Kim Yaeni, Park Sung-Soo, Jeon Young-Woo, Yahng Seung-Ah, Shin Seung-Hwan, Min Chang-Ki
Department of Nephrology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Hematology, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Transplant Cell Ther. 2023 Jan;29(1):55.e1-55.e9. doi: 10.1016/j.jtct.2022.09.024. Epub 2022 Oct 4.
Newly diagnosed multiple myeloma (NDMM) frequently results in renal impairment (RI), and its natural course has not been fully elucidated in the era of novel agents. We aimed to identify the dynamics of renal function after autologous stem cell transplantation (ASCT) following induction treatment using a novel agent in transplantation-eligible NDMM patients with RI (estimated glomerular filtration rate [eGFR] ≤50 mL/min/1.73 m) at diagnosis. The factors associated with achieving a renal response based on the term renal benefit regardless of baseline eGFR were investigated as well. In a multicenter registry database including 1795 patients with plasma cell disorder, 140 transplantation-eligible NDMM patients who developed RI at the time of initiation of treatment for NDMM were identified. They received protocol-based treatment (PBT) consisting of induction treatment using proteasome inhibitors and/or immunomodulatory drugs followed by ASCT. MM and renal responses were evaluated using the International Myeloma Working Group response criteria. To evaluate the standardized improvement of renal function irrespective of baseline eGFR, renal benefit was defined as a sustained (for at least 3 months) increase in eGFR >15 mL/min/1.73 m. The mean patient age was 54.7 ± 7.4 years. With a mean baseline eGFR of 24.8 ± 13.9, the renal complete response (renalCR) and renal benefit rates were 49.3% and 67.9%, respectively. In a multivariable analysis, the 3 factors significantly associated with reduced likelihood of achieving both renalCR and renal benefit were age ≥55 years, light chain type NDMM, and failure to improve eGFR by 5 mL/min/1.73 m with supportive care when measured 3 days prior to induction therapy and at the initiation of chemotherapy. Hypertension and advanced eGFR also were associated with poor renalCR achievement. The mean eGFR improved until the time of ASCT and then decreased gradually over time. The mean eGFR improved significantly until 4 months post-PBT compared with each eGFR at previous time points, but this significant improvement disappeared by 5 months post-PBT. In a subgroup of patients who developed RI after undergoing ASCT (n = 55), the eGFR increased temporarily at 1 month post-ASCT; however, this improvement reverted to baseline at 2 months post-ASCT. Among another subgroup of 27 patients who were dialysis-dependent at the time of initial treatment, 18 (66.7%) were no longer dialysis-dependent after a median of 60 days. The best renal response was acquired early during the PBT period, and ASCT did not have a robust impact on the renal outcome. Patients who failed to achieve a renal benefit should be provided with the best supportive care for chronic kidney disease, and this simplified criterion for evaluating the renal response needs to be validated in larger studies before it can be recommended. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
新诊断的多发性骨髓瘤(NDMM)常导致肾功能损害(RI),在新型药物时代,其自然病程尚未完全阐明。我们旨在确定在诊断时估算肾小球滤过率(eGFR)≤50 mL/min/1.73 m²且符合移植条件的RI型NDMM患者中,使用新型药物进行诱导治疗后自体干细胞移植(ASCT)后肾功能的变化情况。同时还研究了无论基线eGFR如何,基于“肾脏获益”这一术语实现肾脏缓解的相关因素。在一个包含1795例浆细胞疾病患者的多中心注册数据库中,确定了140例在开始NDMM治疗时出现RI且符合移植条件的患者。他们接受了基于方案的治疗(PBT),包括使用蛋白酶体抑制剂和/或免疫调节药物进行诱导治疗,随后进行ASCT。采用国际骨髓瘤工作组缓解标准评估MM缓解和肾脏缓解情况。为了评估无论基线eGFR如何的肾功能标准化改善情况,将肾脏获益定义为eGFR持续(至少3个月)升高>15 mL/min/1.73 m²。患者的平均年龄为54.7±(7.4)岁。平均基线eGFR为24.8±(13.9),肾脏完全缓解(renalCR)率和肾脏获益率分别为49.3%和67.9%。在多变量分析中,与同时实现renalCR和肾脏获益可能性降低显著相关的3个因素为年龄≥55岁、轻链型NDMM以及在诱导治疗前3天和化疗开始时经支持治疗后eGFR未能提高5 mL/min/1.73 m²。高血压和eGFR处于晚期也与renalCR实现不佳相关。平均eGFR在ASCT前有所改善,随后随时间逐渐下降。与之前各时间点的eGFR相比,PBT后4个月时平均eGFR显著改善,但PBT后5个月时这种显著改善消失。在ASCT后出现RI的患者亚组(n = 55)中,ASCT后1个月时eGFR暂时升高;然而,这种改善在ASCT后2个月时恢复至基线水平。在初始治疗时依赖透析的27例患者的另一个亚组中,中位60天后,18例(66.7%)不再依赖透析。最佳肾脏缓解在PBT期间早期获得,ASCT对肾脏结局的影响不大。未实现肾脏获益的患者应接受针对慢性肾脏病的最佳支持治疗,在推荐这一简化的肾脏缓解评估标准之前,需要在更大规模的研究中进行验证。© 2022美国移植与细胞治疗学会。由爱思唯尔公司出版。