At the 2008 meeting of the American Society of Hematology in December there were several oral presentations on the outcomes of newly diagnosed patients with multiple myeloma where Revlimid® (lenalidomide) was incorporated into the induction or maintenance regimens.

Revlimid is an orally administered derivative of thalidomide, which is a very active agent for the treatment of refractory multiple myeloma. Revlimid is reported to have less toxicity than thalidomide but retains significant antimyeloma effects. Revlimid is currently being evaluated for the initial treatment of patients with multiple myeloma. Remission induction strategies for patients eligible for autologous stem cell transplantation have to allow for successful collection of peripheral blood stem cells; this, however, is not a consideration for ineligible patients.

Revlimid and Dexamethasone for Induction

The most commonly studied Revlimid regimen for the initial treatment of patients with myeloma involves the addition of dexamethasone. At ASH 2007 researchers affiliated with the Eastern Cooperative Group (Study E4A03) reported that Revlimid plus high-dose dexamethasone was associated with a higher death rate than seen following Revlimid and low-dose dexamethasone for initial treatment of patients with multiple myeloma. Overall response rates to Revlimid and dexamethasone were 70-80% with complete or very good partial remission in over half of all patients. At ASH 2008 researchers involved in a multi-center trial reported that time to tumor progression and progression-free survival in patients receiving Revlimid and dexamethasone were worse in patients with adverse cytogenetics compared with patients with standard risk features.[i] Median progression-free survival was 18.5 months for 16 patients with adverse cytogenetics compared with 36.5 months for 84 patients with standard risk features. However, because of the success of salvage therapy, there were no differences in overall survival between the good and bad risk groups.

Revlimid, Cytoxan, and Dexamethasone for Induction

Researchers from the Mayo Clinic reported an overall response rate of 83% for 53 patients with newly diagnosed multiple myeloma with the combination of Revlimid, Cytoxan® (cyclophosphamide), and dexamethasone.[ii] The complete and very good partial remission rate was 40%. This regimen appeared to be well tolerated.

Relvimid, Velcade, and Dexamethasone for Induction

Researchers affiliated with a multicenter U.S. clinical trial reported the results of a Phase I/II evaluation of induction with the combination of Revlimid, Velcade, and dexamethasone in previously untreated patients with myeloma with high-risk features.[iii] There were 63 patients in this study, and 39 had abnormal cytogenetics. One hundred percent of patients in this study had a partial or greater response, and 66% had a very good partial response or complete response. Seventy-nine percent of patients with adverse cytogenetics had a very good partial response or better. Fifteen patients proceeded to transplantation following successful completion of stem cells collection. This regimen appears to be very active in producing remissions in patients prior to autologous stem cell transplantation.

Revlimid, Velcade, Cytoxan, and Dexamethasone for Induction

Researchers involved in a U.S. multi-center trial reported that the combination of Velcade® (bortezomib), dexamethasone, Cytoxan, and Revlimid for initial treatment of patients with myeloma was well tolerated and produced a high response rate.[iv] Preliminary data showed that 100% of patients achieved a partial response or better, with approximately 50% achieving a complete response. These authors suggest that this regimen is tolerable and highly active in newly diagnosed patients with myeloma.

Revlimid for Consolidation/Maintenance

Italian researchers presented the results of a study where Revlimid was administered as consolidation/maintenance therapy after a reduced-intensity autologous stem cell transplants in elderly patients with newly diagnosed myeloma.[v] This study included over 100 patients aged 65-75 years with newly diagnosed myeloma. All received induction therapy with Velcade, dexamethasone, and doxorubicin followed by tandem autologous stem cell transplants with 100 mg/m2 of melphalan. Peripheral blood stem cells were harvested after Cytoxan and Neupogen® (figrastim). Revlimid was given after recovery from tandem autologous transplants. After consolidation/maintenance Revlimid, 88% of patients achieved at least a very good partial remission, and 53% a complete remission. One-year survival was 92%.