China-US Multiple Myeloma Treatment Milestones from 2015-2025: The Era of Immunomodulators and Bispecific Antibodies

Multiple myeloma (MM) is a malignant hematological tumor caused by abnormal proliferation of plasma cells in the bone marrow, with diverse clinical manifestations often accompanied by complications such as skeletal damage, anemia, and renal impairment. Without timely intervention, patients in the progressive stage have extremely short survival periods. From 2015 to 2025, with the rapid development of medical technology, the emergence of new drugs, and the continuous update of diagnostic and treatment concepts, the diagnostic criteria for MM have become increasingly refined, and treatment regimens have become more individualized. Both China and the US have made breakthrough progress in exploring and practicing standard therapies, significantly improving patients' survival periods and quality of life. DengyueMed will systematically elaborate on the diagnostic developments of MM over the decade, milestones in therapies in China and the US, comparisons of current optimal treatments in guidelines, future trends, and a summary outlook, outlining the evolution and key breakthroughs in the diagnostic and treatment field.

Diagnostic Developments and Changes in Multiple Myeloma from 2015 to 2025

Before 2015, the diagnosis of MM mainly relied on the traditional CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone destruction), which only targeted symptomatic patients with clear organ damage. Many patients in the asymptomatic or subclinical stages were easily missed, losing opportunities for early intervention. From 2015 to 2025, the diagnostic system for MM achieved a fundamental shift from "symptom-driven" to "risk-oriented," with comprehensive optimization of diagnostic indicators, testing technologies, and stratification standards. The core changes unfolded in the following three dimensions.

First, the update and refinement of diagnostic criteria incorporated early risk signals into the diagnostic scope. The new diagnostic criteria formulated by the International Myeloma Working Group (IMWG) in 2014 added three myeloma-defining events (MDEs) on top of the traditional CRAB symptoms, including bone marrow clonal plasma cells ≥60%, free light chain ratio κ/λ ≥100 or ≤0.01, and MRI detection of more than one focal lesion (diameter >5 mm). This standard was gradually promoted globally after 2015, enabling early identification of some high-risk smoldering multiple myeloma (SMM) patients without symptoms. Over the decade, diagnostic criteria continued to be refined, and after 2020, diagnostic thresholds for different risk stratifications were further clarified, incorporating cytogenetic abnormalities, serum β2-microglobulin levels, and other auxiliary indicators, achieving the diagnostic goals of "early detection, early diagnosis, early intervention."

Second, the iterative upgrade of testing technologies improved diagnostic accuracy and comprehensiveness. In 2015, bone marrow morphology examination, serum protein electrophoresis, and conventional chromosome banding techniques were still the core means of MM diagnosis, but they had limitations such as low sensitivity and high miss rates—conventional chromosome banding could only detect 30%-50% of chromosomal abnormalities and had weak detection capabilities for extramedullary lesions. Over the decade, various precise testing technologies became widely adopted: fluorescence in situ hybridization (FISH) increased the detection rate of chromosomal abnormalities to over 90%, becoming the gold standard for cytogenetic testing; next-generation sequencing (NGS) achieved high-sensitivity detection of tumor cell clonality, with sensitivity up to 10⁻⁶, identifying minimal residual disease (MRD) missed by traditional methods; the promotion of imaging technologies such as PET-CT and whole-body MRI effectively addressed the missed diagnosis of extramedullary lesions and patchy bone marrow infiltration, detecting lesions as small as 4 mm and providing more reliable imaging evidence for diagnosis and staging. In addition, the standardization of tests such as serum free light chain quantification and immunofixation electrophoresis further improved the detection rate of M protein, enabling about 95% of patients to obtain clear diagnostic clues through serological tests.

Third, the popularization of stratified diagnostic concepts laid the foundation for individualized treatment. In 2015, MM diagnosis simply distinguished between symptomatic and asymptomatic, without fully considering disease heterogeneity. Over the decade, with in-depth research into the pathogenesis of MM, stratified diagnosis became increasingly refined, classifying patients into low-risk, intermediate-risk, and high-risk based on indicators such as cytogenetic abnormalities (e.g., t(11;14), del(17p)), serum markers (β2-microglobulin, LDH, CRP), and MRD status. Patients in different strata have significant differences in treatment regimens and prognoses—high-risk patients are prone to relapse with short survival periods, requiring more intensive treatment strategies, while low-risk patients can use milder treatments to avoid adverse reactions from overtreatment. The popularization of this stratified diagnostic concept shifted MM diagnosis and treatment from "one-size-fits-all" to "individualized precision strategies," significantly improving treatment outcomes.

Milestone Events in Standard Therapies for Multiple Myeloma in China and the US Over the Past Decade

From 2015 to 2025, China and the US advanced in parallel in exploring standard therapies for MM, leveraging their respective advantages in clinical research and drug development to achieve a leap from traditional chemotherapy to immunotherapy, targeted therapy, and cellular therapy. A series of milestone events emerged, driving continuous updates and iterations of standard therapies, as detailed below.

US Milestone Events

1. 2015: First approval of CD38-targeted monoclonal antibody, ushering in a new era of immunotherapy. Johnson & Johnson's daratumumab (Darzalex) was approved by the FDA for monotherapy in MM patients who had received at least three prior treatments (including proteasome inhibitors and immunomodulators), becoming the first CD38-targeted monoclonal antibody approved for MM. It broke the limitations of traditional chemotherapy and proteasome inhibitors, providing new treatment options for relapsed/refractory MM (R/R MM) patients. Its unique mechanism directly kills CD38-positive plasma cells and is less likely to produce cross-resistance.
2. 2017: Proteasome inhibitor combined with immunomodulator becomes the standard induction regimen for newly diagnosed MM. The FDA approved bortezomib (first-generation proteasome inhibitor) combined with lenalidomide (immunomodulator) + dexamethasone (VRd regimen) as the first-line standard induction regimen for newly diagnosed MM patients. This regimen increased the complete response (CR) rate to over 30% and extended median progression-free survival (PFS) to over 2 years, replacing the traditional MP regimen (melphalan + prednisone) and becoming the core induction regimen for transplant-eligible patients, marking the entry of MM into the era of "dual-drug combination + glucocorticoids" intensive treatment.
3. 2020: CAR-T cell therapy approved, bringing hope for cure in R/R MM patients. BMS/Bluebird Bio's Abecma (BCMA-targeted CAR-T therapy) was approved by the FDA for R/R MM patients who had received at least 4 prior lines of treatment, becoming the first CAR-T product approved for MM. It demonstrated significant efficacy in clinical studies, with some patients achieving long-term remission, breaking the deadlock of no effective treatments for R/R MM patients and opening a new chapter in MM cellular therapy.
4. 2022: BCMA/CD3 bispecific antibody approved, filling a new gap in immunotherapy. Johnson & Johnson's teclistamab (Tecvayli) was approved by the FDA, becoming the world's first approved BCMA/CD3 bispecific antibody for R/R MM patients who had received at least four prior lines of treatment (including proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies). It combines targeting and immune killing activity, providing new directions for multi-line treatment failures in R/R MM patients. Subsequently, multiple bispecific antibodies from companies like Pfizer and Johnson & Johnson were approved, enriching immunotherapy options.
5. 2024: MRD-guided treatment strategies incorporated into guidelines, promoting the implementation of precision therapy. The FDA incorporated MRD testing results into MM treatment guidelines, clarifying that MRD-negative patients can appropriately reduce treatment intensity, while MRD-positive patients require intensified treatment. This "dynamic monitoring + individualized adjustment" strategy further enhanced treatment precision, reducing issues of overtreatment and undertreatment. It became a new paradigm for MM treatment. Meanwhile, the NCCN guidelines (version 4.2026) further updated the applicable scenarios for bispecific antibodies and CAR-T therapies, refining stratified treatment strategies.

China Milestone Events

1. 2017: Bortezomib and lenalidomide included in medical insurance, achieving a breakthrough in targeted drug accessibility. Previously, core targeted drugs for MM were expensive, unaffordable for most patients. In 2017, bortezomib and lenalidomide were officially included in the national medical insurance catalog, significantly reducing treatment costs and enabling more newly diagnosed and R/R MM patients to receive standardized targeted therapy. This shifted China's MM treatment from "chemotherapy-dominated" to "targeted therapy-dominated," significantly improving overall treatment levels, with combined drug treatment efficacy rates gradually approaching international levels (80%-95%).
2. 2020: China's independently developed CD38 monoclonal antibody approved, breaking the monopoly of imported drugs. Sepratinib (daratumumab biosimilar) was approved for marketing, becoming China's first independently developed CD38-targeted monoclonal antibody. Subsequently, multiple CD38 monoclonal antibody biosimilars were approved, not only reducing treatment costs but also promoting the popularization of immunotherapy in China, enriching treatment options for R/R MM patients. It also standardized the clinical application of diagnostic technologies such as serum free light chain testing and FISH.
3. 2022: Standardized promotion of autologous hematopoietic stem cell transplantation (ASCT), optimizing treatment paths for transplant-eligible patients. Previously, ASCT application in China was limited. In 2022, the Chinese Medical Doctor Association's Hematology Branch released the "Chinese Expert Consensus on Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma," clarifying the eligible population, operational standards, and post-transplant maintenance regimens for ASCT. This promoted its popularization in domestic hospitals at all levels, extending the median survival period for eligible young patients to over 5 years, approaching international advanced levels. It also refined supportive care regimens for complications such as skeletal damage and renal insufficiency.
4. 2023: China's independently developed CAR-T therapy approved, achieving a breakthrough in cellular therapy. Legend Biotech's Fucaso (equecabtagene autoleucel, BCMA-targeted CAR-T therapy) was approved by the NMPA, becoming China's first independently developed MM CAR-T product. Subsequently, CARsgen Therapeutics' zevorcabtagene autoleucel was approved, marking China's entry into the era of independent development in MM cellular therapy, breaking the monopoly of imported CAR-T products and bringing new hope to multi-line treatment failures in R/R MM patients. Meanwhile, domestic pharmaceutical company Vitti Biopharma's GPRC5D/CD3 bispecific antibody entered clinical research stages, showing promising efficacy prospects.
5. 2024: Update of the "Chinese Guidelines for the Diagnosis and Treatment of Multiple Myeloma (2024 Edition)," aligning with international guidelines. The new guidelines incorporated new treatment methods such as bispecific antibodies and CAR-T, refined stratified treatment strategies, clarified individualized treatment regimens for patients of different risks and ages, and included precise testing methods such as MRD testing and PET-CT in routine diagnostic processes. It standardized differential diagnostic criteria for monoclonal gammopathy of undetermined significance (MGUS), AL amyloidosis, etc., promoting China's MM diagnosis and treatment to gradually align with international standards, achieving "precise, standardized, individualized" care.

Comparison of Current Optimal Treatments in China-US Guidelines

Currently, the US NCCN guidelines (version 4.2026) and China's "Guidelines for the Diagnosis and Treatment of Multiple Myeloma (2024 Edition)" both focus on stratified treatment for MM, with consistent core principles—formulating individualized treatment regimens based on patients' age, performance status, risk stratification, and MRD status. However, due to differences in medical resources, drug accessibility, and patient population characteristics between the two countries, there are certain distinctions in the selection of optimal treatment regimens, mainly in the following four aspects. Overall, both center on "targeted + immune" therapies, balancing efficacy and safety.

I. Comparison of Optimal Treatments for Newly Diagnosed MM Patients

US NCCN Guidelines Recommendation: For transplant-eligible young patients (≤65 years), the first-line induction regimen prefers the VRd regimen (bortezomib + lenalidomide + dexamethasone), followed by ASCT after 4-6 cycles of induction, with lenalidomide maintenance for over 2 years post-transplant. If MRD-positive, induction can be intensified or switched to bispecific antibody combinations. For transplant-ineligible elderly patients (>65 years), the Rd regimen (lenalidomide + dexamethasone) or D-Rd regimen (daratumumab + lenalidomide + dexamethasone) is preferred, emphasizing long-term maintenance until disease progression, with drug dose adjustments based on renal function.

Chinese Guidelines Recommendation: For transplant-eligible young patients, the first-line induction regimen also prefers VRd, consistent with US guidelines, with lenalidomide maintenance post-ASCT, but duration can be adjusted to 1-2 years based on economic conditions and tolerability. For transplant-ineligible elderly patients, due to some having renal insufficiency and poor performance status, bortezomib-based combinations (e.g., bortezomib + dexamethasone, VD regimen) are preferred. If well-tolerated, they can be combined with lenalidomide or CD38 monoclonal antibodies. Supportive care is emphasized to prevent infections, fractures, etc. For patients with limited economic conditions, traditional chemotherapy can be used as a transition, gradually upgrading to targeted therapy, balancing efficacy and accessibility.

II. Comparison of Optimal Treatments for Relapsed/Refractory MM Patients

US NCCN Guidelines Recommendation: For patients relapsing after first-line treatment, novel drug combinations are prioritized, such as bispecific antibody regimens (teclistamab + dexamethasone, elranatamab + dexamethasone), CAR-T cell therapy (for multi-line relapses, MRD-positive patients). If unable to tolerate novel drugs, switch proteasome inhibitor or immunomodulator types (e.g., carfilzomib replacing bortezomib, pomalidomide replacing lenalidomide). Emphasize dynamic MRD monitoring and adjust regimens based on MRD status. Studies presented at the 2025 ASH annual meeting showed that bispecific antibody combined with CD38 monoclonal antibody regimens demonstrated excellent efficacy in second-line RRMM treatment, with a 36-month PFS rate of 83.4%, incorporated into guideline recommendations.

Chinese Guidelines Recommendation: For relapsed/refractory patients, prioritize domestically accessible drug combinations, such as CD38 monoclonal antibody + lenalidomide + dexamethasone (D-Rd regimen), bortezomib + pomalidomide + dexamethasone (VPd regimen). For multi-line relapses without effective options, choose China's independently developed CAR-T therapies or bispecific antibodies. Encourage participation in clinical trials to explore new regimens. For patients with limited economic conditions, use traditional chemotherapy to control disease and relieve symptoms, focusing on complication treatment to improve quality of life.

III. Comparison of Optimal Treatments for High-Risk MM Patients

Both China and US guidelines clearly state that high-risk MM patients (with cytogenetic abnormalities such as del(17p), t(4;14)) require intensive treatment strategies, but specific regimens differ. US NCCN Guidelines Recommendation: For high-risk patients, induction prefers VRd combined with CD38 monoclonal antibody, with lenalidomide + CD38 monoclonal antibody maintenance post-ASCT. Allogeneic hematopoietic stem cell transplantation can be considered (for young patients in good condition). Long-term MRD monitoring; if persistently MRD-positive, switch regimens promptly. Emphasize full-course intensive treatment to reduce relapse risk.

Chinese Guidelines Recommendation: For high-risk patients, induction prefers intensified VRd, with lenalidomide maintenance post-ASCT. Due to limited allogeneic transplantation in China (donor shortages, high costs), it is only recommended for select eligible patients. Emphasize cytogenetic testing. For patients unable to tolerate intensive treatment, appropriately reduce intensity, balancing efficacy and safety. Focus on monitoring renal function, serum calcium, etc., to prevent complication exacerbation.

IV. Comparison of Supportive Care and Follow-Up

US NCCN Guidelines emphasize long-term follow-up and supportive care, recommending MRD testing, serum protein electrophoresis, complete blood count, etc., every 3 months, and PET-CT annually. Routinely administer bisphosphonates to prevent skeletal damage, immunoglobulins to prevent infections, and standardize management for complications like anemia and renal insufficiency. Emphasize full-course quality of life management and provide multilingual patient guides to improve adherence.

Chinese Guidelines, considering domestic medical resource realities, recommend routine follow-up every 3-6 months, with MRD testing frequency adjusted by risk stratification and treatment stage (every 3 months for high-risk, every 6 months for low-risk). Supportive care focuses on common complications like skeletal damage and infections, with routine bisphosphonates. Strengthen patient education on dietary adjustments and rehabilitation, avoiding fried, spicy foods to promote recovery. For grassroots hospital patients, simplify follow-up processes to enhance accessibility.

Future Trend Predictions

Based on the development trends in MM diagnosis and treatment over the past decade, as well as current clinical research progress, post-2025, MM diagnosis and treatment will continue to evolve toward "more precise, more efficient, safer, more accessible" directions. Core trends are mainly in the following five aspects, expected to further break through existing treatment bottlenecks and advance MM from "incurable" to "controllable and curable."

First, precision stratification and MRD-guided treatment become mainstream. With further popularization of NGS, FISH, etc., stratified diagnosis will be more refined, not only based on cytogenetic abnormalities and serum markers but also incorporating genomic sequencing results, tumor microenvironment features, etc., achieving "individualized stratification." Meanwhile, MRD testing will become a routine follow-up indicator, enabling "dynamic monitoring + real-time regimen adjustment," further improving treatment precision, reducing overtreatment and undertreatment. For persistently MRD-negative patients, "drug discontinuation observation" may be possible, improving quality of life and reducing costs.

Second, new drug development focuses on "high efficiency, low toxicity, broad spectrum." Future MM drug R&D will concentrate on bispecific antibodies, trispecific antibodies, antibody-drug conjugates (ADCs), novel proteasome inhibitors, etc., further enhancing targeting and reducing adverse reactions—bispecific and trispecific antibodies will evolve toward multi-target directions (e.g., BCMA/CD3/GPRC5D trispecific), covering more resistant patients; ADCs will achieve "precise tumor cell killing, protecting normal cells," reducing chemotherapy-related adverse reactions. Meanwhile, in-depth research into resistance mechanisms will develop new drugs to reverse resistance, addressing treatment dilemmas for R/R MM patients. Bispecific antibody studies presented at the 2025 ASH annual meeting showed ORR rates up to 90.9% in high-dose groups, with 80.0% achieving MRD negativity, indicating promising prospects for new drugs.

Third, cellular therapy evolves toward "safer, more convenient, more accessible." CAR-T cell therapy will be further optimized to reduce treatment-related adverse reactions (e.g., cytokine release syndrome, neurotoxicity), simplify preparation processes, shorten preparation times, and lower costs, shifting CAR-T from "niche treatment" to "routine treatment." Additionally, off-the-shelf CAR-T, TCR-T, and other novel cellular therapies will gradually enter clinical use, solving donor shortage issues and expanding applicability. Dual-target CAR-T (e.g., BCMA/CD19 CAR-T) research shows significant progress, potentially achieving 100% ORR breakthroughs.

Fourth, the gap in China-US diagnosis and treatment gradually narrows, achieving homogenization. With the continuous emergence of China's independently developed drugs and ongoing improvements in medical insurance policies, accessibility of new drugs (bispecific antibodies, CAR-T) will significantly increase, approaching US levels. Meanwhile, China will further promote precise testing technologies and standardized diagnostic processes, strengthen international clinical research collaborations, learn from US advanced experiences, optimize stratified treatment strategies, and narrow gaps in high-risk patient treatment, supportive care, etc., achieving homogenized, standardized MM diagnosis and treatment, benefiting more Chinese patients with precision medicine.

Fifth, more emphasis on prevention and early intervention. With in-depth research into MM pathogenesis and popularization of screening technologies, future efforts will gradually establish early screening systems for MM, conducting regular screenings for high-risk groups (e.g., MGUS patients, those with family history), achieving "early detection, early intervention." Meanwhile, for mechanisms of MGUS progression to MM, preventive drugs will be developed to reduce progression risks, addressing the root cause to decrease MM incidence. MGUS progresses to SMM at 1% per year, and SMM has a 10% annual progression to symptomatic MM in the first 5 years; early intervention is expected to significantly reduce this rate.

Summary and Outlook

The decade from 2015 to 2025 has been one of leapfrog development in the field of MM diagnosis and treatment, with core changes reflected in "diagnosis from crude to precise, treatment from traditional to novel, concepts from uniform to individualized." In diagnosis, upgrading from traditional CRAB criteria to a "risk-oriented" precise diagnostic system, with iterative testing technologies and popularization of stratified diagnosis, achieved early identification and precise stratification of MM, effectively reducing missed and misdiagnoses, laying a solid foundation for individualized treatment. In treatment, shifting from chemotherapy-dominated to "targeted therapy + immunotherapy" as the core, combined with ASCT, CAR-T cellular therapy, and other comprehensive modalities, the emergence of new drugs and improvements in medical insurance policies significantly improved treatment outcomes and drug accessibility, extending MM patients' median survival from 3-5 years a decade ago to 8-10 years, with some low-risk patients achieving long-term remission. Combined drug treatment efficacy rates have reached 80%-95%, and complete response rates have increased to 15%-50%.

Both China and the US have achieved remarkable accomplishments in exploring standard MM therapies over the past decade—the US, relying on strong drug R&D and clinical research capabilities, pioneered new treatment methods such as bispecific antibodies and CAR-T, formulating refined stratified treatment guidelines and leading global MM diagnosis and treatment directions; China, based on its own medical resource realities, through medical insurance negotiations and independent R&D, gradually improved new drug accessibility, promoted standardized diagnostic processes, narrowed the gap with international advanced levels, achieving a shift from "following" to "running alongside." Independently developed CAR-T and bispecific antibody products gradually broke import monopolies, enabling more patients to afford precision treatment.

At the same time, we should soberly recognize that challenges remain in the MM diagnosis and treatment field: high-risk patients still have high relapse rates and lack effective curative means; some new drugs (e.g., CAR-T, bispecific antibodies) have high treatment costs, with accessibility needing further improvement globally; research into resistance mechanisms requires deepening, with limited treatment options for R/R MM patients; treatment for complications such as extramedullary lesions and renal insufficiency still needs optimization.

Looking to the future, with the continuous development of precision medicine technologies, ongoing new drug R&D, and advancing clinical research, MM diagnosis and treatment will gradually break through existing bottlenecks: precision stratification will become more refined, MRD-guided dynamic treatment will become mainstream, achieving "one patient, one regimen"; new drugs and cellular therapy technologies will become safer, more efficient, and accessible, potentially achieving "functional cure" for MM; China-US diagnosis and treatment will further homogenize, with closer global collaborations jointly advancing progress in the MM field. Additionally, the establishment of early screening and prevention systems will reduce MM incidence at the source, keeping more people away from this malignant disease.

Overall, the changes in standard MM therapies over the past decade have significantly improved patients' survival periods and quality of life, demonstrating the power of medical progress. In the future, with continuous updates in diagnostic and treatment concepts and ongoing technological breakthroughs, MM is believed to gradually transform from an "incurable malignant tumor" to a "long-term controllable chronic disease," bringing more hope to global MM patients.