Limited duration of dexamethasone in newly diagnosed AL amyloidosis: impact on response, toxicity, and survival.
Systemic light chain amyloidosis (AL) is a life-threatening disease in which dexamethasone (Dex) is a core therapy but is limited by cumulative toxicity. The optimal duration of Dex, particularly in the era of daratumumab (Dara)-based regimens, is uncertain.
We retrospectively analyzed 216 newly diagnosed AL amyloidosis patients (2017-2023). Dex exposure was categorized as limited (≤3 months) or prolonged (>3 months) using restricted cubic spline-derived associations with hematologic response kinetics. Outcomes included hematologic and organ response, toxicity, and overall survival.
Median Dex duration was 5.5 months and was similar by Dara use. Overall response rates exceeded 90% at 6 months in both Dex groups. Limited Dex was associated with higher rates of early deep hematologic response (VGPR or better 77.5 vs 56.5%, p = 0.001; CR 42.2 vs 19.4%, p < 0.001), reflecting faster response kinetics, while overall response rates were similar. Among patients receiving limited Dex, Dara was associated with higher 6-month CR rates (66.7 vs 30.4%, p < 0.001) and increased likelihood of achieving CR in multivariable analysis (HR 4.38, 95% CI 2.44-7.85; p < 0.001). Organ responses were similar between groups. Dex-related toxicities increased after 6 months, and hospitalization was associated with worse survival.
Limiting Dex exposure was associated with preserved efficacy and reduced toxicity. Prolonged Dex was associated with increased toxicity without improving overall hematologic or organ outcomes, supporting limited Dex duration in frontline AL amyloidosis therapy.
We retrospectively analyzed 216 newly diagnosed AL amyloidosis patients (2017-2023). Dex exposure was categorized as limited (≤3 months) or prolonged (>3 months) using restricted cubic spline-derived associations with hematologic response kinetics. Outcomes included hematologic and organ response, toxicity, and overall survival.
Median Dex duration was 5.5 months and was similar by Dara use. Overall response rates exceeded 90% at 6 months in both Dex groups. Limited Dex was associated with higher rates of early deep hematologic response (VGPR or better 77.5 vs 56.5%, p = 0.001; CR 42.2 vs 19.4%, p < 0.001), reflecting faster response kinetics, while overall response rates were similar. Among patients receiving limited Dex, Dara was associated with higher 6-month CR rates (66.7 vs 30.4%, p < 0.001) and increased likelihood of achieving CR in multivariable analysis (HR 4.38, 95% CI 2.44-7.85; p < 0.001). Organ responses were similar between groups. Dex-related toxicities increased after 6 months, and hospitalization was associated with worse survival.
Limiting Dex exposure was associated with preserved efficacy and reduced toxicity. Prolonged Dex was associated with increased toxicity without improving overall hematologic or organ outcomes, supporting limited Dex duration in frontline AL amyloidosis therapy.
Authors
Hanna Hanna, Li Li, Brown Brown, Burney Burney, Abdallah Abdallah, Basali Basali, Valent Valent, Samaras Samaras, Anwer Anwer, Khouri Khouri, Raza Raza, Van Heeckeren Van Heeckeren, Hanna Hanna, Finet Finet, Williams Williams, Mazzoni Mazzoni
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