Deep hematologic response to daratumumab without cardiac recovery in AL amyloidosis: A persistent dissociation in real-world practice

Abstract Background Daratumumab has transformed the management of AL amyloidosis by significantly improving hematologic response rates [1]. However, its real-world impact on cardiac recovery remains uncertain, particularly in advanced disease [2]. Methods We conducted a retrospective, single-center study including 9 patients diagnosed with AL amyloidosis between 2021 and 2023 at Bourges Hospital, France. Baseline evaluation included cardiac biomarkers, echocardiography (global longitudinal strain [GLS], LVEF), cardiac MRI, and Mayo Clinic staging. Induction therapy consisted of daratumumab-CyBorD in 6 patients. Hematologic and organ responses were assessed according to ISA and consensus criteria, respectively. Results Among the 9 patients (mean age 70.4 years; 7 men), 8 presented with severe cardiac involvement (median NT-proBNP: 8,154 ng/L; median troponin T: 82.7 ng/L). GLS was markedly impaired (–14% to +6%), with an apical sparing pattern in 4/5 patients. Five of the 6 patients treated with daratumumab achieved ≥PR, including 4 VGPRs. No cardiac responses were observed: biomarkers remained elevated, GLS was unchanged, and symptoms persisted. Two patients achieved renal responses. Conclusions In real-world practice, even deep hematologic responses to daratumumab do not translate into early cardiac improvement in patients with advanced cardiac AL amyloidosis. These findings highlight the critical importance of earlier diagnosis and the urgent need for therapies targeting cardiac amyloid deposits directly [3]. References Kastritis E, et al. Daratumumab-based treatment for AL amyloidosis. N Engl J Med. 2021;385(1):46-58. Muchtar E, et al. Delayed cardiac response despite hematologic response in AL amyloidosis. 2018;131(5):525-531. Merlini G, et al. Cardiac amyloidosis: the need for early diagnosis and novel treatments. Eur Heart J. 2022;43(33):3161-3173.