The results of a recent retrospective study show that the use of novel agents for the treatment of multiple myeloma may not have a negative impact on subse­quent stem cell collection and transplantation.

The study's results stand in contrast to previous research that has suggested that Revlimid, one of the most commonly used novel agents, may have a nega­tive effect on stem cell collection.

Factors in the current study that were found to be associated with stem cell col­lection failure included older age, lower platelet counts prior to stem cell collection, and the use of only a single agent to mobilize stem cells.

The study investigators conclude that their results support recommendations by the International Multiple Myeloma Working Group to use multiple agents to encourage stem cell mobilization, particularly in patients previously treated with Revlimid ^[1] (lenalidomide).

Currently, a common treatment regimen for newly diagnosed myeloma patients under the age of 65 in­cludes three to six cycles of initial therapy with at least one novel agent, such as Revlimid, thalidomide ^[2] (Thalomid), or Velcade ^[3] (bortezomib), followed by high-dose chemotherapy and autologous stem cell trans­plan­ta­tion. In the latter procedure, the patient's stem cells are harvested from their blood before they receive high-dose chemotherapy. The stem cells are later re-infused into the patients to replace any cells that were damaged during high-dose therapy.

According to the researchers, patients should collect at least four to six million stem cells per kilogram of body weight in order to successfully complete the transplant procedure.

Prior research has raised concerns that initial treatment with Revlimid may significantly inhibit subsequent stem cell collection (see related Beacon ^[4] news). Other studies, however, have demonstrated that the nega­tive effect of Revlimid on stem cell collection may be overcome by a stem mobilization using two agents -- granulocyte-colony stimulating factor (G-CSF) combined with cyclophosphamide ^[5] (Cytoxan) -- as opposed to just G-CSF.

The researchers at Memorial Sloan-Kettering Cancer Center in New York City performed a retrospective study evaluating the impact of novel agents on stem cell collection and transplantation. Their objective was to determine the rate of collection failure in patients treated with novel agents and to identify risk factors associated with failure.

The analysis was based on data from 317 myeloma patients with a median age of 57 years who underwent stem cell collection at Memorial Sloan-Kettering between 2000 and 2009.

Overall, 77 percent of patients received at least one novel agent as part of their initial therapy; 49 percent received a thalidomide-based regimen, 24 percent received a Revlimid-based regimen, and 40 percent received a Velcade-based regimen. In addition, 23 percent of patients were treated with older regimens not involving a novel agent.

Patents received a median of five cycles of initial therapy prior to stem cell mobilization and collection. To proceed to transplantation, patients were required to collect five million stem cells per kilogram of body weight. Patients required a median of two stem cell collections to harvest a sufficient number of stem cells for later transplantation. The median time between the completion of initial therapy and start of stem cell mobilization was 1.1 months.

Overall, 13 percent of patients failed to collect a sufficient number of stem cells during the first collection attempt. When the researchers statistically controlled for all variables that could potentially affect stem cell collection success, they found older age, lower platelet counts, and the use of a single-agent G-CSF for mobilization were associated with collection failure.

There was also some indication that previous radiation therapy could affect the number of stem cells collected in the first round of stem cell collection.  However, the variable's impact was not strong enough to have a statistically significant link with actual collection failure.

There was no statistically significant difference in collection failure rates between patients treated with Revlimid and those who were not. Of the patients previously treated with Revlimid, 18 percent were unable to successfully collect enough stem cells for a transplant.  The comparable rates for patients who received initial therapy with Velcade, Velcade and Revlimid combined, or thalidomide were 13 percent, 21 percent, and 7 percent, respectively.

The researchers noted that the majority of patients in this study received a combination of cyclo­phos­pha­mide and G-CSF for stem cell mobilization, which may have countered the potentially negative effects of Revlimid on stem cell collection.

For more information, please see the study in the journal Bone Marrow Transplantation ^[6] (abstract).