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 ^[1] (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 ^[2] (Cytoxan), melphalan ^[3] (Alkeran), and Rev­limid ^[4] (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 ^[5] (bortezomib) and thalidomide ^[6] (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 ^[7] (abstract).