Mozobil Associated With An Increased Risk Of Secondary Cancer
A new study indicates that patients treated with Mozobil prior to a stem cell transplant may have an increased risk of developing a secondary cancer.
The patients in the new study were being treated for either lymphoma or myeloma. They were given Mozobil (plerixafor) to improve their chances of harvesting enough stem cells to allow them to undergo an autologous (own) stem cell transplant.
All patients in the study were treated with Mozobil, and all had previously failed to collect enough stem cells for a transplant.
Among the patients in the study who were able to proceed to a stem cell transplant, there was a higher than expected risk of secondary cancer in the form of either myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).
Specifically, the rate of secondary MDS and AML was about twice as high as what would have been expected based on previous research on secondary cancer in stem cell transplant patients.
MDS is a group of blood disorders marked by ineffective production of blood cells. MDS often progresses to AML, a disease in which the body overproduces abnormal white blood cells.
Unfortunately, treatment options are generally limited for patients who develop MDS or AML after a stem cell transplant.
It is unclear what caused the increased risk of secondary MDS and AML observed in the new study.
One possible explanation is that Mozobil itself played a role in the development of MDS and AML.
Another possible explanation is that the patients in the study – all of whom had failed at least once to harvest enough stem cells without Mozobil – were more likely to develop MDS and AML than patients able to harvest enough stem cells without the drug.
The lead author of the new study, Dr. Abhinav Deol of the Karmanos Cancer Institute in Detroit, believes it is too early to advise any change in the use of Mozobil. “With the current information from our study, we do not recommend any change in the use of [Mozobil],” he told The Beacon.
However, Dr. Deol does recommend that patients who have been treated with Mozobil be watched carefully for signs of MDS or AML.
If further studies establish a link between Mozobil and secondary MDS and AML, the drug could become yet another treatment myeloma patients often receive that has a known risk of secondary cancer.
U.S. drug regulators, for example, currently require warnings about an increased risk of secondary cancer in the official prescribing information for cyclophosphamide (Cytoxan), melphalan (Alkeran), and Revlimid (lenalidomide).
Background
An autologous stem cell transplant is a common treatment option for myeloma patients. The transplant process starts with a patient’s own stem cells being collected. Next, the patient receives the actual treatment that is part of the process, which is high-dose chemotherapy. Finally, the previously collected stem cells are re-infused into the patient to replace the healthy cells destroyed by chemotherapy.
In the past, about 5 percent to 10 percent of transplant-eligible patients were unable to harvest enough stem cells to allow them to proceed to a transplant, according to the authors of the new study.
In late 2008, however, the U.S. Food and Drug Administration (FDA) approved Mozobil as a treatment to help patients who might otherwise be unable to harvest a sufficient number of stem cells for a transplant.
The drug, which is marketed by Genzyme, a subsidiary of Sanofi-Aventis (NYSE:SNY), helps move stem cells out of the bone marrow into the bloodstream, where they can be harvested.
Although previous studies have shown that Mozobil aids in the stem cell harvesting process, the authors of the current study state that little is known about the long-term effects of treatment with Mozobil.
Thus, the investigators – all of whom are affiliated with the Karmanos Cancer Institute – decided to study the long-term impact of Mozobil treatment in 49 patients who received the drug between 2006 and 2009.
Details Of The Study
The patients in the Karmanos study were treated with Mozobil as part of a compassionate use clinical trial, which permitted use of the drug prior to its final approval by the FDA.
Of the 49 patients in the study, 17 (35 percent) had multiple myeloma, and the rest had lymphoma. The median age of the patients was 64 years.
All 49 patients had failed at least once to harvest sufficient stem cells for a transplant. One quarter of the patients had tried, and failed, two or more times to collect enough stem cells for a transplant.
Among the myeloma patients in the study, 41 percent had been treated with Revlimid at some point, and 18 percent had previously received an autologous transplant.
Eventually, 43 of the 49 patients in the study – including 16 of the 17 myeloma patients – were able to proceed to an autologous stem cell transplant after collecting a sufficient number of stem cells prior to transplantation.
Risk Of Secondary MDS And AML
After a median follow-up time of 42 months, five of the 43 patients (12 percent) developed a secondary case of either MDS (4 patients) or AML (1 patient). The median survival of these patients after their MDS or AML diagnosis was 10 months.
Of the five patients who developed secondary MDS or AML, four were lymphoma patients, and one was a myeloma patient. The myeloma patient had previously received a stem cell transplant, which was not successful, and then was treated with Velcade (bortezomib) and thalidomide (Thalomid) before receiving a second transplant during the current study.
There are at least two previous studies that can be used to put the risk of secondary MDS and AML observed in this study into perspective.
One previous study found that, among all the patients who received a transplant during the study, 3 percent eventually developed either MDS or AML at a median follow-up of five years.
Another study, however, found the same rate to be almost 20 percent after a median follow-up of 10 years.
Dr. Deol, the lead author of the current study, believes the results of the new study indicate that the risk of transplant patients treated with Mozobil developing secondary MDS or AML is probably “about double” what has been seen in previous studies.
Potential Causes Of The Secondary MDS And AML
Dr. Deol and his collaborators also believe there are two broad explanations which could account for the higher risk of secondary MDS and AML seen in their study.
One possibility is that the patients in the study were more inclined than typical transplant patients to develop secondary MDS and AML. The fact that a patient is unable to harvest enough stem cells on their own could be a sign that their stem cell production process is abnormal or damaged, making the patient more likely to develop MDS or AML.
However, in regard to this potential explanation, the authors note that none of the patients in their study who developed MDS or AML had previously been treated with radiation therapy. Such therapy is often believed to make a cancer patient more likely to develop secondary MDS or AML.
The other possible explanation is that Mozobil itself played a role in the increased risk of secondary MDS and AML seen in the study. Mozobil, for example, may tend to mobilize damaged stem cells rather than healthy ones. Or the drug may damage some of the stem cells that it mobilizes.
Further research will be necessary, the investigators say, to more accurately determine to what extent – and why – Mozobil-treated patients are at an increased risk of developing secondary MDS or AML.
For more information, please refer to the study in Bone Marrow Transplantation (abstract).
Related Articles:
- Selective Digestive Decontamination May Reduce Risk of Infection In Myeloma Patients Undergoing Autologous Stem Cell Transplants
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Stem Cell Transplantation May Be Underutilized In Multiple Myeloma Patients In Their 80s
- Number And Type Of Stem Cell Transplants Carried Out Each Year For Multiple Myeloma Vary Markedly Across U.S. Cancer Centers
- Researchers Shed More Light On Risk Of MGUS In Close Relatives Of People With Multiple Myeloma
This is an exceptionally scary finding for me. Hopefully the number of participants were too small to make it scientifically sound. I tried three time to harvest stem cells with Mozobil as an assist. The fourth time the combo of hyperbaric chamber and Mozobil worked. That's a lot of a medicine that leads to a secondary cancer.
Hi Gary,
Thanks for your comment.
The study is a somewhat small one, but it's almost certainly "sound" otherwise.
That said, remember ... the patients who developed secondary MDS or AML all received a transplant. Thus, all that can be said based on this study is that patients who receive Mozobil and then go on to receive a transplant appear to be at a greater risk of getting secondary MDS/AML. The data do not speak to whether or not Mozobil, without a stem cell transplant, is also associated with a greater risk of secondary MDS/AML.
Dear Beacon Staff,
Has the role of acetaminophen and secondary cancers been studied with regards to myeloma patients?
A study came out in 2011 that showed a two fold increase in hematological malignancies in those that use acetaminophen 4 times a week or more (http://www.ncbi.nlm.nih.gov/pubmed/21555699)
Since those of us with multiple myeloma are often given acetaminophen in the form of Tylenol, Vicodan, Norco etc, is it something worth trying to avoid if possible?
We already have a blood disorder, I would think we have systems that are naturally sensitive to certain environmental conditions, ie too much acetaminophen. If the general population has a two fold increase in blood malignancies related to the use of acetaminophen, could myeloma patients be adding on another level of risk to secondary cancers by acetaminophen?
Hi Stann,
Thanks for your question.
We've not been able to find any studies that look into the use of Tylenol (acetaminophen, paracetamol) among myeloma patients and whether or not it is linked to a higher risk of secondary cancers.
However, given the study you cite as well as other research that has looked into the potential link between Tylenol and blood cancers, we can see the logic behind recommending that myeloma patients avoid Tylenol or Tylenol-containing painkillers such as Percocet and Vicodin.
The best thing to do is to discuss the issue with your doctor and see whether they agree that the potential benefits from switching away from Tylenol-containing pain killers outweigh the costs (particularly the side effects associated with greater dependence on aspirin- or opiate-containing pain killers).
Hi Guys
After reading this article, I have a question. How many shots of Mozobil did these therapies involve ? When I did my transplant, a little more than 2 years ago, I had to have 1 shot of Mozobil the evening of my first collection. I didn't produce enough cells the first day for 2 transplants, but after the shot they got enough cells for more than 2 transplants the next day. I am just wondering How many shots it takes for there to be a problem. thanks dee
Thanks for your question, Deidre.
Patients in this study could receive up to four doses of Mozobil.
The article does not say, however, how many doses of Mozobil were given to the five patients in the study who developed a secondary cancer.
Among all the 43 patients in the study who received a stem cell transplant after being treated with Mozobil, at least 17 of the patients received only one dose of Mozobil.
Beyond that, the article doesn't really give enough information to determine exactly how many patients who got a transplant received 1, 2, 3, or 4 doses of Mozobil.
If we are able to find out more information on this subject, we'll let you and the rest of our readers know.
To clarify a few things,
1. Development of secondary MDS/AML post auto transplant is a well recognized complication of auto transplant
1. There was one pt with myeloma who developed MDS, but had history of prior transplant and was treated with other chemotherapeutic agents prior to mobilization with Plerixafor. The other 4 pts had previous treatment for NHL with drugs which are known to cause secondary cancers.
2. Plerixafor use permitted these patients to proceed to an auto transplant which would not have been an option for treatment for these patients in the past
3. The cause of development of MDS/AML in these patients cannot be attributed one single event and was in all probability multifactorial,needs further investigation.
Thank you, Dr. Deol, for the additional comments regarding this study.
As Dr. Deol mentioned -- and as was noted in our review of this new research -- secondary cancers have traditionally been observed among patients who have had stem cell transplants.
What was different about the patient's in Dr. Deol's study, compared to those in previous studies looking at transplants and secondary cancer, is that all of the patients in this new study not only received transplants, but those transplants were preceded by treatment with Mozobil.
It is therefore notable that Dr. Deol and his colleagues found, as they write in their paper, that the “incidence of secondary MDS/AML after ASCT … observed in this report is higher than expected …” – perhaps twice as high, according to the estimate Dr. Deol provided The Beacon (which is quoted above).
It is not clear at this time why the rate of secondary MDS/AML was higher in this group of patients. As The Beacon explained in the article above, and as Dr. Deol notes in his comments, there are a number of potential explanations.
This is why The Beacon made an explicit decision in our article and its headline to avoid stating that Mozobil “causes,” “leads to,” or “results in” higher rates of secondary cancer.
All that can be said at this point is that, in this group of patients, all of whom had been treated with Mozobil, there was a higher than expected rate of secondary MDS/AML. Treatment with Mozobil was associated with, but not necessarily the cause of, a higher than expected level of secondary cancers.
Thanks for differentiating associations from causality, a common error of study interpretations. Also, the benefits of successful harvesting and subsequent auto transplants need to be balanced with the risks, both of which are still rather vague. So more research is needed. It does appear however that with newer novel agent therapies, the use of ASCT will decrease.
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