Abstract

A rapid and deep haematologic response is fundamental in order to improve outcomes of patients with AL amyloidosis. We evaluated the impact of timing and depth of haematologic response at early time points (at 1 and 3 months from the start of therapy) in 227 consecutive previously untreated AL patients, who received bortezomib-based primary therapy. After 1 month of therapy, 30.5% had ≥VGPR, 28% PR and 36% no response (NR), with 11% having iFLC <20 mg/L and 15% dFLC <10 mg/L. Deep haematologic response at 1 month (either ≥VGPR or iFLC <20 mg/L or dFLC <10 mg/L), was associated with a high organ response rate. The survival of patients with ≥VGPR was significantly better than those with PR and NR at 1-month landmark (p < .001) but this benefit was mainly driven by those with iFLC <20 mg/L. The depth of haematologic response at 1 month was significant across all Mayo stages. At 3 months, 46% of the patients had not significantly improved the depth of their response but even patients that improved their response from an iFLC ≥20 mg/L at 1 month to iFLC <20 mg/L at 3 months still had inferior outcome to those with an early deep response. Thus, in patients with AL amyloidosis, a very rapid and deep response is crucial, especially for those at high risk, targeting very low FLC levels within the first month of therapy.

摘要

快速而深入的血液学反应是改善 AL 淀粉样变性患者预后的基础。我们评估了 227 名接受过以硼替佐米为基础的主要治疗的连续 227 名先前未治疗的 AL 患者在早期时间点（治疗开始后 1 个月和 3 个月）的时间和血液学反应深度的影响。治疗 1 个月后，30.5% 的患者≥VGPR，28% 的患者为 PR，36% 的患者无反应 (NR)，11% 的患者 iFLC <20 mg/L 和 15% dFLC <10 mg/L。1 个月时的深度血液学反应（≥VGPR 或 iFLC <20 mg/L 或 dFLC <10 mg/L）与高器官反应率相关。≥VGPR 患者的生存率显着优于 PR 和 NR 患者的 1 个月里程碑（p < .001) 但这种益处主要是由 iFLC <20 mg/L 的那些驱动的。1 个月时血液学反应的深度在所有梅奥阶段都很显着。在 3 个月时，46% 的患者没有显着改善其反应深度，但即使将反应从 1 个月时的 iFLC ≥ 20 mg/L 提高到 3 个月时的 iFLC <20 mg/L 的患者仍具有较差的结果给那些早早做出深刻反应的人。因此，对于 AL 淀粉样变性患者，非常快速和深入的反应至关重要，特别是对于那些高危患者，在治疗的第一个月内针对非常低的 FLC 水平。