TY - JOUR
T1 - Cox proportional hazards deep neural network identifies peripheral blood complete remission to be at least equivalent to morphologic complete remission in predicting outcomes of patients treated with azacitidine-A prospective cohort study by the AGMT
AU - Pleyer, Lisa
AU - Vaisband, Marc
AU - Drost, Manuel
AU - Pfeilstöcker, Michael
AU - Stauder, Reinhard
AU - Heibl, Sonja
AU - Sill, Heinz
AU - Girschikofsky, Michael
AU - Stampfl-Mattersberger, Margarete
AU - Pichler, Angelika
AU - Hartmann, Bernd
AU - Petzer, Andreas
AU - Schreder, Martin
AU - Schmitt, Clemens A
AU - Vallet, Sonia
AU - Melchardt, Thomas
AU - Zebisch, Armin
AU - Pichler, Petra
AU - Zaborsky, Nadja
AU - Machherndl-Spandl, Sigrid
AU - Wolf, Dominik
AU - Keil, Felix
AU - Hasenauer, Jan
AU - Larcher-Senn, Julian
AU - Greil, Richard
N1 - Funding Information:
The Austrian Group for Medical Tumor Therapy (AGMT) is the sponsor for the Austrian Myeloid Registry (aMYELOIDr) and the Austrian Registry of Hypomethylating Agents and has received funding from Celgene/BMS, AbbVie, and Janssen Cilag. The AGMT is a non‐for‐profit organization and an academic study group. The group performed administrative and legal management as well as funding acquisition. No pharmaceutical company and no other funding source were involved in any way or had a role in the study design, data collection, data analysis, data interpretation, or writing of the report. No medical writer or editor was involved.
Publisher Copyright:
© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
PY - 2023/8/7
Y1 - 2023/8/7
N2 - The current gold standard of response assessment in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) is morphologic complete remission (CR) and CR with incomplete count recovery (CRi), both of which require an invasive BM evaluation. Outside of clinical trials, BM evaluations are only performed in ~50% of patients during follow-up, pinpointing a clinical need for response endpoints that do not necessitate BM assessments. We define and validate a new response type termed "peripheral blood complete remission" (PB-CR) that can be determined from the differential blood count and clinical parameters without necessitating a BM assessment. We compared the predictive value of PB-CR with morphologic CR/CRi in 1441 non-selected, consecutive patients diagnosed with MDS (n = 522; 36.2%), CMML (n = 132; 9.2%), or AML (n = 787; 54.6%), included within the Austrian Myeloid Registry (aMYELOIDr; NCT04438889). Time-to-event analyses were adjusted for 17 covariates remaining in the final Cox proportional hazards (CPH) model. DeepSurv, a CPH neural network model, and permutation-based feature importance were used to validate results. 1441 patients were included. Adjusted median overall survival for patients achieving PB-CR was 22.8 months (95%CI 18.9-26.2) versus 10.4 months (95%CI 9.7-11.2) for those who did not; HR = 0.366 (95%CI 0.303-0.441; p < .0001). Among patients achieving CR, those additionally achieving PB-CR had a median adjusted OS of 32.6 months (95%CI 26.2-49.2) versus 21.7 months (95%CI 16.9-27.7; HR = 0.400 [95%CI 0.190-0.844; p = .0161]) for those who did not. Our deep neural network analysis-based findings from a large, prospective cohort study indicate that BM evaluations solely for the purpose of identifying CR/CRi can be omitted.
AB - The current gold standard of response assessment in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) is morphologic complete remission (CR) and CR with incomplete count recovery (CRi), both of which require an invasive BM evaluation. Outside of clinical trials, BM evaluations are only performed in ~50% of patients during follow-up, pinpointing a clinical need for response endpoints that do not necessitate BM assessments. We define and validate a new response type termed "peripheral blood complete remission" (PB-CR) that can be determined from the differential blood count and clinical parameters without necessitating a BM assessment. We compared the predictive value of PB-CR with morphologic CR/CRi in 1441 non-selected, consecutive patients diagnosed with MDS (n = 522; 36.2%), CMML (n = 132; 9.2%), or AML (n = 787; 54.6%), included within the Austrian Myeloid Registry (aMYELOIDr; NCT04438889). Time-to-event analyses were adjusted for 17 covariates remaining in the final Cox proportional hazards (CPH) model. DeepSurv, a CPH neural network model, and permutation-based feature importance were used to validate results. 1441 patients were included. Adjusted median overall survival for patients achieving PB-CR was 22.8 months (95%CI 18.9-26.2) versus 10.4 months (95%CI 9.7-11.2) for those who did not; HR = 0.366 (95%CI 0.303-0.441; p < .0001). Among patients achieving CR, those additionally achieving PB-CR had a median adjusted OS of 32.6 months (95%CI 26.2-49.2) versus 21.7 months (95%CI 16.9-27.7; HR = 0.400 [95%CI 0.190-0.844; p = .0161]) for those who did not. Our deep neural network analysis-based findings from a large, prospective cohort study indicate that BM evaluations solely for the purpose of identifying CR/CRi can be omitted.
UR - http://www.scopus.com/inward/record.url?scp=85167348761&partnerID=8YFLogxK
U2 - 10.1002/ajh.27046
DO - 10.1002/ajh.27046
M3 - Journal article
C2 - 37548390
SN - 0361-8609
JO - American Journal of Hematology
JF - American Journal of Hematology
ER -