Results of selected randomized trials that have had a major impact on myeloma therapy
| Trial, treatment comparison . | Total no. of patients studied . | CR/VGPR, % . | Median PFS, mo . | Median OS, mo . | Comments . |
|---|---|---|---|---|---|
| Stem-cell transplantation | |||||
| IFM 90*77 | |||||
| Conventional chemotherapy | 100 | 13 | 18 | 44 | Established role of ASCT |
| ASCT | 100 | 38 | 28 | 57 | — |
| MRC VII*78 | |||||
| Conventional chemotherapy | 201 | 8 | 20 | 42 | Confirmed role of ASCT |
| ASCT | 200 | 44 | 32 | 54 | — |
| MAG 90*79 | |||||
| Delayed ASCT | 94 | 21 | 13 | 65 | Demonstrated delayed ASCT as an alternative |
| Early ASCT | 91 | 32 | 39 | 64 | — |
| United States Intergroup S9321*80 | |||||
| Delayed ASCT | 255 | 15§ | 21 | 64 | Demonstrated delayed ASCT as an alternative; dampened enthusiasm for allogeneic SCT |
| Early ASCT | 261 | 17§ | 25 | 58 | — |
| Allogeneic SCT | 36 | 17§ | NR | 6 | — |
| IFM 94*81 | |||||
| Single ASCT | 199 | 42 | 25 | 48 | Established role of tandem ASCT if CR/VGPR not achieved with first ASCT |
| Double ASCT | 200 | 50 | 30 | 58 | — |
| PETHEMA†82 | |||||
| Conventional chemotherapy | 83 | 11§ | 33 | 66 | Demonstrated that ASCT may have limited value in patients responding well to induction |
| ASCT | 81 | 30§ | 42 | 61 | — |
| Italian*83 | |||||
| Tandem ASCT | 82 | NA | 29 | 54 | Demonstrated efficacy of single ASCT followed by nonmyeloablative SCT in selected patients |
| Single ASCT followed by nonmyeloablative SCT | 80 | NA | 35 | 80 | — |
| New therapies | |||||
| Italian GIMEMA group*84 | |||||
| MP | 126 | 12 | 27 | 64% at 3 y | Demonstrated potential value of MPT over the classic MP regimen |
| MPT | 129 | 36 | 54 | 80% at 3 y | — |
| IFM 99-06*85 | |||||
| MP | 196 | 7 | 18 | 33 | Changed standard of care in elderly to MPT (after 3 decades of MP) |
| MPT | 125 | 47 | 28 | 52 | — |
| Tandem intermediate-dose ASCT | 126 | 43 | 19 | 38 | — |
| APEX‡52 | |||||
| Bortezomib | 333 | 13¶ | 6‖ | NR | Led to full approval of bortezomib in the United States |
| Dex | 336 | 2¶ | 3‖ | NR | — |
| MM-010‡72 | |||||
| Len/Dex | 176 | 24¶ | 11‖ | Not reached | Pivotal trial establishing role of Len |
| Placebo/Dex | 175 | 5¶ | 5‖ | 21 | — |
| MM-009‡73 | |||||
| Len/Dex | 177 | 24¶ | 11§ | 30 | Led to approval of Len in the United States |
| Placebo/Dex | 176 | 2¶ | 5§ | 20 | — |
| Trial, treatment comparison . | Total no. of patients studied . | CR/VGPR, % . | Median PFS, mo . | Median OS, mo . | Comments . |
|---|---|---|---|---|---|
| Stem-cell transplantation | |||||
| IFM 90*77 | |||||
| Conventional chemotherapy | 100 | 13 | 18 | 44 | Established role of ASCT |
| ASCT | 100 | 38 | 28 | 57 | — |
| MRC VII*78 | |||||
| Conventional chemotherapy | 201 | 8 | 20 | 42 | Confirmed role of ASCT |
| ASCT | 200 | 44 | 32 | 54 | — |
| MAG 90*79 | |||||
| Delayed ASCT | 94 | 21 | 13 | 65 | Demonstrated delayed ASCT as an alternative |
| Early ASCT | 91 | 32 | 39 | 64 | — |
| United States Intergroup S9321*80 | |||||
| Delayed ASCT | 255 | 15§ | 21 | 64 | Demonstrated delayed ASCT as an alternative; dampened enthusiasm for allogeneic SCT |
| Early ASCT | 261 | 17§ | 25 | 58 | — |
| Allogeneic SCT | 36 | 17§ | NR | 6 | — |
| IFM 94*81 | |||||
| Single ASCT | 199 | 42 | 25 | 48 | Established role of tandem ASCT if CR/VGPR not achieved with first ASCT |
| Double ASCT | 200 | 50 | 30 | 58 | — |
| PETHEMA†82 | |||||
| Conventional chemotherapy | 83 | 11§ | 33 | 66 | Demonstrated that ASCT may have limited value in patients responding well to induction |
| ASCT | 81 | 30§ | 42 | 61 | — |
| Italian*83 | |||||
| Tandem ASCT | 82 | NA | 29 | 54 | Demonstrated efficacy of single ASCT followed by nonmyeloablative SCT in selected patients |
| Single ASCT followed by nonmyeloablative SCT | 80 | NA | 35 | 80 | — |
| New therapies | |||||
| Italian GIMEMA group*84 | |||||
| MP | 126 | 12 | 27 | 64% at 3 y | Demonstrated potential value of MPT over the classic MP regimen |
| MPT | 129 | 36 | 54 | 80% at 3 y | — |
| IFM 99-06*85 | |||||
| MP | 196 | 7 | 18 | 33 | Changed standard of care in elderly to MPT (after 3 decades of MP) |
| MPT | 125 | 47 | 28 | 52 | — |
| Tandem intermediate-dose ASCT | 126 | 43 | 19 | 38 | — |
| APEX‡52 | |||||
| Bortezomib | 333 | 13¶ | 6‖ | NR | Led to full approval of bortezomib in the United States |
| Dex | 336 | 2¶ | 3‖ | NR | — |
| MM-010‡72 | |||||
| Len/Dex | 176 | 24¶ | 11‖ | Not reached | Pivotal trial establishing role of Len |
| Placebo/Dex | 175 | 5¶ | 5‖ | 21 | — |
| MM-009‡73 | |||||
| Len/Dex | 177 | 24¶ | 11§ | 30 | Led to approval of Len in the United States |
| Placebo/Dex | 176 | 2¶ | 5§ | 20 | — |
CR indicates complete response; VGPR, very good partial response; PFS, progression-free survival; OS, overall survival; IFM, InterGroupe Francophone du Myélome; MRC, Medical Research Council; MAG, Myélome Autogreffe; PETHEMA, Programa para el Estudio y Tratamiento de las Hemopatias Malignas; GIMEMA, Gruppo Italiano Malattie Ematologiche dell'Adulto; ASCT, autologous hematopoietic stem-cell transplantation; NA, not applicable; SCT, stem-cell transplantation; MP, melphalan plus prednisone; MPT, melphalan, prednisone, thalidomide; NR, not reported; Dex, dexamethasone; MM, multiple myeloma; and Len, lenalidomide.
Newly diagnosed disease stage.
Postinduction (responding patients only) disease stage.
Relapsed, refractory (1-3 prior therapies) disease stage.
CR only; VGPR not reported.
CR or near CR.
PFS data not available; numbers reflect median time to progression.