A recent study showed that initial treatment of multiple myeloma with a combination of cyclophosphamide and thalidomide negatively impacts a patient’s ability to collect stem cells for transplant.

Physicians were able to collect almost 50 percent fewer stem cells from patients treated with cyclophosphamide and thalidomide (Thalomid) compared to patients treated with other commonly used myeloma treatments. This combination therapy may prevent stem cells from moving from the bone marrow into the circulating blood, where they are harvested for stem cell transplantation.

Treatment of multiple myeloma typically begins with a combination of drugs that specifically target myeloma cells, known as induction therapy. For young myeloma patients, this treatment regimen is usually followed by autologous stem cell transplantation, in which a patient’s stem cells are harvested and then transplanted back later in the patient’s treatment.

Some drugs, although effective in targeting myeloma cells, are not used in induction therapy for transplant-eligible patients because they reduce the patient’s stem cell count and inhibit stem cell mobilization to the blood, where they can be collected. If not enough stem cells can be harvested, then the patient is unable to receive stem cell transplantation.

Autologous stem cell transplantation has been shown to increase survival and has been an integral part of multiple myeloma treatment in relapsed patients. For patients who are transplant-eligible, physicians, therefore, carefully consider the impact that induction therapies have on stem cell collection.

When used alone and in other combination therapies, thalidomide and cyclophosphamide do not usually disrupt the stem cell harvesting process. However, this study investigated the effect of a combination of these two drugs on stem cell mobilization in multiple myeloma patients.

A group of 67 patients received an induction therapy of oral cyclophosphamide, thalidomide, and dexamethasone (Decadron) (CTD). This group was compared to a control group of 69 patients who received induction therapy with either a vincristine-doxorubicin (Adriamycin)-dexamethasone combination or an oral idarubicin-dexamethasone combination. Both of these control therapies are known to rarely have an effect on stem cell mobilization.

After the completion of induction treatment, patients received stem cell mobilization therapy of oral cyclophosphamide and G-CSF until stem cell collection was complete.

The total number of stem cells collected from patients who received the CTD combination (median 5.0 x 10⁶ cells/kg) was significantly lower than the number of stem cells collected from the patients in the control group (median 9.8 x 10⁶ cells/kg). When evaluated on a per-day basis, the number of stem cells harvested on each day of mobilization was also significantly lower for patients who received CTD.

In the CTD group, almost 40 percent of patients failed to meet the standard target number of stem cells necessary for two stem cell transplants (4 x 10⁶ cells/kg), whereas only 16 percent of the control group did not meet this requirement.

Additionally, 25 percent of patients who received CTD failed to meet even the minimum stem cell count necessary for one transplant (2 x 10⁶ cells/kg), whereas only 8 percent of patients in the control group did not meet the minimum.

An inability to harvest stem cells can sometimes be the result of old age or a higher number of induction treatment cycles. However, it was determined in the study that the age of the participants and the number of induction treatment cycles they underwent did not make a significant difference in the success or failure of stem cell collection.

It has been shown through numerous other studies that thalidomide and cyclophosphamide, when used alone, have little-to-no effect on stem cell mobilization. However, the results of this study suggest that the combination of these two drugs is directly responsible for the negative impact of CTD therapy on stem cell mobilization and subsequent collection.

“We do not really know the precise mechanism by which the combination causes failure of mobilization,” said Dr. Amin Rahemtulla of the Imperial College in London and one of the authors of the study. “We have not studied this.”

As treatment strategies for multiple myeloma shift toward the use of combination therapies, this study highlights the importance of considering the effects drugs may elicit in combination in addition to the effects they elicit independently.

“We should be vigilant about the effect of new treatment regimens on stem cell mobilization,” stated Dr. Rahemtulla.

For more information, please see the study in Nature (abstract) or a related Beacon article about the efficacy of CTD followed by stem cell transplantation.