Department of Pharmacy, Mayo Clinic, Rochester, MN.
Loxo@Lilly, Lilly Corporate Center, Indianapolis, IN.
JCO Oncol Pract. 2024 Jun;20(6):797-807. doi: 10.1200/OP.23.00628. Epub 2024 Feb 26.
Limited evidence exists regarding methotrexate (MTX) resumption after patients with lymphoma receive glucarpidase for toxic MTX levels and acute kidney injury (AKI).
This retrospective review included adults with lymphoma treated with glucarpidase after MTX at Mayo Clinic between January 31, 2020, and October 10, 2022. Descriptive statistics summarize patient characteristics and clinical outcomes.
Of 11 patients treated with glucarpidase after MTX, seven (64%) were rechallenged with MTX. Indications for MTX rechallenge included confirmed CNS disease (n = 6, 86%) and intravascular lymphoma (n = 1, 14%). Compared with the nonrechallenged subgroup, before receiving MTX that required glucarpidase rescue, the rechallenged patients had lower median pretreatment serum creatinine (Scr; 0.7 1.2 mg/dL), and none had AKI with previous MTX doses, n = 0 (0%) versus n = 2 (50%). During the MTX dose requiring glucarpidase rescue, the rechallenged group had lower median peak Scr (1.26 3.32 mg/dL) and lower incidence of AKI stage III (n = 1 [14%] n = 3 [75%]), and none of the rechallenged patients required renal replacement therapy (RRT; n = 0 [0%] n = 1 [25%]). At the first rechallenge after glucarpidase administration, the median MTX dose reduction was 56% (range, 46%-75%), and the lowest used dose when prescribed according to each treatment protocol schedule was 1.5 g/m. Two (29%) patients experienced AKI (n = 1 stage I, n = 1 stage II) after MTX rechallenge. Zero patients required RRT, and zero required another glucarpidase administration. Six (86%) patients completed all recommended MTX doses.
In selected adults with lymphoma who required glucarpidase for toxic MTX levels after administration of high-dose MTX, resumption of MTX therapy at lower doses is safe. Patients selected for MTX resumption had experienced less severe AKI during the previous cycle compared with those not selected for MTX resumption.
在接受过黏糠酸酶治疗以降低毒性甲氨蝶呤（MTX）水平和急性肾损伤（AKI）的淋巴瘤患者中，有关黏糠酸酶治疗后重新开始 MTX 治疗的证据有限。
本回顾性研究纳入了 2020 年 1 月 31 日至 2022 年 10 月 10 日在梅奥诊所接受过黏糠酸酶治疗 MTX 中毒的淋巴瘤成人患者。描述性统计数据总结了患者特征和临床结局。
11 例 MTX 治疗后接受黏糠酸酶治疗的患者中，有 7 例（64%）重新接受了 MTX 治疗。MTX 重新治疗的指征包括确诊的中枢神经系统疾病（n=6，86%）和血管内淋巴瘤（n=1，14%）。与未重新治疗的亚组相比，在接受需要黏糠酸酶解救的 MTX 治疗之前，重新治疗的患者的血清肌酐（Scr）中位数较低（0.71.2mg/dL），且在之前的 MTX 剂量中没有 AKI，n=0（0%）vs n=2（50%）。在需要黏糠酸酶解救的 MTX 剂量期间，重新治疗组的 Scr 峰值中位数较低（1.263.32mg/dL），AKI Ⅲ期的发生率较低（n=1[14%]vs n=3[75%]），且没有重新治疗的患者需要肾脏替代治疗（RRT；n=0[0%]vs n=1[25%]）。在黏糠酸酶给药后首次重新治疗时，MTX 剂量中位数降低了 56%（范围，46%~75%），根据每个治疗方案计划规定的最低使用剂量为 1.5g/m。2 例（29%）患者在 MTX 重新治疗后出现 AKI（n=1 期 I，n=1 期 II）。无患者需要 RRT，也无患者需要再次使用黏糠酸酶。6 例（86%）患者完成了所有推荐的 MTX 剂量。
在接受高剂量 MTX 治疗后因 MTX 毒性而需要黏糠酸酶治疗的特定淋巴瘤成人患者中，以较低剂量重新开始 MTX 治疗是安全的。与未选择重新开始 MTX 治疗的患者相比，选择重新开始 MTX 治疗的患者在前一个周期中经历的 AKI 程度较轻。
