Ollila Thomas A, Olszewski Adam J
Department of Medicine, Alpert Medical School of Brown University, Providence, RI, USA.
Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI, USA.
Cancer Manag Res. 2021 May 14;13:3935-3952. doi: 10.2147/CMAR.S267258. eCollection 2021.
Many patients with follicular (FL) or marginal zone lymphoma (MZL) are not eligible to receive immunochemotherapy due to advanced age or comorbidities. Recent innovations in the treatment of these indolent lymphomas provide options for multiple lines of chemotherapy-free management. More research is needed to determine which older patients are best served by a chemotherapy-free approach in the context of geriatric vulnerabilities. In the first line, regardless of disease burden, rituximab monotherapy can provide high rates of disease control with minimal toxicity, while judicious use of brief maintenance extends the duration of response. Radioimmunotherapy using ibritumomab tiuxetan is an effective and safe post-rituximab consolidation for older patients who have <25% bone marrow involvement. The combination of rituximab and lenalidomide, although "chemotherapy-free", does not improve tolerability over immunochemotherapy. However, studies support lower doses and shorter duration of lenalidomide exposure as a means to improve safety without materially compromising efficacy for older individuals. Extranodal MZL can often be effectively controlled with low-dose radiation therapy, and splenic MZL has excellent outcomes with rituximab monotherapy. For many patients with relapsed FL/MZL, simple retreatment with anti-CD20 antibodies will prove sufficient. Other currently available options for relapsed/refractory disease include ibritumomab tiuxetan, lenalidomide with rituximab, umbralisib as a potentially less toxic PI3K inhibitor, ibrutinib (for MZL), and tazemetostat (for FL, especially with mutation). Emerging data with novel forms of immunotherapy (antibody-drug conjugates like polatuzumab vedotin or loncastuximab tesirine; T-cell-engaging bispecific antibodies like mosunetuzumab or epcoritamab; and chimeric antigen receptor CAR T-cells like axicabtagene ciloleucel) suggest that immune-directed approaches can produce very high and potentially durable responses in FL/MZL with limited toxicities, further obviating the need for chemotherapy.
许多滤泡性淋巴瘤（FL）或边缘区淋巴瘤（MZL）患者因年龄较大或合并症而不符合接受免疫化疗的条件。这些惰性淋巴瘤治疗方面的最新创新为多线无化疗管理提供了选择。在老年患者存在脆弱性的背景下，需要更多研究来确定哪些老年患者最适合采用无化疗方法。在一线治疗中，无论疾病负担如何，利妥昔单抗单药治疗可提供高疾病控制率且毒性最小，而合理使用短期维持治疗可延长缓解持续时间。使用替伊莫单抗进行放射免疫治疗对于骨髓受累<25%的老年患者是一种有效且安全的利妥昔单抗后巩固治疗。利妥昔单抗与来那度胺的联合治疗，尽管“无化疗”，但与免疫化疗相比并未提高耐受性。然而，研究支持降低来那度胺剂量和缩短用药时间，以此作为提高安全性的手段，同时又不会对老年个体的疗效产生实质性影响。结外MZL通常可用低剂量放射治疗有效控制，脾MZL采用利妥昔单抗单药治疗效果良好。对于许多复发的FL/MZL患者，简单地再次使用抗CD20抗体治疗就足够了。复发/难治性疾病目前的其他可用选择包括替伊莫单抗、来那度胺联合利妥昔单抗、作为潜在毒性较小的PI3K抑制剂的乌布利昔布、伊布替尼（用于MZL）和他泽司他（用于FL，尤其是存在 突变的情况）。新型免疫治疗形式（如泊洛妥珠单抗或洛卡斯托珠单抗等抗体药物偶联物；如莫苏奈妥珠单抗或依泊妥单抗等T细胞接合双特异性抗体；以及如阿基仑赛等嵌合抗原受体CAR T细胞）的新数据表明，免疫导向方法可在FL/MZL中产生非常高且可能持久的反应，且毒性有限，进一步消除了化疗的必要性。
