The Evolving Treatment Landscape for the Elderly Multiple Myeloma Patient: From Quad Regimens to T-Cell Engagers and CAR-T
Simple Summary
Abstract
1. Introduction
2. General Considerations in the Treatment of Elderly Myeloma Patients
3. Triplet and Quadruplet Therapy
4. Immunotherapies
4.1. B-Cell Maturation Antigen
4.2. G-Protein Coupled Receptor, Family C, Group 5, Member D
5. T-Cell Engagers
5.1. T-Cell Engager Design
5.2. FDA-Approved Bispecific Antibodies
Agent | Sample Size, n= | Median Age Age ≥ 75 Years | HRCA *, % | Median No. Prior Lines | ORR | CR | MRD-Negativity (10−5) + | Median Follow-Up (Months) | Median Overall Survival (Months) | Median Progression-Free Survival (Months) | Treatment Discontinuation Due to AEs, % | CRS/ICANS All Grades/Grade ≥ 3 | Infections, % All Grades/Grade ≥ 3 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Teclistamab [65,70] | 165 | 64 15% | 26 | 5 | 63 | 46 | 29 | 30 | 22 | 11 | 5 | CRS: 72/1 ICANS: 3/0 | 79/55 |
Elranatamab [64,71] | 123 | 68 19% | 25 | 5 | 61 | 35 | 24 | 28 | 25 | 17 | 14 | CRS: 56/0 ICANS: 4/0 | 70/40 |
Talquetamab * [56,58] | 232 | 65 23% | 16 | 6 | 69 | 40 | NA | 19 | Not reached | 11 | 9 | CRS: 80/0 ICANS: 1/0 | 76/20 |
Cilta-cel [72,73] | 97 (113) † | 61 8% | 24 | 6 | 97 | 67 | 55 | 61 | 61 | 35 | - | CRS: 95/4 ICANS: 17/2 | 58/20 |
Ide-cel [74] ^ | 128 (140) † | 61 8% | 35 | 6 | 81 | 39 | 26 | 13 | 19 | 12 | - | CRS: 84/5 Neurotoxicity ‡: 18/3 | 70/NA |
5.3. Trispecific-Antibodies
6. CAR-T Therapy
6.1. CAR-T Design and Production
6.2. FDA-Approved CAR-T
7. Strengths and Weaknesses of T-Cell Redirecting Therapies
8. Moving Immunotherapy into the Front Line
9. Future Directions
10. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Trial, Treatment Combination | Sample Size, n= | Median Age Age ≥ 75 Years | HRCA *, % | ISS = III, % | ORR | CR | MRD-Negativity (10−5) | Median Follow-Up (Months) | Median Overall Survival (Months) | Median Progression-Free Survival (Months) | Treatment Discontinuation Due to AEs, % | Peripheral Neuropathy, % All Grades/Grade ≥ 3 | Infections, % All Grades/Grade ≥ 3 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
MAIA † [7,34] Rd | 369 | 74 44% | 14 | 30 | 81 | 30 | 11 | 65 | 66 | 34 | 22 | 18/1 | NA/29 |
MAIA † [7,34] DRd | 368 | 73 43% | 15 | 29 | 93 | 51 | 32 | 65 | Not reached | 62 | 13 | 28/2 | NA/41 |
ALCYONE ± [32,33] VMP | 356 | 71 30% | 15 | 36 | 74 | 24 | 6 | 40 | Not reached | 19 | 9 | 32/4 | 48/15 |
ALCYONE ± [32,33] D-VMP | 350 | 71 30% | 17 | 41 | 91 | 43 | 22 | 40 | Not reached | 36 | 7 | 28/1 | 67/23 |
SWOG777 ‡ [35,36] Rd | 225 | 63 NA | NA | 35 | 79 | 12 | NR | 84 | 56 (>65 years) | 24 (>65 years) | 10 | NA | 31/16 |
SWOG777 ‡ [35,36] VRd | 235 | 63 NA | NA | 33 | 90 | 24 | NR | 84 | 65 (>65 years) | 34 (>65 years) | 23 | NA | 33/18 |
CEPHEUS¶ [37] VRd | 195 | 70 NA | 14 | 28 | 93 | 62 | 39 | 59 | Not reached | 53 | 16 | 61/8 | 86/32 |
CEPHEUS¶ [37] D-VRd | 197 | 70 NA | 13 | 28 | 97 | 81 | 61 | 59 | Not reached | Not reached | 8 | 56/8 | 92/40 |
IMROZ ^ [38] VRd | 181 | 72 32% | 19 | NR R-ISS: 11 | 92 | 64 | 58 | 60 | Not reached | 45 | 26 | 61/6 | 87/38 |
IMROZ ^ [38] Isa-VRd | 265 | 72 26% | 15 | NR R-ISS: 12 | 91 | 75 | 44 | 60 | Not reached | Not reached | 23 | 54/7 | 91/45 |
BENEFIT + [39] Isa-Rd | 135 | 74 36% | NA | 20 | 78 | 31 | 26 | 24 | Not reached | Not reached | 3 | 28/1 | 39/NA |
BENEFIT + [39] Isa-VRd | 135 | 73 31% | NA | 16 | 85 | 58 | 53 | 24 | Not reached | Not reached | 4 | 52/3 | 47/NA |
Characteristic | CAR-T | T-Cell Engagers |
---|---|---|
FDA-approved agents | Ide-cel Cilta-cel | Teclistamab Elranatamab Talquetamab |
Manufacturing time/availability | 4–8 weeks | ‘Off-the-shelf’ Immediate |
Treatment frequency | ‘One-and-done’, Once off therapy | Ongoing Q1–2 Weekly |
Hospitalization required | Yes | Cycle 1 or not at all |
Specialized requirements | Foundation for the accreditation of Cellular Therapy (FACT) or Joint Accreditation Committee ISCT-Europe & EBMT (JACIE) | Risk Evaluation and Mitigation Strategy (REMS) program |
Cytokine release syndrome All grades /≥ Grade3 | 85–95/5 | 60–70/0–1 |
ICANS, % All grades/ ≥ Grade3 | 15/2 | 3–4/0 |
Infections, % All grades/ ≥ Grade3 | 58/20 | BCMA: 70–75/40–45 GPRC5D: 76/20 |
Hypogammaglobulinemia, % | 90 | 75–95 |
Overall response rate, % | 75–95 | 60–70 |
Median progression-free survival in late relapse (>3 prior lines) | 12–35 months | 11–17 months |
Expense | $$$ | $$ |
Future directions | Maintenance strategies Streamlined manufacturing, reduce vein-to-vein time Improved bridging strategies Enhanced CAR-T design: armored CARs, dual antigen binding, etc. | Combination therapy Time-limited therapy Reduced intensity schedules Outpatient administration |
Trial, Treatment Combination | Sample Size | Population | Phase | Combination Therapies | Comparator Arm |
---|---|---|---|---|---|
CARTITUDE-5 [116] | Target n = 650 | Transplant-ineligible or transplant not planned | 3 | Cilta-cel + Bortezomib Lenalidomide Dexamethasone | Bortezomib Lenalidomide Dexamethasone |
MAJESTEC-7 [117] | Target n = 1000 | Transplant-ineligible | 3 | Teclistamab + Daratumumab Lenalidomide Dexamethasone | Daratumumab Lenalidomide Dexamethasone |
MAGNESTISMM-6 [118] | Target n = 646 | Transplant-ineligible | 3 | Elranatamab + Daratumumab Lenalidomide Dexamethasone | Daratumumab Lenalidomide Dexamethasone |
Linvoseltamab NCT06932562 | Target n = 1000 | Transplant-ineligible | 3 | Linvoseltamab + Daratumumab Lenalidomide Dexamethasone | Daratumumab Lenalidomide Dexamethasone |
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Rees, M.J.; Quach, H. The Evolving Treatment Landscape for the Elderly Multiple Myeloma Patient: From Quad Regimens to T-Cell Engagers and CAR-T. Cancers 2025, 17, 2579. https://doi.org/10.3390/cancers17152579
Rees MJ, Quach H. The Evolving Treatment Landscape for the Elderly Multiple Myeloma Patient: From Quad Regimens to T-Cell Engagers and CAR-T. Cancers. 2025; 17(15):2579. https://doi.org/10.3390/cancers17152579
Chicago/Turabian StyleRees, Matthew James, and Hang Quach. 2025. "The Evolving Treatment Landscape for the Elderly Multiple Myeloma Patient: From Quad Regimens to T-Cell Engagers and CAR-T" Cancers 17, no. 15: 2579. https://doi.org/10.3390/cancers17152579
APA StyleRees, M. J., & Quach, H. (2025). The Evolving Treatment Landscape for the Elderly Multiple Myeloma Patient: From Quad Regimens to T-Cell Engagers and CAR-T. Cancers, 17(15), 2579. https://doi.org/10.3390/cancers17152579