Abstract

The proteasome inhibitor, bortezomib, has become a backbone for the first line treatment of patients with AL amyloidosis who are not eligible for high dose melphalan and stem cell transplantation. The presence of t(11;14), seen in up to 40–60% of patients with AL amyloidosis, may be associated with poorer response when treated with bortezomib based regimens. This remains a critical distinction in light of recent evidence demonstrating favourable responses to BCL-2 inhibition with venetoclax in patients with t(11;14) in multiple myeloma. We report on 135 patients with newly diagnosed AL amyloidosis treated with a bortezomib-based regimen as first line therapy between 2013 and 2017. Treatment outcomes were compared between a cohort of patients with t(11;14) and those without the translocation. Forty-four patients had the presence of t(11;14). Five-year overall survival was 46% for those with t(11;14) and 72% in patients without this translocation (p = .026). The median haematologic event free survival was 17 months for patients with t(11;14) compared to 34 months without (p = .068). Haematologic response of VGPR or better was achieved in 41% of patients with t(11;14) vs 66% without t(11;14) (p = .012). Cardiac and renal responses to first line treatment with bortezomib-based regimens were also higher in patients without t(11;14). In conclusion, patients with AL amyloidosis and the presence of t(11;14) have inferior outcomes with respect to survival, as well as haematologic and organ responses, when treated with bortezomib-based regimens as first line therapy.

摘要

蛋白酶体抑制剂硼替佐米已成为不符合高剂量美法仑和干细胞移植条件的 AL 淀粉样变性患者一线治疗的支柱。t(11;14) 的存在，在高达 40-60% 的 AL 淀粉样变性患者中可见，当用基于硼替佐米的方案治疗时，可能与较差的反应有关。鉴于最近的证据表明 venetoclax 对 t(11;14) 多发性骨髓瘤患者对 BCL-2 抑制产生有利反应，这仍然是一个关键区别。我们报告了 135 名新诊断的 AL 淀粉样变性患者，他们在 2013 年至 2017 年间接受了基于硼替佐米的方案作为一线治疗。比较了一组 t(11;14) 患者和没有易位患者的治疗结果。44 名患者存在 t(11;14)。p  = .026）。t(11;14) 患者的中位血液学事件无生存期为 17 个月，而没有 t(11;14) 的患者为 34 个月 ( p  = .068)。有 t(11;14) 的患者中有 41% 达到了 VGPR 或更好的血液学反应，而没有 t(11;14) 的患者则为 66% ( p  = .012)。没有 t(11;14) 的患者对基于硼替佐米的方案一线治疗的心脏和肾脏反应也更高。总之，当使用基于硼替佐米的方案作为一线治疗时，患有 AL 淀粉样变性和 t(11;14) 的患者在生存以及血液学和器官反应方面的结果较差。