当前临床医学血液病方向多发性骨髓瘤所有化疗药、靶向药、放射性药物、CAR-T等药物的药物结构、作用机制与治疗情况

目的 探讨亚砷酸联合环磷酰胺、沙利度胺、地塞米松(CTD)化疗方案治疗复发难治性多发性骨髓瘤(RRMM)的疗效和不良反应。 方法 回顾性分析使用亚砷酸联合CTD化疗方案治疗的32例既往多次化疗后复发或多次化疗未缓解的多发性骨髓瘤(MM)患者的临床资料,分析总体反应率(ORR)、临床获益率(CBR)、无进展生存期(PFS)、总体生存期(OS)、不良反应。 结果 32例患者全部能评价疗效,ORR 为53.1%(17/32),CBR为68.7%(22/32);15例既往接受以硼替佐米为基础的治疗后出现疾病进展的患者应用亚砷酸联合CTD方案评估疗效,ORR为53.3%(8/15),CBR为80.0%(12/15)。32例患者的中位随访时间为10(3～33)个月,至随访截止,20例存活,中位PFS、OS时间分别为6.0(95%CI 4.52～7.48)、24.0 (95%CI 17.14～30.85)个月,主要不良反应有胃肠道反应、白细胞减少、肝功能损害、手足麻木等。 结论 亚砷酸联合CTD化疗方案对于部分RRMM患者是一种较好的治疗选择,且对硼替佐米耐药的MM患者有一定疗效。

… chimeric antigen receptor T-cell (CAR-T) therapies have drastically improved outcomes for patients with relapsed or refractory multiple myeloma. While CART associated cytokine …

Nonimmune effector cell-associated neurotoxicity syndrome neurotoxicities (NINTs) are serious, atypical toxicities associated with ciltacabtagene autoleucel (cilta-cel), a US Food and Drug Administration chimeric antigen receptor T cell (CAR T cell) therapy approved for relapsed/refractory multiple myeloma (RRMM). Risk factors contributing to the development of NINTs are poorly understood. In a cohort of 109 patients with RRMM treated with cilta-cel, we identify predisposing risk factors and propose strategies to mitigate NINTs. We show that high-peak absolute lymphocyte count is a strong NINT predictor, which directly correlates with flow cytometry-based peripheral blood CAR T cell quantitation. The observed CAR lymphocytosis was polyclonal with a bias toward CD4+ CAR T cells rich in memory marker expression. We then identified CAR lymphocytosis-associated CD4+ CAR T cell populations, which exhibited increased inflammatory pathway gene expression. Last, we characterize NINT-associated CD4+ CAR T cell populations, which are potential therapeutic targets for future exploration.

Abstract The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future.

BACKGROUND: The prognosis and treatment of multiple myeloma (MM) has evolved greatly over the past decade. The development and incorporation of new agents such as immunomodulators and proteasome inhibitors into therapy has improved outcomes and is helping patients enjoy longer periods of remission. OBJECTIVES: To review current treatments for MM, including overview of drug therapy and management of adverse effects of therapy and comorbidities. Additionally, an overview of agents being studied and evaluated for use in MM and myeloma-related conditions, such as metastatic bone disease and venous thromboembolism, will be discussed. SUMMARY: Great strides have been made regarding the understanding of disease pathology in MM, leading to therapies that may be targeted to each individual, based on their unique biology of disease. Therapy is currently tailored based on patient issues and stage of disease, but may soon betailored individually based on the cytogenetic profile of a patient. Recent treatment guidelines have been published by the National Comprehensive Cancer Network which were updated with impressive results fromclinical trials involving agents such as immunomodulators and proteasome inhibitors. This guideline also provides information on the management of myeloma and treatment-related morbidities. As with the treatment of any cancer, clinicians must weigh risk versus benefit when determining the most appropriate therapy. Currently, corticosteroids, lenalidomide, thalidomide, and bortezomib are all used in patient swith MM. The use of chemotherapy, including high-dose therapy with stemcell transplant, is an important component of treatment for many patients.The use of high-dose therapy is continually being evaluated, and the issueof risk versus benefit is weighed for individual patients. Depending on the prognosis, it may be of benefit to endure the toxicity of higher doses toachieve a better overall response and achieve longer remission periods. Although stem cell transplantation is often performed in MM to improve survival and remission rates, some patients are unable to undergo transplant for a variety of reasons, including age (older than 65 years), comorbidities, and/or organ dysfunction.Newer drug therapies and combinations of therapy are being evaluated to better manage this population and patients who previously received high-dose chemotherapy and a stem-cell transplant. Additionally, the management of relapsed, or refractory, disease continues to be a challenge in treating the myeloma patient. Despite aggressive and improved treatments, most myeloma patients will eventually have resistance to therapyor relapse. Treatment strategies in these patients are also evolving. CONCLUSIONS: Major advancements in the diagnosis, staging, and treatmentof myeloma offer promise in the future for changing MM from a terminal illness into a chronic, manageable condition.

A wide variety of new therapeutic options for Multiple Myeloma (MM) have recently become available, extending progression-free and overall survival for patients in meaningful ways. However, these treatments are not curative, and patients eventually relapse, necessitating decisions on the appropriate choice of treatment(s) for the next phase of the disease. Additionally, an important subset of MM patients will prove to be refractory to the majority of the available treatments, requiring selection of effective therapies from the remaining options. Immunomodulatory agents (IMiDs), proteasome inhibitors, monoclonal antibodies, and alkylating agents are the major classes of MM therapies, with several options in each class. Patients who are refractory to one agent in a class may be responsive to a related compound or to a drug from a different class. However, rules for selection of alternative treatments in these situations are somewhat empirical and later phase clinical trials to inform those choices are ongoing. To address these issues the NCI Multiple Myeloma Steering Committee formed a relapsed/refractory working group to review optimal treatment choices, timing, and sequencing and provide recommendations. Additional issues considered include the role of salvage autologous stem cell transplantation, risk stratification, targeted approaches for genetic subsets of MM, appropriate clinical trial endpoints, and promising investigational agents. This report summarizes the deliberations of the working group and suggests potential avenues of research to improve the precision, timing, and durability of treatments for Myeloma.

Multiple myeloma (MM) presents a growing challenge in Taiwan's aging population, necessitating practical treatment strategies that integrate clinical evidence with real-world constraints. The 2026 Practice Guidelines from the Hematology Society of Taiwan offer a consensus-based framework tailored to Taiwan's healthcare system, balancing efficacy, accessibility, and reimbursement limitations. Given the scarcity of international clinical trials addressing "fixed-duration" therapy mandated by reimbursement-driven treatment cessation, these guidelines utilize a deliberative consensus process to bridge the evidence vacuum between global standards and local regulatory realities. The framework specifically addresses NHI-imposed administrative limits, while providing strategic recommendations for managing symptomatic relapse-a prerequisite for next-line therapy access. These guidelines outline diagnostic standards based on the IMWG criteria and risk stratification, offering alternative monitoring approaches when serial FISH, PET-CT, or MRD testing is unavailable. They emphasize individualized treatment, considering autologous stem cell transplantation eligibility, frailty scoring, and comorbidities. Proteasome inhibitors, immunomodulatory drugs, and monoclonal/bispecific antibodies are recommended across induction, consolidation, and relapsed/refractory settings, with specific dose adjustments for special populations. This document serves as a vital reference for oncology providers in Taiwan and regions facing similar "reimbursement cliffs," balancing high-level evidence with practical resource management.

Selinexor is a first in class selective inhibitor of nuclear export (SINE), blocks exportin 1 (XPO1), a protein transporter, that among other actions, shuttles cargo proteins such as tumor suppressor proteins (TSPs), the glucocorticoid receptor (GR), and oncoprotein messenger RNAs (mRNAs) across the nuclear membrane to cytoplasm. By blocking XPO1, selinexor facilitates nuclear preservation and activation of TSPs, and prevents mRNA translation of the oncoproteins leading to induction of apoptosis. The therapeutic value of selinexor in combination with dexamethasone has been successfully demonstrated in treating relapsed and/or refractory myeloma (RRMM), leading to the Food and Drug Administration (FDA) approval of selinexor in combination with dexamethasone in 2019 for the treatment of adult patients with RRMM who received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody (mAb) - a pentarefractory myeloma. More recently, selinexor in combination with bortezomib and dexamethasone was approved by the FDA in December 2020, based on the BOSTON study among RRMM patients who had received at least one prior line of therapy. With more available safety and efficacy data supporting the increased interval between dosing of selinexor (and lesser cumulative weekly dosing) and schedule, contrary to the originally approved dose of 160 mg per week, the supportive care guidelines needed to be revisited. The current manuscript summarizes the supportive care solutions with weekly dosing of selinexor and identifies the ideal potential patient for selinexor treatment.

… evaluation before treatment in patients with multiple myeloma. … myeloma (Table 3) [4]. The revised ISS (R-ISS) was proposed as a staging system better suited to the current treatment …