BY GARY PETERSEN
Some patients may not agree with this, but if nothing changes, nothing will change. The consensus opinion of myeloma specialists, which is confirmed by data from the NCI (National Cancer Institute), is that 85 to 90% of myeloma patients will not be cured and will one day become high risk and become non treatable. It is just a matter of time! In addition it takes 2 to 4 billion dollars to develop a new drug and the NCI (National Cancer Institute) has yearly research funding for myeloma of $45 million, so any myeloma drug development is dependent on drug company funding. Drug companies put their money where they will be most profitable, and as a result myeloma gets little attention and funding, and the efforts of drug companies go toward the common cancers, cancer of the breast, lung and prostate.
What do we do to focus on myeloma, an orphan cancer? I think the MMRF (Mutltiple Myeloma Research Foundation) has done a great job in focusing limited funds on some of the best potential drugs. However, sometimes the best possibilities for cure are not drugs but the patient's own immune system, and these excellent treatment options are not a pill which can excite a drug company for investment. This is what we found with the new MCRI (Myeloma Crowd Research Initiative).
The MCRI asked the world of myeloma researchers to enter their best ideas for a cure for high risk disease, and these were then ranked by some of the top myeloma specialists and researchers in the world. Doctors from the likes of MD Anderson, Mayo Clinic, Dana Farber, Memorial Sloan Kettering Cancer Center, to name a few of the best cancer research centers in the world. The top two proposals were immune therapy approaches, or those where a patient's own immune system is energized to fight the disease no matter if it is high or low risk. To say this is exciting is such an understatement, however to see the light of day these projects need your support. You can help yourself if you support one the following superior possibilities for a CURE. A recent press release by the MCRI can be viewed if you CLICK HERE.
CAR T Cells Targeting CS1 and BCMA by Dr. Hermann Einsele, MD and Dr. Michael Hudecek, MD of the University of Würzburg, Germany
CAR T Cells are an intensely exciting area of research, showing a more than 90% response rates when used with patients who have failed standard therapies in leukemia. According to Dr. Michael Sadelain of the Memorial Sloan Kettering Cancer Center and co-founder of Juno Therapeutics, “CAR T therapy is at the same time cell therapy, gene therapy, and immunotherapy. It represents a radical departure from all forms of medicine in existence until now."
The same exciting potential is now coming to multiple myeloma. Today, CAR T Cell therapy seems to be a hot topic, an overnight success, but it has been many years in the making. Doctors Einsele and Hudecek have been deeply involved in CAR T cell and immunotherapy work for many years. For their study, a patient’s T Cells are removed from a blood sample and are then engineered with a specific CAR T cell receptor. After a two week period to allow the cells to expand and grow, they are given back to the patient via injection. The engineered CAR T cell can now seek and destroy the myeloma cells. The selection of the right target is critical. The doctors want targets found only on myeloma cells and not on normal cells and have selected CS1 and BCMA. They note that CS1 is found on all myeloma cells, while BCMA has slightly lower occurrence, but chose to use two targets instead of one for greater impact. They have found that after treatment, a small percentage of patients have cells that are smart enough to hide the target marker, called “immune escape." By using two targets, they have a better chance of finding and killing all of the myeloma cells.
CAR T Cells can give unwanted side effects in a small number of patients because they are so powerful and take effect so quickly, sometimes creating a cytokine-release syndrome (CRS) when the myeloma cells die. If any patients exhibit severe side effects, they can administer an antibody as an emergency brake, which immediately stops the effect in patients.
For this study, the therapy is a single treatment and is not used with transplant or other combination therapies. It is now in pre-clinical work before it can be used in a Phase I clinical study. This study will be applicable for high-risk patients who have failed standard myeloma therapies but will also be appropriate for normal risk patients regardless of genetic features.
To learn more about this important project, read or listen to the Myeloma Crowd Radio Interview with Doctors Einsele and Hudecek.
Immunotherapy using MILs and autologous transplant by Dr. Ivan Borrello, MD, PhD of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Dr. Borello is working to create a patient-specific immunotherapy using enhanced T cells from the patient’s own bone marrow, for truly personalized medicine. He has found the marrow infiltrating lymphocytes (MILs) inside of the bone marrow to be more indicative of a patient’s disease rather than taking a blood sample. “Several years ago we did experiments where we took blood and bone marrow from patients and we activated these cells with beads in the laboratory. We showed that upon activation there was no increase in tumor specificity or tumor recognition of the cells that were derived from the blood. Whereas, in contrast, the bone marrow cells or the MILs from the patients had roughly a 100-fold increase in tumor specificity,” says Dr. Borrello.
The higher the specificity, the higher the chance a patient has of going into remission. After he extracts T cells from the bone marrow in an individual patient (similar to a bone marrow biopsy), he expands them a hundredfold outside of the body in the presence of the tumor cells, which help them recognize which targets to hit when given back. Three to four days after autologous transplant, he gives them back to the patient. When they are re-introduced, they target the hundreds of proteins that could be causing tumor growth for that patient, not just a single protein. This is an open clinical trial today for patients with high-risk genetic features. Compared to CAR T Cells, this approach targets hundreds of proteins versus one or two and limits the “immune escape” that can occur in the CAR T cell approach.
By targeting the specific disease-causing proteins in each patient, Dr. Borrello hopes “that the likelihood of such antigen escape variance are potentially significantly less.” The treatment is used in conjunction with autologous transplant to take advantage of the time where the transplant takes a patient’s lymphocyte count down to zero. The body automatically tries to repopulate these counts, giving the new, enhanced T cells a chance to expand twice– once in the lab and then again as part of the natural growth that occurs after stem cell transplant.
In the future, the treatment may be successful with high-dose chemo but not as high as transplant requires. The side effects of the treatment have been minimal, especially compared to the CAR T Cell potential effects. This third clinical study is now open for high-risk genetic feature patients who have not yet had stem cell transplant, but they can have had other prior therapies. The study uses lenalidomide as follow-up treatment because it has anti-myeloma properties as well as immune system boosting properties.
To learn more about this important project, read or listen to the Myeloma Crowd Radio Interview with Dr. Borrello.
To learn more about how to enroll in the clinical trial, click here.
Now it is your turn to help yourself. You can start a fund raising page or contribute to mine and I will split the funds equally between these two excellent proposals. My goal is to raise $20,000, and I commit to contribute $20 for every $1000 my team collects until we meet our goal, and if we meet our goal I will SKY DIVE FOR MYELOMA!
Good luck and God Bless your Myeloma Journey/ firstname.lastname@example.org
about the author
Gary is a myeloma survivor and patient advocate. His work centers around helping patients live longer by helping them to find facilities who are beating the average survival statistics. You can find Gary's site at www.myelomasurvival.com and follow him on Twitter at @grpetersen1