The Role of Autologous Stem Cell Transplantation in the Treatment of Newly Diagnosed Multiple Myeloma: Is It Time to Rethink the Paradigm in the Era of Targeted Therapy?
Abstract
:1. Introduction
2. The Benefits of HDM
3. The Downsides of HDM
4. One Size Does Not Fit All—Personalized Treatment Decision Making
4.1. Patient and Disease Heterogeneity
4.2. MRD Evaluation for Adaptive Therapy
5. Alternatives to HDM-ASCT and the Emerging Role of Quadruplet Therapy
6. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study | Induction Therapy | ASCT | Consolidation Therapy | Maintenance Therapy | MRD-Negativity Rate |
---|---|---|---|---|---|
IFM 2009 [8,11] | RVd × 3 3-week cycles | No | RVd × 5 3-week cycles | R, 1 year | 20% |
IFM 2009 [8,11] | RVd × 3 3-week cycles | Yes | RVd × 2 3-week cycles | R, 1 year | 30% |
GRIFFIN [12,29] | RVd × 4 3-week cycles | Yes | RVd × 2 3-week cycles | R | 30% |
DSMM XVII [24] | KRd × 6 4-week cycles | Yes | KRd × 4 4-week cycles | R | 35% post induction |
GMMG-HD7 [22] | RVd × 3 6-week cycles | No | – | R + Isa vs. R | 36% post induction |
DETERMINATION [3] | RVd × 3 3-week cycles | No | RVd × 5 3-week cycles | R until progression | 40% * |
FORTE [9] | KCd × 4 4-week cycles | Yes | KCd × 4 4-week cycles | KR vs. R | 43% |
CASSIOPEIA [10] | VTd × 4 4-week cycles | Yes | VTd × 2 4-week cycles | Dara vs. observation | 44% |
PERSEUS [27] | RVd × 4 4-week cycles | Yes | RVd × 2 4-week cycles | R until progression | 48% |
GEM2012MENOS65 [14] | RVd × 6 3-week cycles | Yes | RVd × 2 3-week cycles | IRd or Rd | 49% (SR); 37% (HR) |
DETERMINATION [3] | RVd × 3 3-week cycles | Yes | RVd × 2 3-week cycles | R until progression | 54% * |
FORTE [9] | KRd × 12 4-week cycles | No | – | KR vs. R | 56% |
FORTE [9] | KRd × 4 4-week cycles | Yes | KRd × 4 4-week cycles | KR vs. R | 62% |
Myeloma XI [13] | CTD/CRD/KCRD × 4 cycles | Yes | – | R vs. none | 63% (3 months post-ASCT) |
IsKia [21] | KRd × 4 4-week cycles | Yes | KRd × 4, KRd-light × 12 | R | 67% post consolidation |
CASSIOPEIA [10] | Dara-VTd × 4 4-week cycles | Yes | VTd × 2 4-week cycles | Dara vs. observation | 44% |
DSMM XVII [24] | Elo-KRd × 6 4-week cycles | Yes | Elo-KRd × 4 4-week cycles | Elo-R | 50% post induction |
GMMG-HD7 [22] | Isa-RVd × 3 6-week cycles | No | – | R + Isa vs. R | 50% post induction |
IFM 2018-01 [30] | Dara-IRd × 6 3-week cycles | Yes | Dara-IRd × 4 4-week cycles | R, 2 years | 51% (SR, after 1 year of maintenance) |
NCT04113018 [16] | Dara-KRd × 8 4-week cycles | No/Yes/No | –/Dara-KRd × 12 4-week cycles/Dara-KRd × 12 4-week cycles | R | 62% post induction |
Derman et al. [19] | Dara-KRd × 24 4-week cycles | No | – | – | 63% (post 8 cycles) |
GRIFFIN [12,29] | Dara-RVd × 4 3-week cycles | Yes | Dara-RVd × 2 3-week cycles | Dara-R | 64% |
SKylaRk [26] | Isa-KRd × 4 4-week cycles | Yes/No | Isa-KRd × 2/4 4-week cycles | Isa-KR (HR), R (SR) | 66% (post 6 cycles) |
GMMG-CONCEPT [25] | Isa-KRd × 6 4-week cycles | Yes/No | Isa-KRd × 4 4-week cycles | Isa-KR, 26 cycles | 68%/54% |
IRB16-1138 [20] | Elo-KRd × 12 4-week cycles | No | Elo-KRd × 0–12 4-week cycles | Elo-Rd | 70% |
MANHATTAN [31] | Dara-KRd × 8 4-week cycles | No | – | – | 71% |
PERSEUS [27] | Dara-RVd × 4 4-week cycles | Yes | Dara-RVd × 2 4-week cycles | Dara-R/R until progression | 75% |
IsKia [21] | Isa-KRd × 4 4-week cycles | Yes | Isa-KRd × 4, Isa-KRd-light × 12 | R | 77% post consolidation |
MASTER [17,18] | Dara-KRd × 4 4-week cycles | Yes | Dara-KRd × 0–8 4-week cycles | R | 38% (post induction) 81% (post MRD-directed consolidation) |
IFM2018-04 [28] | Dara-KRd × 6 4-week cycles | Yes | Dara-KRd × 4 4-week cycles | Dara-R, 2 years | 94% |
OPTIMUM/MUKnine (UHR NDMM) [23] | Dara-CRVd × 6 cycles | Yes | Dara-RVd × 6 cycles, Dara-RV × 12 cycles | Dara-R until progression | 64% post ASCT |
Agent | Study | Phase | ClinicalTrials.gov ID | Setting | Primary Endpoint | Initial Completion Date |
---|---|---|---|---|---|---|
CAR T cell therapies | ||||||
Ide-cel | KarMMa-2 [74] | 2 | NCT03601078 | Inadequate response to ASCT in 1st line | ORR CR rate | July 2025 |
KarMMa-9 | 3 | NCT06045806 | Ide-cel + R vs. R maintenance for sub-optimal response post ASCT | PFS | March 2031 | |
BMTCTN1902 | 2 | NCT05032820 | Sub-optimal response post ASCT and R maintenance | sCR/CR rate at 6 months | January 2025 | |
Cilta-cel | CARTITUDE-6 [75] | 3 | NCT05257083 |
| PFS Sustained MRD-neg CR | June 2033 |
CARTITUDE-2 | 2 | NCT04133636 |
| MRD-neg | May 2025 | |
CARTITUDE-5 | 3 | NCT04923893 |
| PFS | June 2026 | |
Antibody–drug conjugates | ||||||
Belantamab mafodotin | GEM-BELA-RVd | 2 | NCT04802356 |
| Safety, AEs | July 2025 |
LCI-HEM-NDMYE-KRDB-001 | 1/2 | NCT04822337 |
| CR rate | October 2024 | |
Winship5382-21 | 2 | NCT05208307 | Belantamab mafodotin plus Pom-dex as post-ASCT maintenance in high-risk patients | CR rate | October 2024 | |
I 797720 | 2 | NCT04876248 | Belantamab mafodotin plus R as post-ASCT maintenance in MRD-pos patients | MRD-neg rate | September 2026 | |
MDACC 2021-0201 | 2 | NCT05091372 | Belantamab mafodotin plus R as MRD-guided post-ASCT maintenance | MRD-pos to MRD-neg rate | March 2025 | |
UPCC 37420 | 2 | NCT04680468 | Belantamab mafodotin prior to ASCT and with R as maintenance | MRD-neg rate | July 2026 | |
DREAMM-9 | 1 | NCT04091126 | Belantamab mafodotin + RVd or Rd, nontransplant setting | Safety, AEs | April 2025 | |
MC1989 | 1/2 | NCT04892264 | Belantamab mafodotin + Dara-Rd, nontransplant setting | CR rate | March 2025 | |
EAE120 | 1/2 | NCT05280275 | Belantamab mafodotin + Dara-Rd, nontransplant setting | Safety, AEs ORR | March 2026 | |
EAE128 | 1/2 | NCT05573802 | Belantamab mafodotin + Rd + nirogacestat, nontransplant setting | Safety, DLTs, AEs ORR | October 2026 | |
EAE-2020 | 1/2 | NCT04808037 | Belantamab mafodotin + Rd, nontransplant setting | Safety, AEs ORR | September 2028 | |
Bispecific antibodies/T cell engagers | ||||||
Teclistamab (BCMA × CD3) | MASTER-2 | 2 | NCT05231629 |
| Sustained MRD-neg rate | December 2026 |
IFM 2021-01 | 2 | NCT05572229 |
| VGPR rate | May 2025 | |
MajesTEC-2 | 1 | NCT04722146 |
| Safety, DLTs | October 2024 | |
MajesTEC-4 [76] | 3 | NCT05243797 | Teclistamab-R vs. R as post-ASCT maintenance | PFS | April 2028 | |
MajesTEC-5/GMMG-HD10 | 2 | NCT05695508 |
| Safety | October 2026 | |
MajesTEC-7 [77] | 3 | NCT05552222 |
| PFS MRD-neg CR | May 2029 | |
GEM-TECTAL | 2 | NCT05849610 |
| MRD-neg CR | January 2025 | |
Elranatamab (BCMA × CD3) | MagnetisMM-7 [78] | 3 | NCT05317416 |
| PFS | August 2027 |
MagnetisMM-6 [79] | 3 | NCT05623020 |
| PFS MRD-neg rate | March 2028 | |
NCI-2024-00110 | 2 | NCT06207799 | Pre-ASCT purging/post-ASCT maintenance | Safety | December 2029 | |
Talquetamab (GPRC5D × CD3) | MonumenTAL-2 | 1 | NCT05050097 |
| Safety DLTs | December 2024 |
Cevostamab (FcRH5 × CD3) | PLYCOM | 1/2 | NCT05583617 |
| Safety, Response rates PFS, OS | March 2026 |
CELMoDs | ||||||
Iberdomide | MIDAS IFM 2020-02 | 3 | NCT04934475 | Iberdomide + Isa vs. R + Isa as post-ASCT maintenance | MRD-neg rate | December 2024 |
EXCALIBER-Maintenance | 3 | NCT05827016 | Iberdomide vs. R maintenance post ASCT | PFS | March 2029 | |
GMMG-HD9/DSMM XVIII | 3 | NCT06216158 | Iberdomide + Isa vs. iberdomide maintenance post ASCT | 2-year MRD-neg rate | December 2028 | |
GEM21menos65 | 3 | NCT05558319 | Iberdomide + Isa-Vd vs. RVd vs. Isa-RVd | MRD-neg rate | April 2027 | |
CC-220-MM-001 | 1/2 | NCT02773030 |
| Safety ORR | July 2026 | |
BOREALIS | 2 | NCT05272826 |
| sCR rate | March 2028 | |
EMN26 [80] | 2 | NCT04564703 |
| Improved efficacy Tolerability | December 2027 | |
IBEX | 2 | NCT06107738 | Iberdomide + SC Dara as post-ASCT maintenance | 12-month MRD-neg rate | December 2025 | |
KID | 1/2 | NCT05199311 |
| AEs CR/sCR rate | November 2025 | |
MSKCC 22-040 | 2 | NCT05354557 |
| CR rate | April 2025 | |
University of Nebraska 852-21 | 2 | NCT05177536 |
| 1-year tolerability | March 2025 | |
IDEAL | 1/2 | NCT05392946 |
| MTD CR rate | May 2027 | |
COMMANDER | 1b/2 | NCT05434689 |
| DLT MRD conversion rate | December 2025 | |
GEM-IBERDARAX | 2 | NCT05527340 |
| ORR CR rate | December 2029 |
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Richardson, P.G. The Role of Autologous Stem Cell Transplantation in the Treatment of Newly Diagnosed Multiple Myeloma: Is It Time to Rethink the Paradigm in the Era of Targeted Therapy? Hemato 2024, 5, 144-156. https://doi.org/10.3390/hemato5020012
Richardson PG. The Role of Autologous Stem Cell Transplantation in the Treatment of Newly Diagnosed Multiple Myeloma: Is It Time to Rethink the Paradigm in the Era of Targeted Therapy? Hemato. 2024; 5(2):144-156. https://doi.org/10.3390/hemato5020012
Chicago/Turabian StyleRichardson, Paul G. 2024. "The Role of Autologous Stem Cell Transplantation in the Treatment of Newly Diagnosed Multiple Myeloma: Is It Time to Rethink the Paradigm in the Era of Targeted Therapy?" Hemato 5, no. 2: 144-156. https://doi.org/10.3390/hemato5020012