Clinical lymphoma, myeloma & leukemia · 2025
What is the Prognostic Relevance of Responses Less Than a CR to Initial AML Treatment?
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Rajendra Akhil, Smith Elliot, Atenafu Eshetu G, Bankar Aniket, Chan Steven, Davidson Marta, Gupta Vikas, Minden Mark D, Perusini Maria Agustina, Richard-Carpentier Guillaume, Schimmer Aaron, Schuh Andre C, Sibai Hassan, Yee Karen, Maze Dawn
Аннотация
BACKGROUND: Achievement of complete remission (CR) has long been one of the goals of acute myeloid leukemia (AML) treatment. Less stringent criteria for defining CR (sub-CR) have been developed to facilitate clinical trials and regulatory approvals. However, the clinical value of sub-CR in the context of advancements in sequencing and measurable residual disease, and non-intensive therapy is incompletely understood.
METHODS: We performed a retrospective analysis of 363 patients with AML (2019-2023) with CR or sub-CR responses. The primary objective was to determine predictors of sub-CR response.
RESULTS: CR was achieved in 227 and sub-CR in 136 patients. Receiving non-intensive chemotherapy (OR 8.80; 95% [4.25-18.20], P < .001) and having spliceosome pathway mutations (OR 3.53; [1.45-8.57], P = .005) were independent predictors for sub-CR response. Consistent with prior studies, patients achieving a sub-CR response following intensive chemotherapy had inferior survival compared to those achieving CR (median OS: not reached (CR) vs. 26 months [18-NA] (sub-CR); P = .002). On MVA, older age (HR 1.75; [1.04-2.95], P = .034) and adverse ELN risk (HR 2.55; [1.53-4.23], P = .001) was associated with inferior OS. But sub-CR response (HR 1.45; [0.91-2.33], P = .119) was not associated with inferior OS. In patients who received non-intensive treatment, there was no significant difference in EFS or OS between the CR and sub-CR populations.
CONCLUSIONS: In patients treated with intensive chemotherapy, achieving a sub-CR response appears to be reflective of poor disease biology. Whereas, in patients treated with non-intensive therapies, sub-CR responses may result from the continuous nature of the treatment and not necessarily portend an inferior outcome. The potential role of spliceosome pathway variants should be further evaluated.
METHODS: We performed a retrospective analysis of 363 patients with AML (2019-2023) with CR or sub-CR responses. The primary objective was to determine predictors of sub-CR response.
RESULTS: CR was achieved in 227 and sub-CR in 136 patients. Receiving non-intensive chemotherapy (OR 8.80; 95% [4.25-18.20], P < .001) and having spliceosome pathway mutations (OR 3.53; [1.45-8.57], P = .005) were independent predictors for sub-CR response. Consistent with prior studies, patients achieving a sub-CR response following intensive chemotherapy had inferior survival compared to those achieving CR (median OS: not reached (CR) vs. 26 months [18-NA] (sub-CR); P = .002). On MVA, older age (HR 1.75; [1.04-2.95], P = .034) and adverse ELN risk (HR 2.55; [1.53-4.23], P = .001) was associated with inferior OS. But sub-CR response (HR 1.45; [0.91-2.33], P = .119) was not associated with inferior OS. In patients who received non-intensive treatment, there was no significant difference in EFS or OS between the CR and sub-CR populations.
CONCLUSIONS: In patients treated with intensive chemotherapy, achieving a sub-CR response appears to be reflective of poor disease biology. Whereas, in patients treated with non-intensive therapies, sub-CR responses may result from the continuous nature of the treatment and not necessarily portend an inferior outcome. The potential role of spliceosome pathway variants should be further evaluated.