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Targets Selection for Precision Therapy of Relapsed/Refractory Multiple Myeloma: the Latest Advancements

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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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Acknowledgements

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Funding

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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Correspondence to Lin Ma or Baoshan Liu.

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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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