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Prognostic impact of cytogenetic abnormalities detected by FISH in AL amyloidosis with daratumumab-based frontline therapy
Blood ( IF 21.0 ) Pub Date : 2024-08-30 , DOI: 10.1182/blood.2024025899 Rajshekhar Chakraborty 1 , Saurabh Zanwar 2 , Ute Hegenbart 3 , Divaya Bhutani 4 , Morie A Gertz 5 , Angela Dispenzieri 5 , Shaji K Kumar 5 , Anita D'Souza 6 , Anannya Patwari 7 , Andrew J Cowan 8 , GuiZhen Chen 8 , Paolo Milani 9 , Giovanni Palladini 10 , Vaishali Sanchorawala 11 , Geethika Bodanapu 12 , Stefan Schönland 13 , Suzanne Lentzsch 1 , Eli Muchtar 14
Blood ( IF 21.0 ) Pub Date : 2024-08-30 , DOI: 10.1182/blood.2024025899 Rajshekhar Chakraborty 1 , Saurabh Zanwar 2 , Ute Hegenbart 3 , Divaya Bhutani 4 , Morie A Gertz 5 , Angela Dispenzieri 5 , Shaji K Kumar 5 , Anita D'Souza 6 , Anannya Patwari 7 , Andrew J Cowan 8 , GuiZhen Chen 8 , Paolo Milani 9 , Giovanni Palladini 10 , Vaishali Sanchorawala 11 , Geethika Bodanapu 12 , Stefan Schönland 13 , Suzanne Lentzsch 1 , Eli Muchtar 14
Affiliation
We performed an international retrospective study on 283 patients with light chain (AL) amyloidosis to investigate the prognostic impact of cytogenetic abnormalities by fluorescence in situ hybridization, when treated with frontline daratumumab–based therapy. The cytogenetic subgroups of interest were t(11;14), gain/amp(1q) (hereafter, +1q), hyperdiploidy, deletion(13q), del(17p), and myeloma high-risk (HR) translocations (t[4;14], t[14;16], or t[14;20]). The end points of interest were rate of hematologic complete response (heme-CR), very good partial response (VGPR) or better, and hematologic event-free survival (heme-EFS). The incidence of abnormalities was as follows: t(11;14), 53.4%; deletion (13q), 28.9%; +1q, 22.3%; hyperdiploidy, 19.4%; HR translocations, 6.6%; and deletion(17p), 4.5%. The heme-CR rate by cytogenetic subgroups were as follows: t(11;14) vs no t(11;14), 45.2% vs 41.8% (P =0.597); del(13q) vs no del(13q), 46.8% vs 42.8% (P =0.594); +1q vs no +1q, 30.2% vs 47.9% (P =0.022); hyperdiploidy vs no hyperdiploidy, 39.5% vs 44.9% (P =0.541); HR translocations vs none, 45.5% vs 43.1% (P =0.877); and del(17p) vs no del(17p), 50.0% vs 42.9% (P =0.658), respectively. Similarly, +1q was the only subgroup with a significantly lower VGPR or better rate (64.2% vs 79.0%; P =0.033). At a median follow-up of 19.8 months, the median heme-EFS was 49.6 months (95% CI, 24.7-not reached [NR]), and the 2-year overall survival (OS) was 80.98% (95% CI, 75.6-85.4). The presence of +1q was significantly associated with worse heme-EFS on multivariate analysis (HR 2.06, 95% CI, 1.14-3.71; P =0.017). Notably, there was no adverse prognostic impact of t(11;14) on heme-EFS or OS. In conclusion, +1q is associated with worse outcome in the daratumumab-era. Clinical trials testing novel frontline immunotherapies should be enriched in +1q to further improve outcomes in this subgroup.
中文翻译:
FISH 在基于 daratumumab 的一线治疗中检测到的细胞遗传学异常对 AL 淀粉样变性的预后影响
我们对 283 例轻链 (AL) 淀粉样变性患者进行了一项国际回顾性研究,以研究在接受基于 daratumumab 的一线治疗时,通过荧光原位杂交进行细胞遗传学异常的预后影响。感兴趣的细胞遗传学亚组是 t(11;14)、gain/amp(1q)(以下简称 +1q)、高二倍体、缺失 (13q)、del(17p) 和骨髓瘤高危 (HR) 易位 (t[4;14],t[14;16] 或 t[14;20])。感兴趣的终点是血液学完全缓解率 (heme-CR)、非常好的部分缓解 (VGPR) 或更好以及血液学无事件生存期 (heme-EFS)。异常发生率如下: t(11;14), 53.4%;删除 (13q),28.9%;+第一季度,22.3%;超二倍体,19.4%;HR 易位,6.6%;和缺失 (17p),4.5%。细胞遗传学亚组的血红素 CR 率如下:t(11;14) 与无 t(11;14),45.2% 对 41.8% (P=0.597);del(13q) vs 无 del(13q),46.8% vs 42.8% (P=0.594);+1q vs 无 +1q,30.2% vs 47.9% (P=0.022);超二倍体与无超二倍体,39.5% 对 44.9% (P=0.541);HR 易位 vs 无易位,45.5% vs 43.1% (P=0.877);和 del(17p) 与无 del(17p),分别为 50.0% 对 42.9% (P=0.658)。同样,+1q 是唯一一个 VGPR 率显着降低或更高的亚组(64.2% 对 79.0%;P=0.033)。中位随访 19.8 个月时,中位血红素-EFS 为 49.6 个月 (95% CI,24.7-未达到 [NR]),2 年总生存期 (OS) 为 80.98% (95% CI,75.6-85.4)。在多变量分析中,+1q 的存在与较差的血红素 EFS 显著相关 (HR 2.06,95% CI,1.14-3.71;P=0.017)。值得注意的是,t(11;14) 在 heme-EFS 或 OS 上。总之,+1q 与 daratumumab 时代较差的结果相关。 测试新型一线免疫疗法的临床试验应在 +1q 中富集,以进一步改善该亚组的结局。
更新日期:2024-08-30
中文翻译:
FISH 在基于 daratumumab 的一线治疗中检测到的细胞遗传学异常对 AL 淀粉样变性的预后影响
我们对 283 例轻链 (AL) 淀粉样变性患者进行了一项国际回顾性研究,以研究在接受基于 daratumumab 的一线治疗时,通过荧光原位杂交进行细胞遗传学异常的预后影响。感兴趣的细胞遗传学亚组是 t(11;14)、gain/amp(1q)(以下简称 +1q)、高二倍体、缺失 (13q)、del(17p) 和骨髓瘤高危 (HR) 易位 (t[4;14],t[14;16] 或 t[14;20])。感兴趣的终点是血液学完全缓解率 (heme-CR)、非常好的部分缓解 (VGPR) 或更好以及血液学无事件生存期 (heme-EFS)。异常发生率如下: t(11;14), 53.4%;删除 (13q),28.9%;+第一季度,22.3%;超二倍体,19.4%;HR 易位,6.6%;和缺失 (17p),4.5%。细胞遗传学亚组的血红素 CR 率如下:t(11;14) 与无 t(11;14),45.2% 对 41.8% (P=0.597);del(13q) vs 无 del(13q),46.8% vs 42.8% (P=0.594);+1q vs 无 +1q,30.2% vs 47.9% (P=0.022);超二倍体与无超二倍体,39.5% 对 44.9% (P=0.541);HR 易位 vs 无易位,45.5% vs 43.1% (P=0.877);和 del(17p) 与无 del(17p),分别为 50.0% 对 42.9% (P=0.658)。同样,+1q 是唯一一个 VGPR 率显着降低或更高的亚组(64.2% 对 79.0%;P=0.033)。中位随访 19.8 个月时,中位血红素-EFS 为 49.6 个月 (95% CI,24.7-未达到 [NR]),2 年总生存期 (OS) 为 80.98% (95% CI,75.6-85.4)。在多变量分析中,+1q 的存在与较差的血红素 EFS 显著相关 (HR 2.06,95% CI,1.14-3.71;P=0.017)。值得注意的是,t(11;14) 在 heme-EFS 或 OS 上。总之,+1q 与 daratumumab 时代较差的结果相关。 测试新型一线免疫疗法的临床试验应在 +1q 中富集,以进一步改善该亚组的结局。