决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
英文原题:Consensus Guidelines and Recommendations for the anti-CD38-based Therapy in Clinical Practice for Relapsed/Refractory Multiple Myeloma: From the Pan-Pacific Multiple Myeloma Working Group.
Consensus Guidelines and Recommendations for the anti-CD38-based Therapy in Clinical Practice for Relapsed/Refractory Multiple Myeloma: From the Pan-Pacific Multiple Myeloma Working Group.
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包括 daratumumab 和 isatuximab 在内的抗 CD38 单克隆抗体(mAb)已成为复发/难治性多发性骨髓瘤(RRMM)治疗的重要组成部分。本专家共识基于证据,为其优化应用提供指导,内容包括方案选择、老年或衰弱患者的特殊考量及高危亚组治疗。重点涵盖抗 CD38 方案选择、按衰弱程度和合并症进行患者分层、血液学毒性管理策略及再治疗考量。抗 CD38 mAb 方案已在不同 RRMM 人群中显示临床疗效,包括存在 1q21+ 等高危细胞遗传学异常的患者。耐药仍是临床挑战,尤其是既往用药患者;现有证据支持在充分洗脱期(通常 6 至 12 个月)后再次使用抗 CD38 mAb,这可能使 CD38 表达和免疫效应功能部分恢复。共识还强调,这类药物对老年或衰弱患者仍有持续价值,适当监测和支持治疗可实现持久缓解。
此外,抗 CD38 mAb 是不断演变的治疗范式中的关键组成,可用于与 CAR-T 细胞、双特异性抗体等新兴免疫疗法联合。该共识为个体化治疗决策提供框架,并指出仍需进一步研究,以优化抗 CD38 mAb 在现代 RRMM 治疗中的整合应用。
Anti-CD38 monoclonal antibodies (mAbs), including daratumumab and isatuximab, have become key components of treatment for relapsed/refractory multiple myeloma (RRMM). This expert consensus provides evidence-based guidance on their optimal use, including regimen selection, special considerations for elderly or frail patients, and the treatment of high-risk subgroups. Key topics addressed include the selection of anti-CD38-based regimens, patient stratification by frailty and comorbidities, strategies for managing hematologic toxicities, and considerations for re-treatment.
Anti-CD38 mAb-based regimens have demonstrated clinical efficacy across diverse RRMM populations, including patients with high-risk cytogenetic abnormalities such as 1q21+. While resistance remains a clinical challenge, particularly in previously exposed patients, current evidence supports the feasibility of anti-CD38 mAb rechallenge following a substantial washout period (typically 6 to 12 months), which may allow partial recovery of CD38 expression and immune effector function.
The consensus also emphasizes the continued utility of these agents in elderly or frail individuals, where durable responses can be achieved with appropriate monitoring and supportive care.
Moreover, anti-CD38 mAbs are recognized as key components within evolving treatment paradigms, supporting their use for combination strategies involving emerging immunotherapies such as CAR-T cells and bispecific antibodies. This consensus provides a framework to guide individualized treatment decisions and highlights the need for continued research to optimize the integration of anti-CD38 mAbs into the modern therapeutic landscape of RRMM.
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