Dana-Farber Cancer Institute, Boston, MA; Rabin Medical Center and Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Dana-Farber Cancer Institute, Boston, MA.
Clin Lymphoma Myeloma Leuk. 2024 Mar;24(3):133-140. doi: 10.1016/j.clml.2023.10.011. Epub 2023 Nov 23.
Philadelphia-chromosome-negative (Ph-neg) acute lymphoblastic leukemia (ALL) has historically been associated with poor outcomes in older patients due to adverse disease biology, as well as inferior tolerance of conventional chemotherapy. Fortunately, novel therapies, including inotuzumab ozogamicin, blinatumomab, and venetoclax, are now being incorporated into first-line therapy to improve efficacy and decrease toxicity of initial therapy. Inotuzumab ozogamicin, alone or in combination with low intensity chemotherapy, appears to be best suited for the induction phase of treatment due to efficacy in the setting of high tumor burden. In contrast, blinatumomab may be best suited for consolidation due to superior efficacy in setting of morphologic remission, with or without measurable residual disease (MRD). Venetoclax is being investigated in combination with chemotherapy and can be used for treatment of older adults with both B-cell and T-cell ALL. Ongoing trials incorporating inotuzumab, blinatumomab, and venetoclax demonstrate high rates of MRD-negative complete remissions with low early mortality. Long-term outcomes have been less favorable so far, with several trials reporting nonrelapse mortality during subsequent treatment. Unanswered questions remain regarding the optimal treatment of older adults with Ph-neg ALL, including central nervous system (CNS) prophylaxis, the most appropriate consolidation to minimize toxicity without compromising efficacy, and the role of transplant and cellular therapy. T-cell ALL remains an area of unmet need and effort is required to ensure that therapeutic advances benefit all populations equitably. In this manuscript, we review current data and ongoing trials regarding the treatment of older adults with Ph-neg ALL and define topics for further research.
费城染色体阴性（Ph-neg）急性淋巴细胞白血病（ALL）在老年患者中由于疾病生物学的不良以及对常规化疗的耐受性差，历史上与不良预后相关。幸运的是，新型疗法，包括伊妥珠单抗奥佐米星、blinatumomab 和 venetoclax，现在已被纳入一线治疗，以提高疗效并降低初始治疗的毒性。伊妥珠单抗奥佐米星单独使用或与低强度化疗联合使用，由于在高肿瘤负荷的情况下具有疗效，似乎最适合治疗的诱导阶段。相比之下，blinatumomab 可能最适合巩固治疗，因为在形态学缓解期，无论是否有可测量残留疾病（MRD），其疗效均较好。venetoclax 正在与化疗联合进行研究，可用于治疗 B 细胞和 T 细胞 ALL 的老年患者。正在进行的纳入伊妥珠单抗、blinatumomab 和 venetoclax 的试验显示，MRD 阴性完全缓解率高，早期死亡率低。到目前为止，长期结果不太理想，几项试验报告在随后的治疗期间出现非复发死亡率。关于 Ph-neg ALL 老年患者的最佳治疗方法，包括中枢神经系统（CNS）预防、最适当的巩固治疗以最大限度地降低毒性而不影响疗效，以及移植和细胞疗法的作用，仍存在未解决的问题。T 细胞 ALL 仍然是一个未满足的需求领域，需要努力确保治疗进展使所有人群平等受益。在本文中，我们回顾了 Ph-neg ALL 老年患者治疗的现有数据和正在进行的试验，并确定了进一步研究的主题。
