Department of Hematology-Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA.
Department of Hematology-Oncology, Columbia University, New York, NY, USA.
Amyloid. 2024 Sep;31(3):195-201. doi: 10.1080/13506129.2024.2366806. Epub 2024 Jul 2.
Daratumumab's incorporation in the upfront treatment of light chain (AL) amyloidosis has led to daratumumab (dara) refractoriness early in disease course. Patients who experience relapse or have suboptimal response to dara-based-therapy, have limited options.
This study aimed to evaluate the outcomes of venetoclax-based therapy in t(11;14) positive AL patients who previously failed dara.
Thirty-one patients with AL were included in this bi-institutional retrospective analysis.
Dara failure was due to inadequate response in 20 (65%) patients, haematologic relapse in 7 (22%), and both haematologic plus organ relapse in 4 (13%). Overall haematologic response rate to venetoclax-based therapy was 97%, with ≥ VGPR being 91%. Of the 19 evaluable patients with cardiac involvement, 14 (74%) achieved organ response. Of the 13 evaluable patients with renal involvement, 6 (46%) achieved organ response. With a median follow-up of 22 months, median time-to-next-treatment (TTNT) and overall survival (OS) were not reached. The 12- and 24-month TTNT rates were 74% and 56%, respectively. At data-cut-off, four patients had died, all from AL-related organ complications. The 12- and 24-month OS rates were 89% and 85%, respectively. Grade ≥3 adverse events occurred in 26% of patients, with 6% due to infections.
These findings are encouraging for the use of venetoclax as salvage therapy post-dara failure.
达雷妥尤单抗在轻链（AL）淀粉样变性的一线治疗中的应用导致疾病早期达雷妥尤单抗（dara）耐药。对于基于达雷妥尤单抗治疗后复发或反应不佳的患者，选择有限。
本研究旨在评估先前接受过达雷妥尤单抗治疗失败的 t(11;14)阳性 AL 患者接受 Venetoclax 治疗的结局。
对两家机构的 31 例 AL 患者进行回顾性分析。
20 例（65%）患者因治疗反应不足、7 例（22%）因血液学复发、4 例（13%）因血液学合并器官复发而导致达雷妥尤单抗治疗失败。Venetoclax 治疗的总体血液学缓解率为 97%，≥非常好的部分缓解（VGPR）率为 91%。在 19 例有心脏受累的可评估患者中，14 例（74%）达到器官缓解。在 13 例有肾脏受累的可评估患者中，6 例（46%）达到器官缓解。中位随访 22 个月时，中位无进展生存期（TTNT）和总生存期（OS）未达到。12 个月和 24 个月的 TTNT 率分别为 74%和 56%。在数据截止时，有 4 例患者死亡，均死于 AL 相关器官并发症。12 个月和 24 个月的 OS 率分别为 89%和 85%。26%的患者发生了≥3 级不良事件，6%的患者因感染而导致不良事件。
这些结果为 Venetoclax 在达雷妥尤单抗治疗失败后的挽救治疗中提供了使用依据。
Zotero 插件