Multiple Myeloma Medical Services in China

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the uncontrolled proliferation of clonal plasma cells within the bone marrow. These abnormal cells produce monoclonal immunoglobulins (M-proteins) or free light chains, leading to end-organ damage—commonly summarized by the CRAB criteria: hyperCalcemia, Renal insufficiency, Anemia, and Bone lesions (e.g., lytic lesions, osteoporosis, pathologic fractures). Pathogenesis involves progressive genetic alterations—including translocations involving the immunoglobulin heavy chain locus (e.g., t(11;14), t(4;14)), deletions (e.g., del(17p)), and mutations in genes such as KRAS, NRAS, BRAF, and TP53—that drive dysregulated cell survival, proliferation, and evasion of apoptosis. The bone marrow microenvironment plays a critical role, with cytokines like IL-6, BAFF, and APRIL promoting myeloma cell growth and drug resistance. Epidemiologically, MM accounts for approximately 10% of all hematologic malignancies and 1–2% of all cancers globally. Incidence rises sharply with age, with a median diagnosis age of 69 years; it is rare under age 40. In China, age-standardized incidence is estimated at 1.0–1.3 per 100,000 person-years, with slightly higher rates in males than females. Known risk factors include monoclonal gammopathy of undetermined significance (MGUS)—a precursor condition present in >90% of MM cases—as well as advancing age, male sex, African ancestry (2–3× higher incidence vs. Asian or Caucasian populations), obesity, and occupational exposure to radiation or certain chemicals (e.g., benzene, pesticides). Family history also confers modest increased risk. Quality of life (QoL) is profoundly impacted: chronic bone pain, fatigue from anemia, recurrent infections due to immunoparesis, renal dysfunction requiring dialysis, and treatment-related toxicities (e.g., peripheral neuropathy, cytopenias, cognitive changes) contribute to physical disability, emotional distress, social withdrawal, and reduced functional independence. Patients often experience anxiety about disease progression and treatment burden, especially during prolonged maintenance therapy. Early diagnosis remains challenging due to nonspecific symptoms—such as fatigue, back pain, or recurrent sinusitis—which may delay referral to hematology. With modern therapies—including proteasome inhibitors (bortezomib, carfilzomib), immunomodulatory drugs (lenalidomide, pomalidomide), monoclonal antibodies (daratumumab, isatuximab), and emerging BCMA-targeted agents (bispecific antibodies, CAR-T cells)—median overall survival has improved to 7–10 years in fit patients, though outcomes vary significantly by cytogenetic risk, access to novel agents, and supportive care infrastructure.

Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by the proliferation of abnormal plasma cells in the bone marrow, leading to end-organ damage—including hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB criteria). As a hematologic malignancy managed primarily within hematology departments, MM requires a multidisciplinary, risk-adapted therapeutic strategy. Treatment goals include disease control, symptom alleviation, preservation of organ function, delay of progression, and—increasingly—achievement of deep, sustained remission or functional cure.

Conservative management forms the cornerstone of supportive care and remains essential throughout the disease continuum. This includes vigilant monitoring of renal function with hydration and avoidance of nephrotoxic agents (e.g., NSAIDs, IV contrast), prompt correction of hypercalcemia via intravenous saline hydration and bisphosphonates (e.g., zoledronic acid or denosumab), and management of anemia with erythropoiesis-stimulating agents (ESAs) or transfusions when indicated. Skeletal-related events are mitigated through routine skeletal surveys or low-dose whole-body CT/MRI, along with prophylactic radiation for impending pathologic fractures and orthopedic stabilization for lytic lesions causing mechanical instability. Infection prevention is critical: patients receive pneumococcal and influenza vaccinations, and long-term antimicrobial prophylaxis (e.g., trimethoprim-sulfamethoxazole) is recommended during immunosuppressive therapy. Nutritional support, physical rehabilitation, and psychosocial counseling further optimize quality of life and treatment tolerance.

Pharmacotherapy constitutes the primary disease-modifying intervention. First-line regimens for transplant-eligible patients typically consist of triplet combinations: bortezomib (a proteasome inhibitor), lenalidomide (an immunomodulatory drug), and dexamethasone (VRd); or daratumumab (anti-CD38 monoclonal antibody) plus VRd (D-VRd), which has demonstrated superior progression-free survival (PFS) and minimal residual disease (MRD) negativity rates in phase III trials. For transplant-ineligible patients, daratumumab–lenalidomide–dexamethasone (DRd) or lenalidomide–dexamethasone (Rd) with dose adjustments based on age and comorbidities are standard. Maintenance therapy—typically with lenalidomide post-autologous stem cell transplantation (ASCT)—significantly prolongs PFS and overall survival (OS). Relapsed/refractory MM is managed with novel agents including selinexor (XPO1 inhibitor), belantamab mafodotin (BCMA-targeting antibody-drug conjugate), and bispecific T-cell engagers (e.g., teclistamab, elranatamab). Chimeric antigen receptor T-cell (CAR-T) therapies targeting BCMA—such as idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel)—have shown unprecedented response durability in heavily pretreated patients, with median PFS exceeding 30 months in pivotal trials.

Surgical intervention plays a highly selective, palliative role. Orthopedic surgery is indicated for pathologic vertebral compression fractures unresponsive to kyphoplasty/vertebroplasty, unstable long-bone lesions at high risk of fracture, or spinal cord compression requiring decompression and stabilization. Surgical resection of solitary plasmacytomas (extramedullary or osseous) may be curative when complete resection is feasible and systemic disease is excluded. However, surgery is never used for systemic MM control; rather, it serves as adjunctive local therapy to restore mechanical integrity, relieve pain, and prevent neurologic compromise. All surgical candidates undergo thorough preoperative assessment of bone marrow reserve, coagulation status, and infection risk given their immunocompromised state.

China offers distinct advantages in MM care, driven by rapid integration of global innovations alongside domestic research leadership. Over 200 clinical trials for MM—including phase I–III studies of next-generation CAR-Ts (e.g., EMB-06, CT053), BCMA bispecifics, and oral proteasome inhibitors—are actively recruiting across tier-1 academic centers (e.g., Peking University People’s Hospital, Ruijin Hospital Shanghai Jiao Tong University). The National Medical Products Administration (NMPA) has approved daratumumab, ixazomib, and cilta-cel ahead of many peer nations, enabling earlier access to breakthrough therapies. Cost-effectiveness is enhanced through centralized procurement policies and inclusion of key agents (e.g., lenalidomide, bortezomib) in the National Reimbursement Drug List (NRDL), reducing out-of-pocket expenses by up to 70%. Furthermore, China’s robust hematopoietic stem cell transplantation infrastructure—performing over 12,000 ASCTs annually—ensures broad access to this potentially curative modality. Standardized national MM diagnosis and treatment guidelines (CSCO and Chinese Society of Hematology) promote evidence-based, equitable care across urban and provincial centers.

Recovery and long-term survivorship require structured, proactive guidance. Patients should engage in regular, low-impact physical activity (e.g., walking, tai chi) to maintain bone density and muscle strength while minimizing fracture risk. A calcium- and vitamin D–supplemented diet—avoiding excessive animal protein and sodium—is advised to mitigate hypercalcemia and renal stress. Strict adherence to prescribed maintenance therapy and scheduled MRD monitoring (via next-generation flow cytometry or sequencing of bone marrow aspirates every 3–6 months) is critical for early relapse detection. Vaccination schedules must be updated per ASCO/EBMT recommendations—avoiding live vaccines during active immunosuppression but prioritizing pneumococcal conjugate (PCV20), herpes zoster subunit (RZV), and annual influenza vaccines. Psychosocial resilience is fostered through dedicated MM patient advocacy networks (e.g., China Myeloma Foundation), telehealth-enabled symptom tracking apps, and routine screening for depression/anxiety using validated tools (PHQ-9, GAD-7). Finally, fertility preservation counseling should be offered prior to alkylator-based induction or ASCT, particularly for patients under age 45. With evolving therapeutic paradigms, median OS now exceeds 8–10 years for standard-risk MM—and approaches 15 years in select MRD-negative cohorts—underscoring the importance of lifelong, coordinated hematologic follow-up.