• Danai Dima, Michael Hughes, Mark Orland, Fauzia Ullah, Utkarsh Goel, Faiz Anwer, Shahzad Raza, Sandra Mazzoni, Divaya Bhutani, Louis Williams, Suzanne Lentzsch, Christy Samaras, Jason Valent, Rajshekhar Chakraborty, and Jack Khouri.
• Department of Hematology-Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA.
• Amyloid. 2024 Sep 1; 31 (3): 195201195-201.

BackgroundDaratumumab's incorporation in the upfront treatment of light chain (AL) amyloidosis has led to daratumumab (dara) refractoriness early in disease course. Patients who experience relapse or have suboptimal response to dara-based-therapy, have limited options.ObjectiveThis study aimed to evaluate the outcomes of venetoclax-based therapy in t(11;14) positive AL patients who previously failed dara.MethodsThirty-one patients with AL were included in this bi-institutional retrospective analysis.ResultsDara failure was due to inadequate response in 20 (65%) patients, haematologic relapse in 7 (22%), and both haematologic plus organ relapse in 4 (13%). Overall haematologic response rate to venetoclax-based therapy was 97%, with ≥ VGPR being 91%. Of the 19 evaluable patients with cardiac involvement, 14 (74%) achieved organ response. Of the 13 evaluable patients with renal involvement, 6 (46%) achieved organ response. With a median follow-up of 22 months, median time-to-next-treatment (TTNT) and overall survival (OS) were not reached. The 12- and 24-month TTNT rates were 74% and 56%, respectively. At data-cut-off, four patients had died, all from AL-related organ complications. The 12- and 24-month OS rates were 89% and 85%, respectively. Grade ≥3 adverse events occurred in 26% of patients, with 6% due to infections.ConclusionThese findings are encouraging for the use of venetoclax as salvage therapy post-dara failure.

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