The paired use of novel drug agents and autologous stem cell transplantation (ASCT) may not be as effective as formerly believed, according to the June issue of the journal Blood.

Treatment for multiple myeloma commonly integrates high dose therapy of novel drug agents with ASCT. However, an article printed in Blood shows that initial treatment with Revlimid (lenalidomide), one of the novel drug agents, corresponds with inhibition of stem cell mobilization and collection for ASCT.

The introduction of novel drug agents, including thalidomide (Thalomid), Revlimid, and Velcade (bortezomib), has rapidly advanced the methods for treating multiple myeloma, which had previously used combinations of vincristine, doxorubicin (Adriamycin), and dexamethasone (Decadron), known as VAD. Nearly all newly diagnosed myeloma patients are now initially treated with high dose therapy of the novel agents, which has generally resulted in high response rates. However, despite the current efficacy of these therapies, the long-term effect is still unknown due to the lack of long-term follow up of patients treated with these novel agents. As a result, ASCT remains an integral component of myeloma therapy, and an increasing number of patients are undergoing ASCTs in combination with treatment of novel agents.

The traditional approach to treating newly diagnosed myeloma patients who are eligible for ASCT has prescribed initial therapy of four to six cycles of a non-alkylating drug regimen, followed by stem cell collection and high dose therapy. The drug regimen specifies treatment with non-alkylating agents because alkylating agents (which add an alkyl group) damage DNA and are therefore harmful to both healthy and cancerous cells. After the initial drug regimen has ended, the patient’s stem cells are collected in preparation for ASCT. Previous studies have determined that ASCTs performed with less than 2 x 10⁶ stem cells/kg, which is less than half of the average number collected, negatively impact the success of the engraftment.

Although several key factors, such as patient age, are recognized as inhibitors to stem cell collection, the impact of novel drug agents was unknown prior to the Blood article. The research, which evaluated data from Phase 2 and 3 clinical trials, indicated that initial therapy with thalidomide had limited impact on stem cell collection. Likewise, stem cell harvest was not impacted by initial therapy with Velcade.

Different results were obtained for Revlimid, for which a known side effect is myelosuppression, a condition that reduces the number of red blood cells, white blood cells, and platelets. Not surprisingly, initial therapy with Revlimid was the most significant factor influencing stem cell mobilization and collection, with additional factors including patient age and the duration of Revlimid therapy. The exact mechanism for Revlimid-associated inhibition is not yet clear, but it is likely that treatment with Revlimid results in increased levels of granulocyte colony-stimulating factor (G-CSF). G-CSF stimulates the bone marrow to produce granulocytes and stem cells, and higher G-CSF levels might lead to tachyphylaxis, a rapid decrease in the response to a drug after repeated doses over a short period of time.

Given the data produced in this study, a panel of experts organized by the International Myeloma Foundation recommended early stem cell mobilization for stem cell transplantation candidates.

For more information, see the article (abstract) in the June issue of the journal Blood.