AL Amyloidosis Patients Continue to Benefit from HDCT/ASCT Consolidation in the Daratumumab Era

<b>Background/Objectives</b>: Previous studies suggested superior outcomes for AL amyloidosis patients eligible for consolidation with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) compared to patients who did not receive these therapies. However, data are limited due to disease rarity, differing patient selection, and evolving treatment algorithms. Following the introduction of daratumumab, which improved outcomes in AL amyloidosis patients, it remains unclear whether HDCT/ASCT still confers additional benefit. <b>Methods</b>: Our retrospective, single-center study aimed to compare patients diagnosed between January 2003-December 2024 and consolidated in first remission with HDCT/ASCT vs. without HDCT/ASCT, both before and within the era of CD38-targeting daratumumab. <b>Results</b>: In our cohort of 106 AL systemic amyloidosis patients, 57 patients underwent HDCT/ASCT after induction therapy, while 49 had chemoimmunotherapy regimens alone. The two groups differed at initial diagnosis by age (<i>p</i> = 0.0028), renal function (eGFR, <i>p</i> = 0.0054), Troponin T levels (<i>p</i> < 0.0001) and NT-proBNP (<i>p</i> = 0.038). Patients treated with HDCT/ASCT had considerably better outcomes than patients without HDCT/ASCT. The median overall survival (OS) was 157 vs. 36 months (<i>p</i> < 0.0001), and median progression-free survival (PFS) was 81 vs. 24 months (<i>p</i> < 0.0001). Daratumumab was given to 45 patients (41.7%) during first line treatment, and patients were divided into additional subgroups: HDCT/ASCT ± daratumumab and chemotherapy ± daratumumab. OS and PFS were longer in patients treated with HDCT/ASCT, regardless of whether daratumumab was added to induction. The 5-year OS was 88%/86% in patients treated with HDCT with/without daratumumab and 37%/47% in the chemoimmunotherapy group with/without daratumumab (n.s.). The 5-year PFS in patients receiving HDCT was 63%/78% and in the group without HDCT/ASCT 38%/22% each with/without daratumumab. <b>Conclusions</b>: Thus, regardless of daratumumab use during induction treatment, our results strongly suggest that patients with AL amyloidosis undergoing HDCT/ASCT consolidation achieve superior PFS and OS compared with those treated with chemoimmunotherapy alone.