Opinion Statement
According to the guidelines, the primary treatment for multiple myeloma is still based on drugs such as carfilzomib, lenalidomide, or daratumumab. However, patients with relapsed/refractory multiple myeloma (RRMM) may be insensitive or develop resistance to the above therapeutic medications. Thus, formulating standardized and rational treatment regimens for such patients remains an area for consideration. Multidrug combinations are available for the therapy of patients with relapsed/refractory multiple myeloma to improve their clinical outcome and prevent the occurrence of multidrug resistance. For instance, combination therapy with immunomodulators, proteasome inhibitors, and CD38 monoclonal antibodies. With the development of genomics and molecular diagnostic technologies, RRMM has entered the era of precision therapy. Targeted immunotherapeutic drugs such as monoclonal antibodies, bispecific antibodies, antibody–drug conjugates (ADCs), and chimeric antigen receptor-T (CAR-T) cells have shown promising clinical response rates and favorable safety profiles in several clinical and experimental studies. These cutting-edge medicinal treatments may provide new hope for a cure for RRMM. However, the choice of treatment regimen still needs to adhere to the principle of individualization. Generally, we recommend treatment with drugs of a new generation or novel mechanism of action for patients with RRMM who are first relapsed, such as next-generation proteasome inhibitors, next-generation immunomodulators, and CD38-based monoclonal antibody regimens. For multiple relapsed RRMM, we recommend choosing a combination regimen or participating in relevant clinical trials. Additionally, monoclonal antibodies have become the standard of care for patients with RRMM. With the introduction of CAR-T therapy, ADCs, and bispecific antibodies, RRMM patients are expected to achieve deep remissions and long-term survival again.
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Data Availability
No datasets were generated or analysed during the current study.
Abbreviations
- MM :
-
Multiple myeloma
- RRMM :
-
Refractory multiple myeloma
- CAR-T :
-
Chimeric antigen receptor-T
- ADCs :
-
Antibody-drug conjugates
- BCMA :
-
B-cell maturation antigen
- ORR :
-
Overall response rate
- CR :
-
Complete response
- sCR :
-
Stringent CR
- PFS :
-
Progression-free survival
- OS :
-
Overall survival
- AEs :
-
Adverse events
- PR :
-
Partial response
- DOR :
-
Duration of response
- MRD :
-
Minimal residual disease
- GSIs :
-
Gamma Secretase Inhibitors
- CRS :
-
Cytokine release syndrome
- FDA :
-
Food and drug administration
- GSIs :
-
Gamma Secretase Inhibitors
- VGPR :
-
Very good partial response
- GPRC5D :
-
G protein-coupled receptor, class C group 5 member D
- TEAEs :
-
Treatment-emergent adverse events
- KM :
-
Kaplan-Meier
- TRAEs :
-
Treatment-related adverse effects
- PD-1 :
-
Programmed cell death 1
- PD-L1 :
-
Programmed death ligand 1
- MTD :
-
Maximum tolerance dose
- RP2D :
-
Recommended phase 2 dose
- DLT :
-
Dose-limiting toxicities
- SAE :
-
Serious adverse event
- CRR :
-
Clinical reportable range
- CBR :
-
Clinical benefit rate
- DCR :
-
Disease control rate
- AUC :
-
Area under the curve
- TTP :
-
Time to progression
- TTF :
-
Time to treatment failure
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This study was supported by grants from the Youth Fund of the National Natural Science Foundation of China (grant number: No. 82305127), China.
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Zhen Wang: Writing-original draft, Review & editing, Formal analysis, Literature search. Yanqi Song: Writing-review & editing, Formal analysis. Honglei Guo: Writing-literature search, Formal analysis. Yuting Yan: Writing-investigation, Review. Lin Ma: Writing-revise, Supervision, Funding acquisition. Baoshan Liu: Writing-review & editing, Conceptualization, Supervision.
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Wang, Z., Song, Y., Guo, H. et al. Targets Selection for Precision Therapy of Relapsed/Refractory Multiple Myeloma: the Latest Advancements. Curr. Treat. Options in Oncol. 26, 128–141 (2025). https://doi.org/10.1007/s11864-025-01290-z
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DOI: https://doi.org/10.1007/s11864-025-01290-z