Immune Function Linked To Long-Term Survival In Multiple Myeloma
Results from a small Australian study provide new evidence that the immune systems of myeloma patients may play an important role in why some patients survive much longer than others.
In particular, the Australian researchers found that myeloma patients who live for more than 10 years after diagnosis have more robust immune function as compared to other myeloma patients.
Certain killer immune cells were more common, and divided more readily, in long-term myeloma survivors than in patients with shorter survival.
The investigators also found that long-term survivors had more helper cells (which promote immune responses) and fewer regulatory cells (which suppress immune responses) than other myeloma patients.
According to the researchers, understanding how the immune system behaves in long-term survivors may provide insights helpful for the development of immune-based myeloma therapies.
Dr. Leif Bergsagel from the Mayo Clinic, who was not involved with the study, agreed that the study results call for further research into therapies that affect a myeloma patient’s immune response.
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MORE INFORMATION News articles about: Forum discussions about: Also, see the Beacon's August 2013 update on multiple myeloma survival and the September 2013 update on multiple myeloma risk categories. |
He also said that the findings support the view that characteristics of a myeloma patient’s immune system play an important role in survival.
“As much as I believe that tumor genetics are of paramount importance, I also think the changes in the host immune system may contribute to progression from MGUS [a myeloma precursor disease] to multiple myeloma, and in long-term disease control,” said Dr. Bergsagel.
However, he also indicated that disease characteristics – such as lower tumor mass, responsiveness to therapy, chromosome abnormalities, and genetic mutations – that differ across patients may lead to different immune responses in patients who experience long-term survival.
Background
Previous evidence has shown that the immune system is impaired in patients with active multiple myeloma. Components of the immune system – including T cells, B cells, natural killer cells, and dendritic cells – are considerably altered.
Immunomodulatory drugs, such as thalidomide (Thalomid), Revlimid (lenalidomide), and Pomalyst (pomalidomide, Imnovid), boost the patient’s immune system to better enable it to attack and destroy myeloma cells.
T cells are a particular type of white blood cells that help the body to identify and kill various types of microbes and cancers.
Two distinct types of T cells, called killer (or CD8) cells and helper (or CD4) cells, work together to mount immune responses. As their names suggest, killer cells can directly kill infected or cancerous cells, while helper cells secrete proteins that aid in the development of killer cells.
Helper cells are further divided into a number of subsets based on the type of proteins they secrete. In the current study, the Australian researchers focused on a particular subset of helper cells called T helper 17 (or TH17) cells that secrete interleukin-17.
Regulatory T cells, on the other hand, are helper cells that suppress immune responses. Previous studies have yielded mixed results regarding the frequency and role of regulatory cells in myeloma patients.
Other studies have examined the immune systems of myeloma patients who show long-term disease control (see related Beacon news). Results from these studies indicate that patients with long-term disease control may have increased numbers of killer cells and fewer regulatory cells.
Long-term survival with multiple myeloma is oten defined as survival of 10 years or longer after diagnosis. Several factors such as younger age, lower tumor mass, and response to therapy have previously been associated with long-term survival.
The Australian researchers hypothesized that the immune function of multiple myeloma patients with long-term survival is different from that of patients with shorter survival.
In the current study, the Australian investigators sought to further characterize differences in immune function between long-term survivors and other myeloma patients.
Study Design
Twenty patients who were treated at the Royal Prince Alfred Hospital in Sydney, Australia, for more than 10 years after diagnosis were designated as long-term survivors and included in this study.
The median age of these patients at diagnosis was 58 years, with an age range of 32 years to 73 years.
All patients had received conventional chemotherapy, and 40 percent had been treated with novel agents, such as thalidomide, Revlimid, or Velcade (bortezomib). Half of the patients had undergone autologous (own) stem cell transplantation, and 15 percent had undergone allogeneic (donor) stem cell transplantation.
The researchers compared various characteristics of the immune systems of these 20 long-term survivors with data for 264 "short-term follow-up" myeloma patients. The latter group included 144 myeloma patients who had been visiting the clinic for shorter periods of time, as well as 120 patients who had participated in an Australian clinical trial that investigated the role of thalidomide maintenance therapy.
The 264 short-term follow-up patients, it should be noted, likely included some patients who will become long-term survivors, meaning that the comparisons in the study were not strictly between results for long-term myeloma and shorter-term myeloma survivors.
Also, the number of short-term follow-up patients included in the specific immune system comparisons carried out during the study varied due to data availability issues.
The researchers also compared the data from long-term myeloma survivors and short-term follow-up myeloma patients with data from a group of healthy individuals.
Study Results
The researchers first measured the frequency of various killer cell clones. A clone is a group of immune cells that are identical. Once an immune cell recognizes a specific target, such as a multiple myeloma cell, it multiplies rapidly to produce a large number of clonal cells. Such clonal expansion of killer cells is a sign of immune system activity against a target.
The researchers found killer cell clones in 100 percent of long-term survivors, but only in 54 percent of short-term follow-up patients who were treated at their institution and 48 percent of patients who participated in the clinical trial.
Based on these results, the researchers conclude that long-term survival may be linked to higher immune system activity against myeloma.
Next, the researchers examined the ability of clonal killer cells to multiply under laboratory conditions. They found that clonal killer cells from long-term survivors proliferated at a much higher rate than those of short-term follow-up patients. The median proliferation rate was about ten times higher for clonal cells from long-term survivors (62 percent versus 6 percent).
Since TH17 helper cells and regulatory cells oppose each other’s function, the researchers next sought to study the balance between these cell types in long-term survivors.
Comparing the frequencies of these two cell types, the researchers found that short-term follow-up patients had markedly fewer TH17 helper cells, but more regulatory cells, than long-term survivors or healthy individuals.
In fact, long-term survivors had a lower ratio of regulatory T cells to helper cells than healthy patients, suggesting that helper T cells are particularly important for long-term survival of myeloma patients.
Based on these results, the researchers conclude that the ratio of regulatory cells T cells to TH17 helper cells may be a key indicator for immune response in myeloma patients.
For further information, please see the study in Blood Cancer Journal.
Related Articles:
- Early Use Of Radiation Therapy Associated With Shorter Survival In Multiple Myeloma
- Sustained Complete Response To Initial Treatment Associated With Substantial Survival Benefit In Multiple Myeloma
- Importance Of Factors Affecting Multiple Myeloma Survival Changes With Patient Age
- Eyelid-Related Complications Of Velcade Therapy: New Insights And Recommendations
- Stem Cell Transplantation May Be Underutilized In Multiple Myeloma Patients In Their 80s
Thank you Sruti Krishna for this great review of an important small Australian study. I feel that this is only the tip of the iceberg in upcoming studies which will emphasize the robustness of our own immune response to MM as a key indicator of overall survival and QOL.
Now we need more research on specific natural therapies to enhance our immune response and tolerate chemotherapeutic treatment. For example, curcumin, thymus extract, astragalus, and several mushroom extracts all have evidence of beneficial effects. Acupuncture, energy work, meditation, and even prayer have demonstrated benefits.
But no pharmacological company will study these approaches. NIH in US has limited funding, but has sponsored interesting research in integrative care, as has German Komission E. Ultimately, we all need to follow the effect of these therapies on our individual disease, and labs which reflect our immunocompetence (CBC, immunoglobulins, and hs-cRP). Jan
My wife has dealt with her light chain myeloma now for 5 years. She had an auto stem cell transplant October 2008 in which she had a very good response. She has no damage caused by the myeloma other than kidney damage. No bone issues or no other organs have been affected. Her kidney function was roughly 20% when diagnosed and the doctors have been able to maintain that 20% function up until the last 8 to 10 months. She has been on sub-q velcade, dex and in the last 6 months, oral cytoxan. Her creatinine shows that her kidneys are wearing down, not from the protein, but because her 20% kidneys have been doing the work of 100% funtion kidneys. Her nephrologist has given her a time frame of 6 months to a year before she will require dialysis. She has a fistula in her arm in preparation for dialysis. Her myeloma specialist has talked about another stem cell transplant to get her into remission and then put her on the kidney transplant list so that she could get a new kidney. I have said I would be a live donor.
There are a lot of questions about this but one thing we know is that if she was able to have the kidney transplant, she would have to go on to a multitude of immune suppression drugs to prevent her body from rejecting the kidney. Knowing that the immune system is critical in helping to fight the myeloma, will the suppression drugs allow the myeloma to become active quicker? She has received IVIG since her transplant because of her weak immune system. How would all of this play out? Some doctors have said accept the fact about her kidneys, remain on maintenance treatment, and that dialysis would be better to deal with than doing the kidney transplant and dealing with the side effects of the immune suppression drugs and the possibility of the myeloma re-occuring quicker. Doctors do agree that with a new kidney, it would open up the capability of using some of the new drugs that she cannot use because of her kidney function. Has anyone had the similar situation and what was your treatment?
Dear Tommy. I am sorry to hear about your wife condition. May be kidney and bone morrow transplantation is a way to go. I don't think that it available outside of clinical studies.
Bellow the link to the study -"Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders (BMT)"
http://clinicaltrials.gov/show/NCT01758042
Dear Tommy, I'm sorry to hear your wife's story. From my perspective, the risk of a kidney transplant and immunosuppressive medications afterward with MM is too high, for the reasons you listed. I know a 61 year old practicing lawyer who has had dialysis every two to three days for 25 years, and is doing very well with it.
The clinical trial listed above by Igor is with allo stem cell transplants, a whole different situation. Dialysis would also enable the use of higher doses of medications that she cannot tolerate now. In any case, seeking out expert opinions in MM specialist centers is highly recommended; you will likely encouter several possibilities to ponder.
I also wanted to add to my first entry the importance of good nutritional (especially an anti inflammatory diet) and exercise (aerobic, flexibility and strengthening). Warm water immersion (hot tubs) and various gentle manipulative therapies are useful as well. Best wishes and thankful news to all! Jan
I would like to underline what Dr Jan Stafl has said. The story emphasizes the importance of our immune systems in managing our myeloma, and there are things that we survivors can do to nurture our immune systems: Exercise, nutrition, sleep, and stress management are all important.
Diagnosed and on my third year with MM My light chains where over 5,000. After three years of chemo they are down to 620 and reducing every 21 days after chemo and blood work done. I have had no transplant. I am 74 years of age. The Dr. said I had MM for about a year before I was diagnosed. As long as my light chains continue to reduce I will stay on the chemo I am on and go for another when this one stops working. Velcade carried me for 1 year with good response.I am now on pomalyst and dem. and have been for 5 months. I have good energy, good appetite gained weight. I was 88 pds on the on set and now ll9. I have joined a walking club 3x a week walking l mile each M W F. I am starting a strenghing excerise class on Fridays. It seems all of you have had transplants. I try to be strong because I have so much to be thank-ful for with my chemo and blood work except light chains. I lost my dearly beloved husband 5 years ago and 2 years later MM. We were married 49 years and looked forward to 50.I know my light chains do not compare with any of yours I am suspecting it's the transplant for you guys. I have wonderful children (4) living all around me. Grandchildren (8) and 2 great and 1 on the way. thanks for listening and please add anything you can if you can think of anything. Also my cbc are excellant! Dot
Hello everyone. My brother was diagnosed with multiple myeloma. In which he had to get surgery on his femur he has tumor on his arm he is currently stage 3. He was at Duke University in North Carolina we transferred him to Phila in which they placed him in a nursing home/rehab center. He is 57. They started his chemo treatment at Abramson Center. This is a big plung for him in which he is feeling like he is the only one going through this. However I honestly dont feel like a nursing home can give him the treatment that he needs. Just needing to vent.
Hi Donna,
Sorry to hear about your brother's situation. We can understand that he might feel a bit isolated in his new environment. There are a number of knowledgeable myeloma specialists at the Abramson Center, however, so he is in good hands.
There are several people from the Philadelphia area who post regularly in the Beacon's discussion forum. You may want to explain your brother's situation in more detail there, describing any questions that you may have.
Or, if he is able to do so, your brother could also post in the forum.
No registration is necessary to post in the forum or to read the numerous discussions there.
Good luck!