Treatment for Multiple Myeloma
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.[51,52,53,54][Level of evidence: 1iiA]
A meta-analysis of studies comparing melphalan plus prednisone 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 mo) when randomly assigned to receive vincristine plus carmustine plus melphalan plus cyclophosphamide plus prednisone or VAD.
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-SO777: Lenalidomide + dexamethasone versus lenalidomide + bortezomib + dexamethasone.
- EVOLUTION trial: Bortezomib + lenalidomide + dexamethasone versus bortezomib + cyclophosphamide + dexamethasone versus bortezomib + lenalidomide + cyclophosphamide + dexamethasone.
- U.S. Intergroup/IFM trial: 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.
Options for combination regimens:
- Bortezomib + dexamethasone (as demonstrated in ECOG-E1A05).[38,56]
- Lenalidomide + dexamethasone (as demonstrated in SWOG-SO777).[5,32,33]
- Bortezomib + lenalidomide + dexamethasone (as demonstrated in ECOG-E1A05, SWOG-SO777, EVOLUTION trial, and U.S. Intergroup/IFM trial).[38,56,57]
- Bortezomib + cyclophosphamide + dexamethasone (as demonstrated in the EVOLUTION trial).[58,59]
- Bortezomib + lenalidomide + cyclophosphamide + dexamethasone (as demonstrated in the EVOLUTION trial).
- Lenalidomide + cyclophosphamide + dexamethasone.
- Bortezomib + melphalan + prednisone.
- Bortezomib + liposomal doxorubicin.
- Melphalan + prednisone + thalidomide.[18,25]
- Melphalan + prednisone.[18,25]
High-dose chemotherapy: Autologous bone marrow or peripheral stem cell transplantation
The failure of conventional therapy to cure the disease has led investigators to test the effectiveness of much higher doses of drugs such as melphalan. The development of techniques for harvesting hemopoietic stem cells, from marrow aspirates or the peripheral blood of the patient, and infusing these cells to promote hemopoietic recovery made it possible for investigators to test very large doses of chemotherapy.
Based on the experience of treating thousands of patients in this way, it is possible to draw a few conclusions, including the following:
- The risk of early death caused by treatment-related toxic effects has been reduced to less than 3% in highly selected populations.
- Chemotherapy patients can now be treated as outpatients.
- Extensive prior chemotherapy, especially with alkylating agents, compromises marrow hemopoiesis and may make the harvesting of adequate numbers of hemopoietic stem cells impossible.
- Younger patients in good health tolerate high-dose therapy better than patients with a poor performance status.[63,64,65]