The use of thalidomide (Thalomid) in induction and maintenance therapies for multiple myeloma patients receiving a stem cell transplant resulted in better overall response rates but did not significantly improve overall survival, according to a Phase 3 study recently published in the journal Blood.

In their study, researchers randomly assigned 556 patients to receive three cycles of either vincristine (Oncovin), doxorubicin, and dexamethasone [VAD] or thalidomide, doxorubicin (Adriamycin), and dexamethasone (Decadron) [TAD] as induction therapy. All patients received high-dose melphalan (Alkeran) with an autologous stem cell transplant, followed by maintenance therapy with either alpha-interferon for patients who received VAD or thalidomide for patients who received TAD. Alpha-interferon are naturally occurring proteins that improve the body’s response to infection and slow tumor growth.

The use of thalidomide significantly improved the overall response rate both before and after high-dose therapy with melphalan. For patients who received thalidomide as maintenance, 88 percent achieved at least a partial response, compared to 79 percent of patients who received alpha-interferon as maintenance.

The quality of the response also improved with thalidomide-based induction and maintenance. For patients who received thalidomide as maintenance, 66 percent achieved a very good partial response, compared to 54 percent of patients who received alpha-interferon as maintenance.

Furthermore, the median event-free survival (EFS) – the length of time after treatment that a patient does not experience a complication of myeloma – for patients randomized to thalidomide was 34 months, compared to 22 months for patients who did not receive thalidomide. The median progression-free survival (PFS) – the length of time after treatment that a patient does not experience disease progression – for patients randomized to thalidomide was 34 months, compared to 25 months for patients who did not receive thalidomide.

Although thalidomide improved overall response rates and extended EFS and PFS, it did not result in a statistically significant lengthened overall survival time because patients randomized to thalidomide experienced shorter median survival times after progression/relapse (20 months) than patients who did not receive thalidomide as induction or maintenance therapy (31 months).

The authors of the study hypothesized that this may be due to the discrepancy in the usage of thalidomide after progression/relapse – 64 percent of refractory/relapsed patients from the VAD regimen received thalidomide during salvage therapy, while only 38 percent of patients with progression/relapse from the TAD regimen received salvage therapy with thalidomide.

The study authors also presented an alternate explanation, in which aggressive drug-resistant clones may have generated relapses after prolonged exposure to thalidomide.

The overall results suggest that the use of thalidomide as induction and maintenance therapy is a promising approach for treatment of myeloma. However, it is not yet known how prior exposure to thalidomide as induction therapy impacts its efficacy as maintenance therapy. The authors of the study propose that thalidomide should only be prescribed for a limited duration as post-induction therapy to avoid a relapse caused by resistance to the drug. 

For more information, please see the study in the journal Blood (abstract) or the clinical trial description.