BALTIMORE, Md. (Ivanhoe Newswire) -- What if the cure for cancer could be found in the body’s own immune system, with a little help from modern science? Now a new clinical trial is giving patients hope.
For Marty Melley life is best spent on the go.
“I always said if this thing ever got me it would be while I was moving, not while I’m standing still,” Marty Melley, has myeloma, told Ivanhoe.
“This thing” is multiple myeloma, a cancer of the bone marrow. Once diagnosed, patients usually have three to five years, Marty found out after the birth of his first grandchild.
“I wanted to see him grow a little bit,” Melley said.
After a stem cell transplant, Marty went into remission, but the cancer came back. That’s when he enrolled in a new clinical trial.
“We’re actually taking the patient’s own immune cells, and we’re genetically modifying them,” Doctor Aaron Rapoport, MD, at the University of Maryland Greenebaum Cancer Center, in Baltimore, Md., told Ivanhoe.
That army of t-cells are then able to recognize and attack the cancer cells. The therapy is done together with a stem cell transplant that helps rebuild the body’s blood system.
“Patients tolerate the infusion very well,” Doctor Rapoport said.
Initial results show that more than 80 percent of patients either went into a complete or near-complete remission or were close to it. Now 11 years after what appeared to be his death sentence, Marty has two grandsons to share his wisdom with.
“When you want to do something, don’t wait until the golden years, cause sometimes your golden years, the gold is used to pay the doctor bills,” said Melley.
A final analysis of the study is expected to be completed by 2014. Participants are all in advanced stages of myeloma. There’s also a new trial in the works to see how using the genetically engineered t-cells alone will work without a stem cell transplant. Researchers are also hoping to start using this type of therapy in other types of cancer.
Aaron Rapoport, MD, Gary Jobson Professor in Medical Oncology at the University of Maryland School of Medicine and researcher at the University of Maryland Greenebaum Cancer Center, talks about a new clinical trial for myeloma.
Can you tell us about the trial you are working on?
Dr. Rapoport: Sure. Myeloma is one of the most common types of blood cancers and it affects about 20,000 new Americans per year and while there has been an enormous number of advances in the treatment of myeloma and the advent of a number of new drugs that are very active against it, it is still very hard to eradicate it and cure it; it almost always comes back. For many years, autologous stem cell transplants have been a very important part of the treatment of myeloma where we take stem cells from patients with myeloma and then we give the patients high doses of chemotherapy and then we give them their own stem cells back to rescue their blood counts and restore their bone marrow production. That has been quite effective and usually leads to complete responses in about 40% of patients and extended periods of disease free survivorship for a significant proportion of patients, but still the majority of patients who go through transplant, as well as who receive other forms of therapy for myeloma, do eventually have recurrence of disease.
What we have been working on for about the last 15 years is trying to learn how to harness the body’s own immune cells and try and get those to get into the fight against myeloma. We believe that the immune system plays a significant part in both the development of cancer as well as potentially the treatment for cancer. We know that when immune cells are depleted, such as in AIDS and other conditions like that, that cancers are much more common and so a robust and strong immune system helps to protect us from cancer. So by extension, we think that the treatment of myeloma and other blood cancers could be helped by developing ways to augment or enhance the immune system and to help the immune system to better recognize and attack the blood cancer cells including the myeloma cells. Through a series of trials over the last 15 years, we have tried to provide patients with a more robust immune system particularly after bone marrow transplant and we have tried to get those immune cells to better recognize and attack the cancer cells mainly the myeloma cells using initially vaccinations for proteins or markers that the myeloma cells may carry and most recently we have been trying to directly engineer the T cells, the immune cells so that they will be able to recognize and attack the myeloma cells. In our current trial, we are actually taking the patient’s own immune cells and we are genetically modifying them and genetically engineering them to express a new receptor on the surface of the cell and that receptor can potentially engage or attach to a myeloma cell that expresses the target or the marker that the receptor recognizes and those immune cells then could potentially kill those myeloma cells. For patients with myeloma who have certain characteristics namely their myeloma cells have a certain marker called LAGE-1 or NY-ESO-1, which is a marker that is expressed in probably about 50% of myeloma cases that these engineered T-cells could potentially recognize and attack the myeloma cells through that interaction.
So right now, it is the particular marker that about 50% of patients have, correct?
Dr. Rapoport: Well, about 50% of patients have that marker in the myeloma cells. And in addition for our particular trial, patients also have to have a particular tissue marker call A-2 and about 50% of the population has that. Probably altogether, maybe 1 in 4 patients with myeloma could be eligible for our trial. Ultimately, we would like to be able to do these kinds of therapies for all patients with myeloma and I think that new research that is under development now will hopefully allow that in the next several years, but this is sort of a proof of concept.
So given not including this trial, but given the current treatments, what is an average life expectancy then for someone that has multiple myeloma?
Dr. Rapoport: Well that has increased a great deal over the last decade as a result of the advent of new, these new medications. It varies depending on the characteristics of the myeloma. Some patients have more aggressive forms of myeloma; some have less aggressive forms of myeloma; currently, the average survival overall for myeloma is probably in excess of 4 years now, 4 to 5 years.
What have you found in preliminary results so far?
Dr. Rapoport: The initial responses that we have seen for patients on this trial of transplant, plus these immune modified T-cells, these genetically modified T cells has been very encouraging. We have seen nearly 80% of patients who have had very good partial responses, near complete responses, or complete responses, which are considered the best responses, after transplant for myeloma. Many of these patients are quite advanced in their disease. Many of them have already had prior transplants and this was essentially a second transplant for them being on the trial, so it is definitely a very advanced group of patients in terms of their myeloma. We have not seen any serious side effects from the T-cells. The patients tolerate the infusion very well. The T-cells do persist in the body for an extended period of time months up to a year and we have seen that they can go into the bone marrow and we have seen evidence that they can do some killing of the myeloma cells. So, we see evidence that they are working as we would hope they would, and I think the initial results have been very encouraging.
Is this something that would need to be repeated?
Dr. Rapoport: We do include in the trial an opportunity to do that if the patient has a recurrence of the myeloma while in the trial and the conditions are still appropriate to get the T-cells mainly that the myeloma cells expressed the marker and the T cells have gone away as typically they have when the myeloma; if and when the myeloma comes back. We do have the opportunity to give additional cells and we have actually done that in about two patients and we saw a very remarkable response in a patient that had very, very aggressive disease.
I know it is such an aggressive disease and it does take people away too early, but at the same time, for someone that has it, to be given that opportunity to have life just a little bit longer, can you talk about what you have seen that means to people and their families?
Dr. Rapoport: Well in this particular patient where I mentioned we gave another infusion of the T-cells when she was very weak and essentially on hospice with very advanced disease and she really came back to life for a couple of months. She was able to go out to restaurants and movies with her children and enjoyed a significantly improved quality of life, for a limited period unfortunately, but it gives us hope that for other patients like her in the future that some strategies like this can really have impact even in patients with very advanced disease. We have seen that in other gene-modified, engineered T-cells trials that are going on elsewhere, such as, at the University of Pennsylvania, our collaborating institution, which has been treating patients with advanced leukemia with genetically modified T-cells and there has been some wonderful stories of children who have had untreatable, very advanced leukemia who have gone into long remissions and been able to go back to their normal lives and go back to school after getting genetically-modified patient derived T-cells and so that is enormously gratifying to see that and really most not only a dream come true for the patients, but for the all of those who have been laboring in the field for many years trying to make this type of therapy that is using a patient’s own immune system to fight against their own cancer a reality.
What is that like for you to be able to be a part of this work?
Dr. Rapoport: It is a great privilege. I feel very fortunate to have been involved in this type of work for now, 15 years. I feel very privileged and fortunate to help develop those trials; to be able to offer these innovative therapies to patients and to begin to see some of the fruits of our labors.
Are there any thoughts about using this in a population that perhaps is not as advanced? Have you considered trying this in people that maybe are in those beginning stages that have not been overwhelmed by their own body yet?
Dr. Rapoport: I think that these patients who at this time don’t really have a curative therapy for their disease, we learn more about this form of therapy and have an even better handle on its efficacy. Its safety that we would hope to be able to offer these kinds of therapies to patients in the earlier stage of the disease and hopefully at a time when it would be more able to be eradicated; rather than waiting until they have relapsed multiple times or gotten to an advanced stage where the myeloma has become very difficult to treat by any means. If we can continue to show good safety and efficacy in the most challenging patients it makes sense to move it to the less challenging patients who potentially have even more to gain.
What does a partial response mean and then we can talk about the patient a little bit?
Dr. Rapoport: A partial response is when the myeloma markers go down significantly, but not all the way and if that partial response is sustained and lasts for an extended period of time then that is also good. These T-cells are really mainly going to be able to attack the myeloma cells that express the marker that they recognize. It is possible that if a patient’s myeloma is sort of a mixture of these markers positive cells and marker negative cells that the T-cells may go after the marker positive cells and leave the marker negative cells and that may be okay, because myeloma cells that express these LAGE-1 or NY-ESO-1 markers tend to be more aggressive. Those tend to be more resistant and more rapidly growing.
Would a partial response mean someone maybe that you lost, but whose life was extended during the trial?
Dr. Rapoport: No, partial response is talking about what happens to the myeloma markers. If the patient can live for an extended period of time with a partial response even though the myeloma is not cured, it could be that the aggressive component of the myeloma is knocked down or knocked out and they are left with kind of a more indolent or kind of slow growing part of it and in the patient that you will be interviewing, he actually had very advanced myeloma. He actually has had myeloma for, close to 10 years. He had a transplant on one of the earlier trials using T-cells plus a vaccine and he had a good period of remission and then he had a recurrence and then had another recurrence and kept sort of coming back and so that was why we put him on the new trial and with these gene-modified T-cells, and he has had a good partial response. He only has a small level of disease, but he has a great quality of life and he is now, I think a year and three months after these gene-modified T-cells and doing very well without any maintenance therapy, just doing well, enjoying his grandkids and making people laugh and he is working part-time, so.
Is there a certain population that gets hit by it more age wise or is it sort of across the board?
Dr. Rapoport: It definitely occurs more in older adults. The average age at diagnosis is 69. African-Americans are affected more frequently than Caucasians. I say it afflicts more than 20,000 new Americans every year.
What’s next for all of this?
Dr. Rapoport: For many years I have been working in the field of bone marrow stem cell transplantation for blood cancers and I have seen both the promise and the pitfalls of that form of therapy that has terrific successes in patients with very advanced leukemia, lymphoma, myeloma; all variety of blood cancers, but there are also side effects when you are transferring cells from another person into a patient and sometimes those side effects can be quite serious and life threatening and so, one of the long sought goals of cancer therapy has been to try and harness the power of the patient’s own immune system to fight against their cancer and as a result of better understanding of how the immune system works and how cancers evade the immune system and suppress the immune system as well as advances in technology for how to activate the immune system and engineer it to attack things that we want it to attack, I think we are beginning to really see the great promise of that form of cancer therapy in its enormously satisfying, humbling and really gives all of us in the field tremendous hope for the future and expectation of even greater success.
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