Beacon NewsFlashes – November 26, 2012
Researchers Observe High Rate Of Osteonecrosis Of The Jaw In Myeloma Patients After Stem Cell Transplantation – In a recent retrospective study, German researchers observed a high rate of osteonecrosis of the jaw (23 percent) in multiple myeloma patients who had a stem cell transplant prior to bisphosphonate therapy. Osteonecrosis of the jaw is a condition that is associated with a loss of blood supply to the jaw, causing the jawbone tissue to die. It can occur in multiple myeloma patients during bisphosphonate treatment. The researchers found that the risk for bisphosphonate-related osteonecrosis of the jaw was significantly higher for patients with rheumatism and recent dental work. In addition, the researchers found that higher rates of osteonecrosis of the jaw were associated with the duration of bisphosphonate therapy as well as the type and cumulative dose of bisphosphonate used. For more information, please see the study in the journal Onkologie (abstract).
Study Finds Late Relapses After Donor Transplantation In Myeloma – Results of a small, long-term follow-up study show that late relapses are possible in multiple myeloma patients after donor stem cell transplantation with reduced-intensity chemotherapy. At a median follow-up time of 9.8 years, the seven-year progression-free survival rate was 31 percent and the overall survival rate was 60 percent. Ten percent of patients relapsed within 6 to 12 years after the transplant, which the researchers described as surprising. The researchers found that being in remission at the time of the transplant and having chronic graft-versus-host disease, a common transplant-related complication, in which the donor cells recognize the patient cells as foreign and attack them, were associated with improved overall survival. For more information, please see the study in the British Journal of Haematology (abstract).
LLS Teleconference On Stem Cell Transplantation – On December 3, the Leukemia & Lymphoma Society (LLS) will sponsor a free teleconference call about stem cell transplantation for multiple myeloma and lymphoma. Dr. Edward Stadtmauer from the Abramson Cancer Center at the University of Pennsylvania and Dr. Jonathan Friedberg from the James P. Wilmot Cancer Center at the University of Rochester will lead the program, which begins at 1:00 p.m. Eastern Time. Dr. Stadtmauer and Dr. Friedberg will speak about the role of stem cell transplantation in myeloma and lymphoma, the key research topics for stem cell transplantation, and side effect management and other quality of life issues. For more information or to register, please see the LLS website.
Related Articles:
- ECT-001 Granted Regenerative Medicine Advanced Therapy (RMAT) Designation By U.S. FDA
- Number And Type Of Stem Cell Transplants Carried Out Each Year For Multiple Myeloma Vary Markedly Across U.S. Cancer Centers
- Sustained Complete Response To Initial Treatment Associated With Substantial Survival Benefit In Multiple Myeloma
- Selective Digestive Decontamination May Reduce Risk of Infection In Myeloma Patients Undergoing Autologous Stem Cell Transplants
- Stem Cell Transplantation May Be Underutilized In Multiple Myeloma Patients In Their 80s
Hi Beacon Staff,
Regarding:
"the researchers found that higher rates of osteonecrosis of the jaw were associated with the duration of bisphosphonate therapy as well as the type and cumulative dose of bisphosphonate used."
Would you be able to provide the details on the duration, type and cumulative dose of biphosphonates the researchers found that correlated with higher rates of ONJ? These details were not in the abstract at the link provided.
thanks
I find that the 23% rate of BRONJ experienced by patients with stem cell transplants to be very high compared to previous data printed in the Beacon. There was a previous report of 12% complications for myeloma patients. I agree with Suzierose, it would be interesting to find out more about this research!
Hello suzierose and Nancy,
Thank you very much for your interest in the study and for following up.
Here are more details on the results:
Patients with ONJ had a median duration of bisphosphonate therapy of 55 months, compared to 33.5 months for patients without ONJ.
The risk of developing ONJ was 27.6 percent for patients with a treatment duration above the median of 33.5 months and 12.5 percent for patients with treatment duration below the median.
The median exposure time was 19 months for Zometa (zoledronic acid), 21 months for Aredia (pamidronate), 21.5 months for Boniva (ibandronate), and 4 months for Bonefos (clodronate).
ONJ occurred in 39 percent of patients receiving Zometa, 23 percent receiving Aredia, 15 percent receiving with Boniva, and the one patient who received Bonefos.
The researchers mention that the cumulative dose of Zometa and Aredia was significantly higher in patients who developed ONJ; unfortunately, the doses are only depicted in a graph, which makes it difficult to get the exact numbers.
Beacon Staff,
Thank you so much for these additional details!
Another question in terms of how months were tallied ..
when they give the median duration in months, does the study indicate whether dosing was monthly, every other month or every 3 months for a cummulative median therapy total of 33.5 months?
Also how do you square the median DURATION of 33.5 months, with the significantly lower median EXPOSURE times for each of the 4 agents being less than 33.5 month? i.e. 19, 21, 21.5, 4 months for Z, A, BV and BF, respectively?
There seems to be a significant gap, particularly given the high 23% risk rate when less than 50% of patients had a duration of therapy for the median 33.5 months. Yet ~ half of those who did have above the median developed BRONJ...wow...
Perhaps, I am misunderstanding, but it seems that the risk is very high despite most patients having exposure for a lot less than the median duration.
Thanks Beacon staff and Suzie for this discussion. It's true that sometimes the bisphosphonates are given once a month, or every 2-3 months. I was paranoid about having good dental hygiene when taking them, although I am not sure that helped to prevent BRONJ. At least it was a factor that I had some control over! And I know that my bones are stronger now than at the time of DX.
Hi Nancy!
I am just like you about the bisphosphonates, paranoid. I have had extensive dentalwork including implants, in addition to a mandible jar lytic lesion, so bisphosphonates potential to cause ONJ really has me anxious. It is unsettling to me that the type of bone remodeling of bisphosphonates is not the same as that of normal bone and I worry that can lead to problems if the resultant bone is not as strong as before.
I am also concerned about the very long half-life of over a month and the reports of finding it in the bone after therapy was discontinued more than a decade. All of this makes me cautious about using them. I am very much waiting for the outcome of the Mayo Clinic trial where one arm receives bisphosphonates monthly and the other arm receives it every 3 months.
For now, I think the jury is still out on the risk vs. benefits of bisphosphonate therapy. I wonder if in the end patients will receive a course of therapy say 6 monthly doses and then not have a need for it?
Hi Suzie! Nice to hear from you vis a vis the BP treatments. Another gloomy finding in some women who have been using them for osteoporosis is that sometimes spontaneous fractures occur, for example in the femur. And I don't think that those women would have been given such strong doses as we are, for myeloma. I guess that is something to do with the bone remodelling being different...more crystalline in nature perhaps??
I am just positive that my bones are stronger now, though. For one thing, they were literally crumbling at the time of dx. I could feel it happening, and sure hope I never have to go through that again! Now, despite my best efforts at being careful, I have taken a couple of hard falls on icy walks, and thankfully didn't seem to break anything! That is just a very anecdotal way of testing out one's bone strength I know, but where I live, we do have a long winter, and sometimes one falls! I am due for another skeletal survey soon though. My treatments were individualized in regards to the amount of bone damage I had.
Interesting that there is a big study going on at Mayo. That will be so informative. In my case, I did go from monthly doses, then to every two months, then lastly every three months. My oncologist is very up on all the research findings and tries to take all of these problems into account. when i said earlier that we don't have a dep't of myeloma, perhaps that is not quite correct. There are many myeloma patients here and we are well taken care of actually.
Hope you don't have any problems with the bisphosphonates. i read in one of the articles on the Beacon that smokers may have more problems. If one needs any dental work done, beyond routine cleaning, there is quite a procedure to be followed here at our cancer centre's dental clinic. Luckily for me I didn't need any dental work done over the last four years. Before that I did though, and I wonder if the myeloma was also wearing down my teeth!
"Ten percent of patients relapsed within 6 to 12 years after the transplant, which the researchers described as surprising"
Wow...so they are seeing relapse with allo transplants...very interesting. While disease status at time of allo is an important variable according to the Cox regression analysis, the abstract did not indicate how many of the 5 patients in CR/PR were CR although clearly disease status did impact relapse.
The conclusion is very big news:
"Our data provide additional evidence that, while survival may be extended by reduced intensity allogeneic transplant, ultimately, it may not offer a cure."
The ever elusive cure for myeloma continues.
"Wow…so they are seeing relapse with allo transplants"
Yes, but this results refers to REDUCED intensity allogeneic transplants, which are distinct from the typical HIGH intensity, myeloablative transplants. With allo methods relying on such high intensity, otherwise-lethal chemo, I have seen no evidence of similar relapse rates.
I agree with Joey N. and I think most Doctors would as well. I have put up many links of well respected Doctors saying full allos done early in disease course being curative for younger patients. Unfortunately Reduced Intensity Conditioning is a risk factor for relapses as compared to myeloablative conditioning for allos. RIC's are an attempt to allow more patients to do allos since only a small percentage of myeloma patients are candidates for allos with myeloablative conditioning. ASCT is auto and HSCT is allo.
"In multivariate analysis >1 prior ASCT and "RIC" could be confirmed as independent risk factors. Patients reaching at least a PR prior to HSCT and lacking the latter two risk factor reached an OS of 60% and PFS of 50% with a follow-up till 17.5 years."
"Summarizing the results, we established >1 prior ASCT as an independent risk factor for subsequent HSCT, contradictory to the use of double ASCT as standard therapy, especially in younger patients. Furthermore we saw moderate TRM rates after "myeloablative" HSCT, resulting in a significant better outcome compared to the RIC regimen. This observations raise the question if early and myelablative HSCT might be the key to cure multiple myeloma."
https://www.eventure-online.com/eventure/publicAbstractView.do?id=190223&congressId=5650
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