At the recently concluded ASH (American Society of Hematology) Annual Meeting,Multiple Myeloma (MM)Has witnessed several research advances, includingDoubleAnti-（TargetedBCMA, GPRC5D, etc.), CAR-T therapy, etc., such as pharmaceutical companies in ChinaLeads BiolabsBrought byGPRC5D/CD3 Bispecific AntibodyLBL-034According to the latest report, the high-dose group reachedORRRate90.9%The astonishing efficacy, at the same time,80.0% of patients achieved minimal residual disease (MRD)-negative status.。Johnson & JohnsonBCMA/CD3 Bispecific Antibody TECVAYLI Combined with CD38 Monoclonal AntibodyDARZALEXIn relapsed/refractory multiple myeloma (RRMM）Second-line Treatment for PatientsIIIPeriodThe research also brings positive results:Compared with standard treatment, the 36-month PFS rate in the combination therapy group reached 83.4%, with a hazard ratio (HR) of 0.17.The disclosure of multiple research advances marks MMTherapeutic AreasA new landscape is about to emerge. Taking this opportunity, let's comprehensively understand the evolution of MM treatment.Discovery and Early Treatment of MM
The discovery of MM can be traced back toIn 1844,At that timeUnited KingdomFamous SurgeryDoctor Samuel Solly documented a case of a 39-year-old female.Case: The patient was admitted due toParalyzed due to years of severe back pain and multiple fractures, eventually passed away in the hospital.Patient'sAutopsy showsBone Marrow Abnormalities，It was discovered inARed Gel-like SubstanceSolly referred to it as mollities ossium (abnormal bone softness), which is one of the earliest descriptions of MM.Today, we recognize that this is a condition originating fromMalignant Tumor of Plasma Cells，Commonly complicated by bone disease, kidney damage, infection, anemia, and other symptoms, leading to a decline in overall survival rate and quality of life.Epidemiological studies have shown that MMAboutOccupying10-15% of hematologic malignancies, isThe Second Most Common Blood Cancer Globally。Before the 1960s, there was no corresponding treatment for MM.The median overall survival is only about 6 months.Until around 1970,Chemotherapy Drug Melphalan（Melphalan), Cyclophosphamide combined withThe birth and subsequent application of combination therapies have ushered in the modern era of MM treatment.Around 1990,Autologous Hematopoietic Stem Cell Transplantation (ASCT)The emergence of technology has extended the median OS of suitable transplant patients to 4-5 years, becomingMM TreatmentThe gold standard,It remains an important part of MM treatment to this day.At the end of the 1990s, the first-generation immunomodulatory agent thalidomide emerged, causing a significant shift in the treatment paradigm for MM.。Immunomodulators and Proteasome Inhibitors
Reshaping the MM Treatment Landscape
In 1998,Thalidomide Approved by FDAListed,Used for the treatment of MM.The drug works through proteins.cereblon(Encoded by CRBN)Degraded two key transcription factors of myeloma, Ikaros and Aiolos, causing a significant shift in the treatment landscape for MM. LaterPeople have further developed lenalidomide, which has better efficacy in treating multiple myeloma, based on thalidomide.(2005 Market Launch)And Pomalidomide(2013 Market Launch)，Now,These twoPaymentMedication remains the treatmentMMTheCornerstone drugs.InThalidomideWait for immunityWhile modulators improve patients' clinical outcomes, proteasome inhibitors also play a role. In 2003, the first proteasome inhibitor —BortezomibApproved for marketing, becomingNew DiagnosisMMThe first-line recommended treatment regimen.In 2012, the second generationThe proteasome inhibitor carfilzomib was approved for marketing; in 2015, ixazomib was approved for marketing.The application of immunomodulatory agents and proteasome inhibitors has greatly improved the outcomes for MM patients.Prognosis，Median survival extended from approximately 3 years to 8-10 years.However, most patients will eventually relapse, creating an urgent need for novel treatments that are well-tolerated and provide durable remission.Monoclonal Antibody/Bispecific Antibody
Brings New Hope to Patients with Relapsed and Refractory Conditions
In 2015, Johnson & Johnson'sDaratumumab（Darzalex）Approved by the FDA for marketing, used forMonotherapy for MM patients who have received at least three prior treatments (including proteasome inhibitors and immunomodulatory agents) has becomeThe FirstCD38-targeted monoclonal antibody drugs approved for MM.In 2016,FDA ApprovalDaratumumabIn combination with lenalidomide and dexamethasone, or in combination with bortezomib and dexamethasone, used for second-line treatment.MM(Patients who have previously received at least one therapy).Clinical studies have shown that,In newly diagnosed cases unsuitable for transplantationMMAmong patients, compared with traditional regimens,DaratumumabThe combination regimen nearly doubled the PFS and also significantly improved the OS.DaratumumabThe emergence has completely revolutionizedMMThe treatment landscape isMMA milestone breakthrough in the field of immunotherapy.In 2020, Sanofi's CD38 monoclonal antibodyIsatuximab（Sarclisa）Approved by the FDA for marketing,With Pomalidomide and DexamethasoneCombination therapy for R/R MM patients who have previously received at least two prior treatments (including lenalidomide and proteasome inhibitors).According to the Phase III clinical study,Compared with the standard treatment of pomalidomide + dexamethasone, isatuximab combined with pomalidomide + dexamethasone significantly prolongs PFS.Median PFS was 11.53 months vs 6.47 months(HR=0.596, 95%CI: 0.44-0.81, p=0.001), while significantly improving the overall response rate,ORR was 60.4% vs 35.3%（p<0.0001)。mOS24.6 months vs 17.7 months（95%CI，14.4-26.2）。CD38Monoclonal AntibodyMM represented byTreatment PlanWith broadTheMarket Potential.DaratumumabMore than a decade after its listing,Still maintaining a high year-on-year growth rate of 22%,It is a veritable blockbuster.Sanofi's IsatuximabEqually impressive potential。In terms of bispecific antibodies, in 2022,Johnson & Johnson'sTislelizumab (Tecvayli）Approved by the FDA for marketing, used forHaving previously received at least four lines of therapy (including proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies)R/R MMPatient, becomingThe World's First Approved BCMA/CD3 Bispecific Antibody。In 2023,Pfizer'sBCMA/CD3 Bispecific AntibodyEnatuzumab (Elrexfio）Granted FDA Accelerated Approval,Used to treat patients who have received at least three prior lines of therapyR/R MMPatient.AndTelitumomabThe difference is,In terms of medication administration,Enatuzumab AdoptedSubcutaneous injection method, more convenient to use.In 2023, Johnson & Johnson'sGPRC5D/CD3Bispecific AntibodyTaqiutumab（Talvey）Granted FDA Accelerated Approval forHave previously received at least three lines of therapy (including proteasome inhibitors, immunomodulatory agents、Anti-CD38 antibody)R/R MMPatient.In July 2025, Regeneron'sBCMA/CD3Bispecific AntibodyLynozyficGranted FDA Accelerated Approval,For the treatment of R/R MM that has been previously treated with at least four lines of therapyPatient.TheseBispecific AntibodyDrug inPast Medical HistoryHaving received a variety of treatment regimensR/R MM中Can alsoAchieved better therapeutic effects，Such patientsOverall survival was significantly improved.。CAR-T Brings "Cure" Dawn
CAR-T can be regarded as a game-changer in the treatment of MM.Currently, in the MM fieldFour CAR-T products have been approved for marketing, all targetingB-Cell Maturation Antigen（BCMA）。In 2021, BMS/Bluebird Bio'sAbecmaApproved by the FDA for marketing,For the treatment of R/R MM patients who have previously received at least 4 lines of therapy (including immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies).Patient.Subsequently, there is also3 ProductsTargetedBCMATheCAR-T TherapyApproved for TreatmentR/R MM，They are Legend Biotech/Johnson & Johnson'sCarvykti(Cilta-cel)，In 2022, the FDA）、Reindeer Bio'sFucos(Idecabtagene Vicleucel,In 2023, NMPA）、CARsgen TherapeuticsSaikaze(Zevorcleucel,In 2024, NMPA), theseInnovative TherapyIn heavily pretreatedR/R MMIn patients, it showedLeads BiolabsDeep and lasting relief。In addition to single-target CAR-T, at this year's ASH Annual Meeting,AstraZeneca Brought Its New Dual-TargetBCMA/CD19 CAR-T AZD0120InR/R MMAdvances in the Field of Treatment.In the treatment of R/R MMIn the Ib phase study, AZD0120AchievedORRFor100%Breakthrough data.In summary,With the proteasome inhibition, immunomodulators, CD38 monoclonal antibodies, bispecificAnti-, and the continuous introduction of new mechanism drugs such as CAR-T,MMTreatment has entered a new stage of "optimization and integration" from "revolutionary breakthrough."The Core of the Future isBy optimizing the combination and sequence of these therapies and managing their toxicity,Ultimately transform MM into a disease that can be controlled long-term or even cured.1.A first-in-human, phase I/II, open-label, multicenter, dose escalation and expansion study of LBL-034, a conditionally activated bispecific antibody targeting GPRC5D and CD3 with a 2:1 format, in patients with relapsed/refractory multiple myeloma.2.Bcma/cd3 and gprdc5d/cd3 bispecific antibodies for use in cancer therapy.3.https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20250211152345189.html.*Disclaimer: This article is only intended to introduce research progress in the pharmaceutical and disease fields, briefly describe research overviews, or share pharmaceutical-related information. It neither recommends any treatment or diagnostic plans nor constitutes any advice on related investments. If there are any omissions in the content, please feel free to communicate and point them out!
