Outcomes of venetoclax-based therapy in patients with t(11;14) light chain amyloidosis after failure of daratumumab-based therapy.

IF 5.2 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Danai Dima, Michael Hughes, Mark Orland, Fauzia Ullah, Utkarsh Goel, Faiz Anwer, Shahzad Raza, Sandra Mazzoni, Divaya Bhutani, Louis Williams, Suzanne Lentzsch, Christy Samaras, Jason Valent, Rajshekhar Chakraborty, Jack Khouri
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引用次数: 0

Abstract

Background: 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.

Objective: This study aimed to evaluate the outcomes of venetoclax-based therapy in t(11;14) positive AL patients who previously failed dara.

Methods: Thirty-one patients with AL were included in this bi-institutional retrospective analysis.

Results: 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.

Conclusion: These findings are encouraging for the use of venetoclax as salvage therapy post-dara failure.

达拉单抗治疗失败后,t(11;14)轻链淀粉样变性患者接受venetoclax治疗的疗效。
背景:达拉单抗被纳入轻链(AL)淀粉样变性病的前期治疗中,这导致患者在病程早期对达拉单抗(daratumumab,dara)产生耐药性。复发或对达拉单抗治疗反应不佳的患者选择有限:本研究旨在评估曾接受达拉治疗失败的t(11;14)阳性AL患者接受基于venetoclax治疗的效果:这项双机构回顾性分析纳入了31例AL患者:结果:20例(65%)患者达拉治疗失败的原因是反应不足,7例(22%)是血液学复发,4例(13%)是血液学和器官复发。基于 Venetoclax 治疗的总体血液学应答率为 97%,≥ VGPR 为 91%。在19例可评估的心脏受累患者中,14例(74%)获得了器官反应。在13例可评估的肾脏受累患者中,6例(46%)获得了器官反应。中位随访时间为 22 个月,尚未达到中位下次治疗时间(TTNT)和总生存期(OS)。12个月和24个月的TTNT率分别为74%和56%。数据截止时,有四名患者死亡,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,其中6%是感染所致:这些研究结果对于将 Venetoclax 用作达拉失败后的挽救疗法是令人鼓舞的。
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来源期刊
Amyloid-Journal of Protein Folding Disorders
Amyloid-Journal of Protein Folding Disorders 生物-生化与分子生物学
CiteScore
10.60
自引率
10.90%
发文量
48
审稿时长
6-12 weeks
期刊介绍: Amyloid: the Journal of Protein Folding Disorders is dedicated to the study of all aspects of the protein groups and associated disorders that are classified as the amyloidoses as well as other disorders associated with abnormal protein folding. The journals major focus points are: etiology, pathogenesis, histopathology, chemical structure, nature of fibrillogenesis; whilst also publishing papers on the basic and chemical genetic aspects of many of these disorders. Amyloid is recognised as one of the leading publications on amyloid protein classifications and the associated disorders, as well as clinical studies on all aspects of amyloid related neurodegenerative diseases and major clinical studies on inherited amyloidosis, especially those related to transthyretin. The Journal also publishes book reviews, meeting reports, editorials, thesis abstracts, review articles and symposia in the various areas listed above.
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