To the editor,
The therapeutic landscape of multiple myeloma (MM) continues to evolve at a fast pace, driven by scientific and engineering advances in immunotherapy. At the American Society of Hematology (ASH) 2025 meeting, multiple presentations generated high enthusiasm, highlighting how bispecific antibodies (BsAbs), minimal residual disease (MRD)-adaptive strategies, and next-generation immune platforms are redefining depth, durability, and sequencing of therapies across all MM stages. Here, we summarize highlights of select few MM abstracts, with relevant properties of therapeutic agents summarized in Table 1 and key results summarized in Table 2 .
Table 1
Key properties of novel immunotherapies and immunomodulator
| Agent | Class | Target | Mechanism of Action | Key Features | Ref |
| Linvoseltamab | BsAb | BCMA × CD3 | Binds CD3 on T cells and BCMA on myeloma cells → T-cell activation, cytokine release, myeloma cell lysis | IV administration, quickest time to CRS, lower CRS rate vs. other BsAbs | [ 1 ] |
| Teclistamab | Bispecific Antibody (BsAb) | BCMA × CD3 | Redirects T cells to BCMA-expressing myeloma cells, forming immune synapse → T-cell activation → tumor lysis | First BsAb ever approved, SC administration | [ 2 – 4 ] |
| Elranatamab | BsAb | BCMA × CD3 | T-cell redirection to BCMA+ myeloma cells → activation and tumor killing | SC administration, quickest SUD | [ 5 , 6 ] |
| Talquetamab | BsAb | GPRC5D × CD3 | Redirects T cells to GPRC5D-expressing myeloma cells → T-cell activation → tumor lysis | First and only GPRC5D BsAb; associated with skin/nail/taste changes | [ 7 , 8 ] |
| Iberdomide | Cereblon E3 Ligase Modulator | Cereblon | 20× higher cereblon affinity than IMiDs → enhanced Ikaros/Aiolos degradation → direct anti-myeloma + immunostimulatory effects; enhances T-cell fitness | Oral, synergy with BsAbs and anti-CD38 antibodies | [ 5 , 11 ] |
| KLN-1010 | In vivo CAR-T gene therapy | BCMA | IV-administered gene therapy generates anti-BCMA CAR-T cells in vivo | No required apheresis, lymphodepletion or bespoke manufacturing; off-the-shelf | [ 10 ] |
Table 2
Key multiple myeloma clinical trial result summary from ASH 2025 meeting
*MRD negativity in evaluable patients **Treatment-emergent adverse event according to the Medical Dictionary for Regulatory Activities v28.1 and Common Terminology Criteria for Adverse Events v5 (G= grade)
| Trial (ASH Abstract no.) | Population | Regimen | Response | MRD | Key Safety** | Clinical Implication |
| IMMUNOPLANT (248) | NDMM MRD+ post quadruplet therapy ( n = 19) | Linvoseltamab | 100% MRD + to MRD- conversion | 10⁻⁶: 100%* | Minimal CRS/ICANS | MRD-guided consolidation. Limitation: small sample, durability unknown |
| TecLille (367) | Elderly TIE NDMM ( n = 37) | Tec + Dara | ORR 100%; ≥VGPR 97% | 10 ⁻5 and 10⁻⁶: 100%* | G ≥ 3 infection 14%. No G5 AEs | Feasibility of frontline Ab/BsAb in frail populations |
| MajesTEC-3 (LBA6) | RRMM (1–3 LOT) ( n = 587) | Tec + Dara vs. DPd/DVd | ORR 89% ≥CR 82% 36-mo PFS 83.4% vs. 29.7% 36-mo OS 83.3% vs. 65% | 10⁻⁵: 58% | G ≥ 3 infections 54%; hypogamma-globulinemia 84.5% | Practice-transforming in early relapse. Limitations: infection risk; CD38-naïve predominance (95%) |
| MagnetisMM-30 (100) | RRMM (2–4 LOT) ( n = 22) | Elra + Iber | ORR 96%; CR ≥ 46% | - | G ≥ 3 neutropenia 73%, G ≥ 3 infection 9.1% | BsAb + CELMoD synergy Limitation: significant neutropenia |
| RedirecTT-1 (698) | RRMM + EMD ( n = 90) | Talq + Tec | ORR 79%; ≥ CR 53% Median DOR NR | - | Infection: 32% G ≥ 3, 12% G5. | Best signal in EMD. Limitation: infection, tolerability |
| inMMyCAR (LBA1) | RRMM, > 3 LOT ( n = 3) | KLN-1010 | 3/3 MRD negative by NGS or NGF | MRD negative by month 1 | CRS ≤G2: 2/3 No ICANS | Cutting-edge, proof-of-concept so far |
Bispecific antibodies redefine depth and durability
ASH 2025 marked an inflection point in the field for BsAb–based immunotherapy in newly diagnosed (NDMM) and early relapsed/refractory MM (RRMM). Post-induction MRD-adaptive immunotherapy emerged as a strategy to deepen responses. The phase II IMMUNOPLANT study demonstrated that abbreviated, fixed-duration linvoseltamab consolidation could convert persistent MRD positivity after quadruplet induction into deep MRD-negative remissions with minimal toxicity in all studied patients [ 1 ]. While follow-up remains short, an excellent safety profile supports a paradigm in which MRD status informs appropriate therapeutic intensification, facilitating deeper remissions with BsAb without prolonged exposure to other therapies.
Frontline data reinforced the expanding role of BsAbs. In the IFM2021-01 TecLille study, Tec-Dara achieved exceptionally deep responses in elderly, transplant-ineligible patients with NDMM. These results raise the possibility that antibody-only immunotherapy may serve as a powerful alternative to cytotoxic regimens in frail populations. Notably, relatively low (14%) incidence of severe infections was observed with routine immunoglobulin replacement [ 2 ], suggesting that SOC infection prevention strategies are effective and integral to the safe delivery of these regimens.
The phase III MajesTEC-3 trial demonstrated significant improvements in both progression-free survival (PFS) and overall survival (OS) with teclistamab (Tec) plus daratumumab (Dara) compared with standard triplet regimens in RRMM. The overall response rate (ORR) in Tec-Dara arm was striking, comparable to CAR-T therapy [ 3 , 4 ], suggesting that this combination could fundamentally alter our treatment and long-term outcomes expectations. It is important to note that most patients (95%) were anti-CD38 antibody–naïve and infectious complications were common, underscoring the importance of patient selection, and preemptive standard of care (SOC) supportive care.
Next-generation immune strategies-combination, consolidation, and engineering
The phase 1b MagnetisMM-30 trial explored the combination of elranatamab with the iberdomide, cereblon E3 ligase modulator, leveraging immune interplay to enhance T-cell fitness and reduce T-cell exhaustion. Deep responses were observed despite heavily pretreated patients [ 5 , 6 ], supporting the biological rationale of this approach. Frequent neutropenia and infectious complications have led to further refinement of dosing and scheduling of this powerful combination which will be explored in the part 2 dose optimization effort, in order to prepare this combination for potential broader investigation and adoption.
ASH 2025 also highlighted the combination of immune approaches to address biologically aggressive subsets, including those with extramedullary disease (EMD). Extended follow-up from the RedirecTT-1 study demonstrated that dual BsAb targeting with talquetamab (tal) and tec at flexible dosing schedules produced superior efficacy with manageable safety profiles in RRMM with EMD [ 7 , 8 ], a high unmet need population historically associated with dismal outcomes [ 9 ]. The observed depth of response supports the approach of dual-BsAb engagement which may further mitigate spatial heterogeneity and antigen escape. However, the incidence of infections was common, including infection-related grade 5 events, highlighting the need for continued dose optimization and vigilant supportive care.
Perhaps, the most conceptually provocative data at meeting emerged from the first-in-human inMMyCAR study evaluating in-vivo generation of anti-BCMA CAR T cells. Despite the very small cohort of 3 patients, rapid responses and early MRD negativity at 1 month to this off-the-shelf therapy showed the transformative potential of eliminating delays related to apheresis, bespoke manufacturing, and lymphodepletion [ 10 ]. With the limited sample size and short follow-up, long-term biologic uncertainties related to safety and durability remain unknown.
Together, these studies signal a shift in therapeutic MM approach toward earlier, deeper, and more adaptive immune-based approaches, with BsAbs now rivaling cellular therapies in efficacy across all disease stages. As these insights move closer to frontline realities, access to therapy, durability and depth of response will need to be balanced with careful mitigation of infection risks and cumulative immune and pharmacoeconomic toxicity.
Acknowledgements
Not applicable.
Abbreviations
American Society of Hematology
Line of therapy
Minimal residual disease
B-cell maturation antigen
G protein—coupled receptor class C group 5 member D
Cluster of differentiation
Complete response
Overall response rate
Very good partial response
Newly diagnosed multiple myelom
Transplant ineligible
Relapsed or refractory multiple myeloma
Extramedullary disease
Grade
Adverse event
Progression free survival
Overall survival
Duration of response
Not reached
Chimeric antigen receptor
Grade
Cereblon E3 ligase modulatory drug
Immunomodulatory drug
Subcutaneous
Intravenous
Step up dosing
Cytokine release syndrome
Immune effector cell-associated neurotoxicity syndrome
Next generation sequencing
Next generation flow
Author contributions
Both authors were directly involved in writing and revising the manuscript, and production of tables, which were reviewed by all authors.
Funding
This work received no funding.
Data availability
No datasets were generated or analysed during the current study.
Declarations
Competing interests
The authors declare no competing interests.
Ethics approval and consent to participate
The current work was exempted from requiring Ethics approval and consent to participate based on institutional guidelines.
Consent for publication
Not applicable.
Competing interests
MB reports Consultancy: AbbVie, J&J, Sanofi-Genzyme; Advisory Boards: Janssen Biotech, J&J, Sanofi-Genzyme, Pfizer, Prothena, AbbVie, Legend Biotech; Research Grants: Pfizer, J&J; Scientific Advisory Board seat: Xilis Inc.; DSMB: Delta-Fly; IRCs: Parexel International. PTN reports no financial conflict of interest.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
1. Kazandjian D, Diamond B, Hoffman J, et al. A phase 2 trial of abbreviated fixed-duration (default 4 cycles) linvoseltamab immuno-consolidation to deepen responses post newly diagnosed multiple myeloma combination therapy for minimal residual disease positivity (the IMMUNOPLANT Study). Blood. 2025;146(suppl 1):248–9. 10.1182/blood-2025-248.
2. Manier S, Lambert J, Macro M, et al. A phase 2 study of teclistamab in combination with daratumumab in elderly patients with newly diagnosed multiple myeloma: the IFM2021-01 TECLILLE trial, cohort A. Blood. 2025;146(suppl 1):367–8. 10.1182/blood-2025-367.
3. Mateos MV, Bahlis N, Perrot A, et al. Teclistamab plus daratumumab versus daratumumab, pomalidomide, and dexamethasone or daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma: MajesTEC-3 phase 3 study results. Blood. 2025;146(suppl 1):LBA–6. 10.1182/blood-2025-LBA-6.
4. Costa LJ, Bahlis NJ, Perrot A, et al. Teclistamab plus daratumumab in relapsed or refractory multiple myeloma. N Engl J Med. 2025. 10.1056/NEJMoa2514663.
5. Suvannasankha A, Kaufman J, Badros A, et al. Safety and efficacy of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma: results from the phase 1b MagnetisMM-30 trial. Blood. 2025;146(suppl 1):100–1. 10.1182/blood-2025-100.
6. Bahlis NJ, Costello CL, Raje NS, et al. Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial. Nat Med. 2023;29(10):2570–6. 10.1038/s41591-023-02589-w.
7. Usmani SZ, Cohen YC, Kumar S, et al. Talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma and extramedullary disease: extended follow-up from the RedirecTT-1 study. Blood. 2025;146(suppl 1):698. 10.1182/blood-2025-698.
8. Kumar S, Mateos MV, Ye JC, et al. Dual Targeting of Extramedullary Myeloma with Talquetamab and Teclistamab. N Engl J Med. 2026;394(1):51–61. 10.1056/NEJMoa2514752.
9. Moreau P, Mateos MV, Goldschmidt H, et al. Outcomes of Patients With Extramedullary Disease in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma From the Pooled LocoMMotion and MoMMent Studies. Clin Lymphoma Myeloma Leuk. 2025;25(9):646–e6551. 10.1016/j.clml.2025.03.014.
10. Harrison S, Ho PJ, Lim SL, et al. Minimal residual disease (MRD)-negative outcomes following a novel, in vivo gene therapy generating anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells in patients with relapsed and refractory multiple myeloma (RRMM): preliminary results from inMMyCAR, the first-in-human phase 1 study of KLN-1010. Blood. 2025;146(suppl 2):LBA–1. 10.1182/blood-2025-LBA-1.
11. Bjorklund CC, Kang J, Amatangelo M, et al. Iberdomide (CC-220) is a potent cereblon E3 ligase modulator with antitumor and immunostimulatory activities in lenalidomide- and pomalidomide-resistant multiple myeloma cells with dysregulated CRBN. Leukemia. 2020;34(4):1197–201. 10.1038/s41375-019-0620-8.
Associated Data
Data Availability Statement
No datasets were generated or analysed during the current study.