Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment for Multiple Myeloma
The VAD regimen has shown activity in previously treated and in untreated patients with response rates ranging from 60% to 80%.[47,48,49,50][Level of evidence: 3iiiDiv]
- No randomized studies support the widespread use of this regimen in untreated patients.
- This regimen avoids early exposure to alkylating agents, thereby minimizing any problems with stem cell collection (if needed) and any future risks for myelodysplasia or secondary leukemia.
- Disadvantages include the logistics for a 96-hour infusion of doxorubicin and a low complete response rate.
- An alternative version of VAD substitutes pegylated liposomal doxorubicin for doxorubicin, eliminates the need for an infusion, and provides comparable response rates.[51,52][Level of evidence: 3iiiDiv]
Evidence is not strong that any alkylating agent is superior to any other. All standard doses and schedules produce equivalent results. The two most common regimens historically have been oral MP and oral cyclophosphamide plus prednisone.[53,54,55]
Combinations, such as those used in EST-2479, of alkylating agents and prednisone, administered simultaneously or alternately, have not proven to be superior to therapy with MP.[56,57,58,59][Level of evidence: 1iiA]
A meta-analysis of studies comparing MP with drug combinations concluded that both forms of treatment were equally effective.[Level of evidence: 1iiA] Patients who relapsed after initial therapy with cyclophosphamide and prednisone had no difference in OS (median OS, 17 months) when randomly assigned to receive vincristine plus carmustine plus melphalan plus cyclophosphamide plus prednisone or VAD.[Level of evidence: 1iiA]
Several national and international trials have been implemented to define the optimal combination regimens. Participation in these trials should be the preferred approach, when feasible. The combination regimens in these trials represent the most successful from numerous phase II reports during the last several years.
- ECOG-E1A05: Bortezomib + dexamethasone versus lenalidomide + bortezomib + dexamethasone.
- SWOG-S0777: Lenalidomide + dexamethasone versus lenalidomide + bortezomib + dexamethasone.
- EVOLUTION (NCT00507442) trial: Bortezomib + lenalidomide + dexamethasone versus bortezomib + cyclophosphamide + dexamethasone versus bortezomib + lenalidomide + cyclophosphamide + dexamethasone.
- U.S. Intergroup/Intergroupe Francais du Myélome trial (IFM): Lenalidomide + bortezomib + dexamethasone for three cycles; responders are then randomly assigned to five more cycles of lenalidomide + bortezomib + dexamethasone or high-dose melphalan + stem cell transplantation.
- ECOG-E1A06: Thalidomide + melphalan + prednisone versus lenalidomide + melphalan + prednisone.
Options for combination regimens:
- Bortezomib + dexamethasone (as demonstrated in ECOG-E1A05).[39,61]
- Lenalidomide + dexamethasone (as demonstrated in SWOG-S0777).[5,30,31]
- Bortezomib + lenalidomide + dexamethasone (as demonstrated in ECOG-E1A05, SWOG-S0777, EVOLUTION trial, and the U.S. Intergroup/IFM trial).[39,61,62]
- Bortezomib + cyclophosphamide + dexamethasone (as demonstrated in the EVOLUTION trial).[63,64]
- Bortezomib + lenalidomide + cyclophosphamide + dexamethasone (as demonstrated in the EVOLUTION trial).
- Lenalidomide + cyclophosphamide + dexamethasone.
- Bortezomib + melphalan + prednisone.
- Bortezomib + liposomal doxorubicin +/- dexamethasone.[38,67]
- Melphalan + prednisone + thalidomide.[18,25]
- Melphalan + prednisone.[18,25]