Mozobil May Help Revlimid-Treated Myeloma Patients Collect Enough Stem Cells For Transplantation
A recent study suggests that Mozobil helps multiple myeloma patients with prior exposure to Revlimid collect enough stem cells for transplantation.
The study investigators conclude that stem cell mobilization with the aid of a growth factor plus Mozobil (plerixafor) is an effective upfront approach for multiple myeloma patients who plan to undergo a transplant, regardless of previous Revlimid (lenalidomide) exposure.
“With growth factor and preemptive Mozobil, virtually all patients with multiple myeloma can have successful stem cell collection,” said Dr. Luciano Jose Costa of the Medical University of South Carolina, and lead author of the study. He added, “If growth factor and preemptive Mozobil is used for mobilization, the negative effect of Revlimid can be offset.”
However, the investigators also point out that this is a retrospective study, and that randomized trials are needed to further evaluate the efficacy of Mozobil in Revlimid-treated patients.
Additionally, the researchers note that while Mozobil helped patients collect enough stem cells for transplantation (at least two million stem cells per kilogram of body weight), the amount of stem cells collected might still be less than optimal for a successful transplant. Previous studies have suggested that undergoing transplantation with less than five million stem cells per kilogram has been associated with delayed recovery.
“It would take a randomized prospective trial comparing different cell doses and analyzed by intent-to-treat to answer the question if cell dose matters,” said Dr. Costa.
Autologous stem cell transplantation is a standard treatment option for younger newly diagnosed myeloma patients. In this procedure, a patient’s own stem cells are collected and later re-infused into the body to replace healthy stem cells killed off during chemotherapy.
A minimum of two million stem cells per kilogram of body weight must be harvested in order to perform one transplant. Prior to collection, growth factors, such as Neupogen (filgrastim) and Neulasta (pegfilgrastim), are administered to make the bone marrow produce more stem cells. These stem cells then mobilize from the bone marrow to the circulating blood and are collected to be used for the transplant.
However, Revlimid has been shown to negatively affect stem cell collection, preventing patients from harvesting enough cells for a transplant. Prior studies have demonstrated mobilization failure rates of up to 25 percent for patients treated with Revlimid, compared to 5 percent to 10 percent for myeloma patients overall.
A recent Phase 3 study showed that the addition of Mozobil starting on day 4 of a mobilization procedure using Neuopogen reduced the number of stem cell collection days needed compared to Neupogen alone. Additionally, preliminary studies suggest that patients with prior Revlimid exposure who fail mobilization with a growth factor alone will often mobilize a sufficient number of stem cells when aided with a growth factor plus Mozobil.
Based on these findings, researchers at the Medical University of South Carolina sought to determine whether Mozobil would overcome the negative effect of Revlimid on stem cell mobilization.
The researchers retrospectively analyzed data from 89 myeloma patients undergoing their first mobilization. Among the patients included in the study, 45 percent had no prior exposure to Revlimid (Revlimid-naïve), 34 percent previously had received one to four cycles of Revlimid, and 21 percent had exposure to more than four cycles of Revlimid.
During mobilization, each patient received either 10 μg/kg of Neupogen daily for four days or 12 mg of Neulasta on day 1 of the mobilization process. On day 4, a blood sample was taken to measure the concentration of stem cells in their blood.
If the concentration was high enough (14 stem cells per mm3 of blood for a single transplant, 25 stem cells per mm3 for two transplants), stem cell collection started immediately until the target number of stem cells was collected or until the patient underwent four days of collection.
If the concentration was not high enough, patients received 240 μg/kg of Mozobil on day 4 and began harvesting cells on day 5. Daily Neupogen and Mozobil were continued until the target stem cell yield was met or until patients underwent four days of collection.
The typical collection target was six million stem cells/kg, which would allow a patient to undergo two transplants. Ninety-five percent of Revlimid-naïve patients, 83 percent of patients who received one to four cycles of prior Revlimid, and 74 percent of patients with more than four cycles of prior Revlimid aimed to collect six million stem cells/kg; the remainder aimed for a target of three million stem cells/kg.
Prior exposure to Revlimid was shown to be directly associated with reduced stem cell concentrations prior to collection. On the fourth day of mobilization, the median concentration for the Revlimid-naïve group (27 stem cells per mm3 of blood) was higher than that of patients who received one to four cycles of Revlimid (14.5 stem cells per mm3) and more than four cycles of Revlimid (10 stem cells per mm3).
The lower stem cell concentrations observed in patients with greater exposure to Revlimid led to higher rates of Mozobil usage. Forty-five percent of Revlimid-naïve patients, 63 percent of patients with one to four cycles of Revlimid, and 84 percent of patients who underwent more than four cycles of Revlimid received Mozobil prior to stem cell collection.
Stem cell collection was completed after a median of 1.5 days of collection for the Revlimid-naïve group as well as the group who received one to four cycles of Revlimid, and 2 days for the group that received more than four cycles of Revlimid.
The median yield harvested was 8 million stem cells/kg in the Revlimid-naïve group, 7.4 million stem cells/kg in patients with one to four prior cycles of Revlimid, and 7 million stem cells/kg in patients with more than four prior cycles of Revlimid. All patients in the Revlimid-naïve group met their mobilization targets, compared to those treated with one to four cycles of Revlimid (90 percent) and those treated with more than four cycles of Revlimid (79 percent).
Notably, every patient was able to collect the minimum number of stem cells required to undergo one transplant, and none required remobilization.
For more information, please see the study in Bone Marrow Transplant (abstract).
Related Articles:
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
- Stem Cell Transplantation May Be Underutilized In Multiple Myeloma Patients In Their 80s
- Selective Digestive Decontamination May Reduce Risk of Infection In Myeloma Patients Undergoing Autologous Stem Cell Transplants
Why am I so incredibly exceptionally unique. I am revlamid naive. I tried three times to harvest stem cells with Neupogen and Mozobil. No luck but lots of expense. Finally, I entered the world of hyperbaric chambers and got some cells with Mozobil still short of the desired 5,000,000.00. I tried again with no luck at all. Perhaps there is something in the water in South Carolina.
Seriously,would it be worth a trip?
Hi Gary,
I feel you!
Looks like you are in the 5-10% of MM patients based on what the article states:
"Prior studies have demonstrated mobilization failure rates of up to 25 percent for patients treated with Revlimid, compared to 5 percent to 10 percent for myeloma patients overall."
I am a 5% MM patient too in terms of cytogenetics.
Sometimes the numbers just aren't on our side.
There could be something to the water in SC as all my paternal relatives that are from there died of cancer.
Or is it in the soil?
When I had my stem cells harvested in late 2009, Revlimid was not yet approved for patients here. Even when it was approved, it was not for a 'first line' of treatment. so of course I hadn't had it yet. (I took it later for 'maintenance'). My harvesting went fine, although of course as we discussed earlier this week, not without some distress, both physically and emotionally. So I wonder if now that it has been realized that Revlimid may slow down stem cell mobilization, why it would be part of an induction treatment? Perhaps this has to do with the PN issues. It must be difficult for oncologists to choose what treatments to start off their patients with at diagnosis.
I can attest to the findings of this report. I had been on Revlimid for 5 cycles when I had my stem cell collection done. Several days of neupogen and all I collected the first day was .5M/KG. Had a mozobil injection the first evening, next day collected 5M/KG. One more mozobil injection, and the next day 4M/KG. All together, 3 days and 9M/KG. Without the mozobil, there's no way I would have collected enough stem cells.
I think there must be an error here when they say you need 2 million stem cells per kilo of weight for an autologous transplant. Our center goes for about 3-4 million per transplant. At the rate they quote in this article, NOONE could harvest enough cells to transplant.
Hi Denise,
Perhaps the patients that receive ASCT at your center have delayed recovery?
The article says:
"Previous studies have suggested that undergoing transplantation with less than five million stem cells per kilogram has been associated with delayed recovery."
Denise,
I'm not an expert, but I believe that some centers and medical professional say things like "Our target is to harvest 3 million stem cells" when they really mean to say "Our target is to harvest 3 million stem cells per kilogram." They just leave out the "per kilogram" part because it may seem unnecessarily technical.
Hi folks! I head up a Stem Cell processing lab in the UK, and you may wish to know this: (1) an adequate dose for a stem cell transplant is 2 x 10^6 CD34+ cells/kG. This is in black & white the UK guildeines. Many transplant centres aim for a target 4 x 10^6/kG in order to have sufficient material for a double (i.e. repeat) transplant, before considering elligibility for an allogeneic transplant using stem cells from either a related or unrelated donor. (2) G-CSF alone or with Cyclophosphamide fails to mobilise stem cells in ~20% of patients. (3) Of the latter, approx. three quarters WILL mobilise CD34+ cells after G-CSF plus Plerixafor provided that some stem cells appeared in the first attempt at mobilisation... which means that a hard core 5% of myeloma pateinst currently DO NOT mobilise their own stem cells. Tough medicine for tghose suferers, sorry to say.
I to was on Revlimid for 3 cycles and then to the Neupogen for 4 days and not enough for transplant. Then two shots of Mozobil and bang... my cells tripled and I was able to transplant. But there was a lot of breath holding. I had taken the Neupogen self injection for the 3 days prior to harvest. They said that they were able to harvest enough for two transplants. I have the rest set aside if I need another sct. I was part of a study that had 3 parts. Part 1 was just a stc and no medication. Part 2 was stc and maintenance with Revlimid 15 mg. Part 3 was a double stc with no medication. I got part B and started on the Revlimid right after stc. But was not able to tolerate the side effects. But the Mozobil was what made my cells harvest-able. I don't know why but I am glad they did.