Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
Division of Hematopathology, Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota.
Am J Hematol. 2019 Jul;94(7):767-779. doi: 10.1002/ajh.25488. Epub 2019 May 3.
Hypomethylating agents (HMA) are currently the only FDA approved therapy for patients with chronic myelomonocytic leukemia (CMML). In the current retrospective study, we assessed response rates as adjudicated by the IWG (International Working Group) MDS (myelodysplastic syndrome) and MDS/MPN myeloproliferative neoplasm overlap syndrome response criteria, in 121 CMML patients treated with Azacitidine (AZA, n = 56) and Decitabine (DAC, n = 65). The overall response rates were 41% by the IWG MDS (AZA- 45%, DAC-39%), and 56% by the IWG MDS/MPN (AZA-56%, DAC-58%) response criteria, with CR (complete remission) rates of <20% for both agents, by both criteria. There were no significant differences in response rates between proliferative and dysplastic CMML. Moreover, 29% of CMML patients in a CR with HMA progressed to AML (blast transformation), underscoring the limited impact of these agents on disease biology. Progression after HMA response was associated with a median overall-survival (OS) of 8 months, while median OS in patients with primary HMA failure was 4 months. Lower serum LDH levels (<250 Units/L) were associated with HMA responses by both criteria; while ASXL1 and TET2 mutational status had no impact. HMA treated patients had a longer median OS (31 vs 18 months; P = .01), in comparison to those treated with conventional care regimens (excluding observation only patients), without any differences between AZA vs DAC (P = .37). In conclusion, this study highlights the inadequacies of HMA therapy in CMML, retrospectively validates the IWG MDS/MPN response criteria and underscores the need for newer, rationally derived therapies.
低甲基化药物（HMA）是目前唯一获得美国食品药品监督管理局（FDA）批准用于治疗慢性粒单核细胞白血病（CMML）的药物。在这项回顾性研究中，我们根据国际工作组（IWG）的 MDS（骨髓增生异常综合征）和 MDS/MPN 重叠综合征缓解标准，评估了 121 例接受阿扎胞苷（AZA，n=56）和地西他滨（DAC，n=65）治疗的 CMML 患者的缓解率。根据 IWG MDS 标准，总缓解率为 41%（AZA-45%，DAC-39%），根据 IWG MDS/MPN 标准，总缓解率为 56%（AZA-56%，DAC-58%），两种药物的完全缓解（CR）率均<20%。增殖性和发育不良性 CMML 之间的缓解率无显著差异。此外，HMA 治疗后达到 CR 的 29%的 CMML 患者进展为 AML（白血病转化），这突出了这些药物对疾病生物学的影响有限。HMA 缓解后进展与中位总生存期（OS）为 8 个月相关，而原发性 HMA 失败患者的中位 OS 为 4 个月。根据两种标准，较低的血清乳酸脱氢酶（LDH）水平（<250U/L）与 HMA 反应相关；而 ASXL1 和 TET2 突变状态没有影响。与接受常规治疗方案（不包括仅观察患者）的患者相比，接受 HMA 治疗的患者中位 OS 更长（31 与 18 个月；P=.01），且 AZA 与 DAC 之间无差异（P=.37）。总之，这项研究突出了 HMA 治疗在 CMML 中的不足，回顾性验证了 IWG MDS/MPN 缓解标准，并强调了需要新的、合理衍生的治疗方法。
