Dr. Jewell is a hematology/oncology fellow, Dr. Xiang, Dr. Kunthur, and Dr. Mehta are staff hematologist/oncologists, all in the Division of Hematology/Oncology, Department of Internal Medicine, at the John L. McClellan Memorial Veterans Hospital in Little Rock, Arkansas. Dr. Xiang and Dr. Mehta are also faculty members at the University of Arkansas for Medical Sciences in Little Rock.
References
therefore, it is important to collect stem cells in transplanteligible patients who are aged < 65 years or for those who have received more than 4 cycles of treatment with this regimen. 23,24 A major AE to lenalidomidecontaining regimens is the increased risk of thrombosis. All patients on lenalidomide require treatment with aspirin at a minimum; however, those at higher risk for thrombosis may require low-molecular weight heparin or warfarin. 25
Carfilzomib Plus Lenalidomide Plus Dexamethasone
Carfilzomib is a recently approved PI that has shown promise in combination with lenalidomide and dexamethasone as initial therapy for MM. Several phase 2 trials have reported favorable results with carfilzomib in combination with lenalidomide and dexamethasone in MM. 26,27 More studies are needed to establish efficacy and safety before this regimen is routinely used as upfront therapy. 11
Thalidomide Plus Dexamethasone
Although there are no randomized controlled trials comparing lenalidomide plus dexamethasone with thalidomide plus dexamethasone, these regimens have been compared in retrospective studies. In these studies, lenalidomide plus dexamethasone showed both a higher response rate as well as an increased PFS and OS compared with thalidomide plus dexamethasone. Additionally, lenalidomide’s AE profile was more favorable than that of thalidomide. In light of this, lenalidomide plus dexamethasone is preferred to thalidomide plus dexamethasone in the management of MM, although the latter can be considered when lenalidomide is not available or when a patient does not tolerate lenalidomide. 28
VDT-PACE
A multidrug combination that should be considered in select populations is the VDT-PACE regimen, which includes bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide. This regimen can be considered in those patients who have aggressive disease, such as those with plasma cell leukemia or with multiple extramedullary plasmacytomas. 11
Autologous Stem Cell Transplant
Previous data suggest that ASCT improves OS in MM by 12 months. 29 A more recent open-label, randomized trial comparing melphalan and ASCT to melphalanprednisone-lenalidomide showed significant prolonged PFS and OS among patients with MM. 30 Although the role of ASCT may change as new drugs are integrated into initial therapy of MM, ASCT is still the preferred approach in transplant-eligible patients. As such, all patients who are eligible should be considered to receive a transplant.
There remains debate about whether ASCT should be performed early, after 2 to 4 cycles of induction therapy, or late after first relapse. Several randomized trials failed to show a difference in survival for early vs delayed ASCT approach. 31 Generally, transplant can be delayed for patients with standard-risk MM who have responded well to therapy. 11 Those patients who do not achieve a CR with their first ASCT may benefit from a second (tandem) ASCT. 32 An allogeneic transplant is occasionally used in select populations and is the only potentially
