up directly with the immunotherapy of the Donor T Cells. If a patient did not get a Molecular Response after the Allo, additional immunotherapy from DLI's is usually tried. From every study I have seen, it is still the minority (in the 40-45% range) that achive CR with Induction alone. Since a study has to follow specific guidelines, maybe thinking is the Auto is more likely to get a lower tumor burden, therefore it is written into the study. Immunotherapy with Donor T Cells works best with a patient with a low tumor burden. Allos also work better in first CR than any other time.
Mark
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Mark
Re: ASCO 2012 Details of vaccine pilot study
That does make sense and is in line with my conjecture that this might provide the edge needed to ensure long-lasting remission with an ASCT. Some allos DO cure -- and if this serve as a proxy, it would be great.
At the risk of being overoptimistic (while being frustrated at the same time), it seems that if we can get some patients into remission for ten years or longer, we cannot be THAT far from a functional cure.
And at least IMHO, messing with the same-old drug classes alone will NEVER do it. There has to be some innovative twist, such as using immunotherapy. Let's get our bodies working for us -- and not against us.
At the risk of being overoptimistic (while being frustrated at the same time), it seems that if we can get some patients into remission for ten years or longer, we cannot be THAT far from a functional cure.
And at least IMHO, messing with the same-old drug classes alone will NEVER do it. There has to be some innovative twist, such as using immunotherapy. Let's get our bodies working for us -- and not against us.
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Shane W
Re: ASCO 2012 Details of vaccine pilot study
Thanks to all for your interest and comments on this study. I'd be happy to explain the rationale for the trial and clarify a few points.
1) The vaccine targets a protein called MAGE-A3, which is expressed by several cancers but not by normal cells in the adult body, making it a good target for immune attack. About 40% of myeloma patients will express MAGE-A3 in their myeloma cells at diagnosis, and expression seems to increase when myeloma relapses.
2) The vaccine is given intramuscularly, like a flu shot. It's actually now in phase III trials in lung cancer and melanoma, with over 1600 patients treated to date. However it's never been given to myeloma patients or to those undergoing a stem cell transplant, so we needed to do this pilot study to show that it's safe and capable of generating an immune response in this specific population.
3) Mark - you are correct that we designed the trial to attempt to gain the benefit of an allo transplant (namely, an immune attack against myeloma) without the biggest harm (namely, graft-versus-host-disease). Thus after the first vaccination we collect and freeze a large number of patients' peripheral blood lymphocytes (white blood cells), some of which hopefully have been primed by the vaccine and are now poised to attack. Patients then undergo a typical stem cell collection followed by a standard stem cell transplant with high-dose melphalan. A few days after the stem cell infusion, we re-infuse the "primed" white blood cells (again, mimicking an allogeneic DLI but without risk of GVHD since it's their own cells), followed by multiple booster vaccinations designed to further activate and expand the cells.
4) In addition to detailed safety monitoring, we're doing extensive testing to assess pateints' immunity to MAGE-A3 and other myeloma proteins, and of course following their clinical responses as well. If this approach is safe and appears promising in this pilot study, we certainly plan to pursue larger studies powered to more formally assess efficacy.
Additional details can be found at clinicaltrials.gov (http://clinicaltrials.gov/ct2/show/NCT01380145).
1) The vaccine targets a protein called MAGE-A3, which is expressed by several cancers but not by normal cells in the adult body, making it a good target for immune attack. About 40% of myeloma patients will express MAGE-A3 in their myeloma cells at diagnosis, and expression seems to increase when myeloma relapses.
2) The vaccine is given intramuscularly, like a flu shot. It's actually now in phase III trials in lung cancer and melanoma, with over 1600 patients treated to date. However it's never been given to myeloma patients or to those undergoing a stem cell transplant, so we needed to do this pilot study to show that it's safe and capable of generating an immune response in this specific population.
3) Mark - you are correct that we designed the trial to attempt to gain the benefit of an allo transplant (namely, an immune attack against myeloma) without the biggest harm (namely, graft-versus-host-disease). Thus after the first vaccination we collect and freeze a large number of patients' peripheral blood lymphocytes (white blood cells), some of which hopefully have been primed by the vaccine and are now poised to attack. Patients then undergo a typical stem cell collection followed by a standard stem cell transplant with high-dose melphalan. A few days after the stem cell infusion, we re-infuse the "primed" white blood cells (again, mimicking an allogeneic DLI but without risk of GVHD since it's their own cells), followed by multiple booster vaccinations designed to further activate and expand the cells.
4) In addition to detailed safety monitoring, we're doing extensive testing to assess pateints' immunity to MAGE-A3 and other myeloma proteins, and of course following their clinical responses as well. If this approach is safe and appears promising in this pilot study, we certainly plan to pursue larger studies powered to more formally assess efficacy.
Additional details can be found at clinicaltrials.gov (http://clinicaltrials.gov/ct2/show/NCT01380145).
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Dr. Adam Cohen - Name: Adam D. Cohen, M.D.
Beacon Medical Advisor
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