MM-295 Timing And Outcomes of Second-Line Therapy in the Era of Daratumumab-Based Frontline Therapy in Amyloidosis

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 24; pp. S544 - S545
• Main Authors: Hamid Bazarbachi, Abdul-Hamid, Bhutani, Divaya, Radhakrishnan, Jai, Mapara, Markus, Maurer, Mathew, Lentzsch, Suzanne, Chakraborty, Rajshekhar
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2024
• Subjects: amyloidosis; daratumumab; second-line; t(11;14); venetoclax; MM; t(11;14); amyloidosis; second-line; daratumumab; venetoclax
• ISSN: 2152-2650
• DOI: 10.1016/S2152-2650(24)01661-6

The ANDROMEDA trial established daratumumab with bortezomib-cyclophosphamide-dexamethasone (Dara-VCd) as the standard of care for newly diagnosed immunoglobulin light-chain amyloidosis (NDAL) with unprecedented very good partial response (VGPR) rates or better of 80%. Pre-daratumumab, one-third of patients with amyloidosis required a second line of treatment (LoT); however, outcomes are unknown in this current era. In this single-center, retrospective cohort study, we report the real-world outcomes of 100 consecutive patients with NDAL treated between January 2018 and December 2023 with up-front daratumumab-based therapy. Hematologic and organ responses were defined per standard criteria. Time-to-next-treatment (TTNT) was defined as the time from treatment initiation to subsequent therapy. Median follow-up was 22.3 months from initiation of first LoT. One-third of patients (34%) required a second LoT. Significant predictors of shorter TTNT were dFLC >18 mg/dL (HR 3.52 [1.52-8.15]; P=0.003] and BMPCs >15% (HR 2.67 [1.29-5.53]; P=0.008). Reasons for initiating second LoT were suboptimal response (n=23), hematologic relapse/progression (n=7), and MRD positivity (n=4). The most commonly used second LoT regimen was venetoclax-based in 50% of patients. Hematologic response was evaluable for 33 patients with a dFLC >2 and/or positive serum/urine immunofixation at second LoT initiation. A hematologic CR was achieved in 45.5%, low dFLC-PR in 3%, VGPR in 18.2%, PR in 3%, and NR in 30.3% of patients. Among 21 patients evaluable for cardiac response, 52.4% had a response to a second LoT. Among 6 patients evaluable for renal response, 33.3% had a response. Venetoclax-based regimens as a second LoT in patients harboring t(11;14) led to ≥VGPR of 78%, but re-treatment with daratumumab-based regimens led to ≥VGPR of 30%. One-third of patients (32.4%) required a third LoT. After a median follow-up from second LoT initiation of 18 months, median OS was not reached, and 2-year survival was 88% (95%CI, 77-100). Onethird of patients require a second LoT in the era of frontline Dara-VCd, mostly due to suboptimal hematologic response. Outcomes with subsequent LoTs remain favorable, with two-thirds achieving a ≥VGPR, mostly for t(11;14) treated with venetoclax. Prospective studies on novel agents such as BCL2 inhibitors and bispecific antibodies are needed in this setting.