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Study Questions Conventional Wisdom On Revlimid And Stem Cell Collection

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Published: May 3, 2013 7:33 pm

A recent retrospective study finds that initial treatment with Revlimid may not prevent myeloma patients from collecting enough stem cells for transplantation.

Many of the study’s results confirm the findings of previous research, which has shown that Revlimid (lenalidomide) reduces a patient’s ability to mobilize stem cells for stem cell collection (see related Beacon news).

However, only 2 percent of the patients in the new study were unable to mobilize enough stem cells for at least a single transplant, and this low overall rate of mobilization failure was the same in patients who had, or had not, been previously treated with Revlimid.

Furthermore, the 2-percent rate of mobilization failure in Revlimid-treated patients was observed despite the fact that more than 40 percent of those patients received five or more cycles of treatment with Revlimid.

These findings, the authors argue, call into question the current International Myeloma Working Group (IMWG) recommendation that myeloma patients initially being treated with Revlimid undergo stem cell col­lec­tion within four cycles of therapy to reduce the chance of stem cell collection failure (see related Beacon news).

Nevertheless, the investigators recommend that the impact of Revlimid on stem cell collection and transplantation be evaluated in prospective clinical trials.

Background

A common approach to treating newly diagnosed myeloma patients under the age of 65 begins with novel agent-based initial therapy followed by high-dose chemotherapy and autologous stem cell transplantation.

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- Stem cell collection

During the transplant procedure, a patient’s stem cells are collected prior to high-dose chemotherapy and then later re-infused into the patient to replace the cells that were destroyed during chemotherapy.

To successfully prepare for a transplant, physicians typically aim to collect at least four to six million stem cells per kilogram of the patient’s body weight.

Earlier retrospective studies have suggested that treatment with Revlimid may lead to greater risks of stem cell collection failure. However, a more recent analysis conducted at Memorial Sloan-Kettering Cancer Center in New York City found that Revlimid may not hinder stem cell collection (see related Beacon news).

The effect of Revlimid on stem cell collection and transplantation has yet to be examined in prospective clinical trials.

Study Design

Researchers at the Karmanos Cancer Institute in Detroit conducted a retrospective analysis of the effect of Revlimid exposure on subsequent stem cell collection and transplantation. In particular, they sought to determine the rate of collection failure in patients treated with and without Revlimid who received granulocyte colony-stimulating factor (G-CSF) as a mobilization agent.

Neupogen (filgrastim) and Neulasta (pegfilgrastim) are versions of G-CSF commonly used in the U.S.

The analysis in the current study was based on data from 319 multiple myeloma patients with a median age of 58 years who underwent stem cell collection at the Karmanos Cancer Institute between 2007 and 2011. Patients who had previously received a stem cell transplant were not included in the analysis.

Of patients included in the analysis, 58 percent received Revlimid-based therapy, defined as at least one complete cycle (21 consecutive days) of a treatment regimen including Revlimid, and 42 percent had no prior exposure to Revlimid.

Two-thirds of the patients who were initially treated with Revlimid received one initial treatment before stem cell collection, which consisted of Revlimid plus dexamethasone (Decadron) or Revlimid, Velcade (bortezo­mib), and dexamethasone. Those who received more then one initial therapy most frequently received Revlimid plus dexamethasone preceded or followed by Velcade-based therapy.

Of the patients who did not initially receive Revlimid, 77 percent received one initial treatment, which most frequently consisted of Velcade plus dexamethasone.

Patients in the Revlimid-treated group had received a median of four treatment cycles before collecting stem cells, and patients with no Revlimid exposure had received a median of five treatment cycles.

Overall, 80 percent of patients had their stem cells mobilized with G-CSF alone, 10 percent received G-CSF and Mozobil (plerixafor), 9 percent received G-CSF and cyclophosphamide (Cytoxan), and 1 percent received G-CSF and sargramostim (Leukine).

Initial stem cell collection failure was defined as the inability to collect at least two million stem cells per kilogram of body weight in three days.

According to the researchers, an adequate target for collection is at least four million stem cells per kilogram of body weight, which is the minimum number of stem cells required for two transplants.

Study Results

Many of the study’s results mirror those of other researchers who have found a negative impact of Revlimid treatment on stem cell collection.

For example, the researchers found that a higher share of Revlimid-treated patients (9 percent) failed to collect a sufficient number of stem cells during their first collection attempt compared to patients with no Revlimid exposure (5 percent).  This difference, however, was not statistically significant.

The researchers also found an association between Revlimid exposure and lower stem cell yield. The median number of stem cells collected in the Revlimid-treated group was lower (6.34 million cells/kg) compared to that of the group with no exposure to Revlimid (7.52 million cells/kg).

Additionally, Revlimid-treated patients required a median of two collection sessions to collect an adequate number of stem cells, compared to one collection session in patients not treated with Revlimid.

There also was a negative association between stem cell yield and the number of Revlimid treatment cycles received.  Patients who received less than five cycles of treatment had a noticeably higher yield than patients treated with five or more cycles.

This finding was reflected in the fact that, among the patients with previous Revlimid exposure who failed to collect a sufficient number of stem cells during their first collection attempt, 75 percent had received more than four cycles of Revlimid.

Nevertheless, the Karmanos researchers believe their results – taken as a whole – argue against limiting treatment with Revlimid due to concerns about its potential impact on stem cell collection.

They note, for example, that of the 22 patients (7 percent) in their study who failed their initial collection, 16 eventually were able to mobilize enough stem cells for at least a single transplant.

Or, looking at it another way, only 2 percent of the patients in the study were unable to collect a sufficient number of stem cells for a single transplant.

Moreover, this overall failure rate of 2 percent was the same in both the Revlimid-treated group of patients and the patients with no previous Revlimid exposure.  This occurred despite the fact that 42 percent of the Revlimid-treated patients had received more than four cycles of Revlimid.

Finally, the researchers found that there was no difference between the Revlimid-treated patients and other patients in how long it took for patients’ white blood cell and platelet counts to recover after transplantation.

Thus, although the researchers recognize that Revlimid treatment did have an impact on stem cell collection among the patients in their study, they are not convinced the impact was significant enough to have practical implications.

They therefore suggest a reevaluation of the current guidelines recommending that patients being treated with Revlimid undergo stem cell collection after no more than four cycles of treatment.

Those guidelines, the authors indicate, may unnecessarily be causing a number of patients to have their stem cells collected before the patients have been able to achieve the deepest possible response to treatment.

For more information, please see the study in the journal Supportive Care in Cancer (abstract).

Photo by Nissim Benvenisty on Public Library of Science – some rights reserved.
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  • Gary said:

    First and second line of this message seem inconsistent. Which is true?