Editor's Note: At the 2026 European Hematology Association (EHA) Annual Meeting, managing the treatment burden of multiple myeloma (MM) became a core topic. As innovative therapies such as bispecific antibodies (BsAbs) and CAR-T enter clinical practice, how to reduce patient infection risks, optimize the convenience of administration, and improve quality of life while pursuing deep remission has become a major challenge for clinicians. This meeting invited Professor Joseph Mikhael from City of Hope, Professor Maria-Victoria Mateos from the University Hospital of Salamanca, and Professor Xavier Leleu from Poitiers University Hospital to conduct an in-depth discussion on "Managing the Burden of MM Treatments." 【Expert Background】
Professor Joseph Mikhael: Professor at the Translational Genomics Research Institute (TGen), Hematologist at City of Hope, Chief Medical Officer of the International Myeloma Foundation (IMF). • Professor Maria-Victoria Mateos: Director of the Hematology Department at the University Hospital of Salamanca, Spain, Past President of the International Myeloma Society (IMS). • Professor Xavier Leleu: Director of the Hematology Department at Poitiers University Hospital, France.
01 Infection Risk Management: The “Invisible Burden” in MM Immunotherapy
Throughout the treatment journey of multiple myeloma, infection remains the leading cause of morbidity and mortality, particularly when using BsAbs targeting BCMA. Professor Maria-Victoria Mateos emphasized that, ideally, vaccinations should be completed before treatment begins. • Vaccination Strategy: Regular vaccination against Pneumococcal, Flu, and COVID-19 is recommended. Although the immune response to vaccines in MM patients may be limited, it remains a fundamental means of preventing severe infection. • Application of Supportive Care: Professor Xavier Leleu shared clinical practices from France. Studies found that after applying intravenous immunoglobulin (IVIG) replacement therapy, Cytomegalovirus (CMV) infections almost disappeared in clinical practice. Currently, clinical focus has shifted to Respiratory Syncytial Virus (RSV), Influenza virus, and Rhinovirus causing chronic non-infectious sinusitis and subsequent bacterial infections. • The Role of Caregivers: The experts collectively pointed out that vaccinating people living with patients (e.g., for Flu and COVID-19) is equally crucial to reduce the patient’s exposure risk by establishing a “household immune barrier.”
02 “People-Centered”: Bridging the Expectation Gap Between Doctors and Patients
In his keynote speech, Professor Joseph Mikhael proposed a core philosophy: “I do not treat myeloma, I treat people.” He noted that while clinicians often focus on statistical gains in Overall Survival (OS) and Progression-Free Survival (PFS), patient needs are often more specific. • Differences in Decision Preferences: A survey on BsAbs treatment decision-making showed that doctors focus most on survival extension and disease control, whereas patients prioritize quality of life, limitations due to adverse events (AEs), and logistics convenience. • Inspiration from James’ Case: The wish of James (63 years old, triple-class refractory patient) represents the voice of most MM patients—the hope for treatment in an outpatient setting that is predictable and manageable, without long-term hospitalization or frequent connection to machines, thereby maintaining independence in life. This requires future MM treatments to evolve toward outpatient care and extended administration intervals.
03 Outpatient Exploration of Bispecific Antibodies: From OPTTEC to Prophylactic Administration
To reduce the treatment burden for patients, the administration model of BsAbs is undergoing a transformation. Taking Teclistamab as an example, researchers are exploring how to transition it from inpatient administration to safe outpatient administration. • OPTTEC Study: This study evaluated the safety of Teclistamab in an outpatient setting. Through step-up dosing and the prophylactic use of Tocilizumab before the first dose, the incidence and severity of cytokine release syndrome (CRS) were significantly reduced. • CRS Prevention Strategies: Professor Xavier Leleu mentioned that the latest clinical data shows that prophylactic Tocilizumab can reduce the incidence of CRS to extremely low levels (0% in some cohorts). The successful application of this strategy removes the largest safety barrier in the early stages of BsAbs treatment, laying the foundation for a full shift to outpatient treatment, significantly reducing medical costs and the psychological burden on patients.
04 Next-Generation Innovative Drugs: The Dawn of Trispecific Antibodies and the Multi-Target Era
In response to the fatigue and resistance issues caused by long-term BsAbs administration, several new drugs demonstrated potential at this year’s EHA. • Optimization of Administration Frequency: Linvoseltamab adopted a Q4W (once every four weeks) maintenance dose regimen in its study. By reducing the number of visits, it directly alleviated the “treatment burden” for patients. • Alnuctamab (Alnu): This BCMA×CD3 BsAb achieved a 0% CRS incidence in the Arm C cohort (full outpatient administration combined with prophylactic Tocilizumab), marking a new height of safety for outpatient immunotherapy. • Trispecific Antibodies: Professor Joseph Mikhael looked forward to future innovations, such as Romatamig (a dual-target drug targeting BCMA and GPRC5D) and trispecific molecules that simultaneously bind BCMA, CD38, and CD3. o High-Affinity Binding and Fc Region Optimization: By enhancing affinity for tumor cells (BCMA/CD38) and silencing the Fc region, the goal is to maximize killing efficiency while minimizing CRS and neurotoxicity (ICANS). This “combination” strategy is expected not only to prolong remission but also to overcome resistance issues brought by single-target therapies.
05 Future Outlook: Toward “Burden-Free” Deep Remission
The meeting concluded that MM treatment is no longer just a competition of drug efficacy, but a contest of comprehensive management capabilities. • Precision Subtyping: Achieving precision treatment through genetic testing (such as BRCA, TP53, B7-H3, etc., though still exploratory in some MM studies) and molecular subtyping. • Logistics and Convenience: Transformation from inpatient to outpatient care and optimization from weekly administration to monthly administration. • The Value of Communication: Surveys show that the biggest challenge patients face in community or academic centers is “communication with the healthcare team.” Strengthening the popularization of academic frontiers to help patients understand the logic behind treatment plans can significantly improve treatment adherence.
【Expert Consensus Conclusion】
In the modern treatment landscape of multiple myeloma, we must establish a four-in-one management model of “Infection Prevention – Patient Participation – Outpatient Optimization – Technology Iteration.” The future of bispecific antibodies belongs to longer administration intervals (such as Q4W), lower toxicity (0% CRS target), and more diverse target options (such as GPRC5D, trispecific antibodies). As James hoped, the goal of treatment is not just survival, but a dignified, high-quality, and independent life.
