Pleyer Lisa, Vaisband Marc, Drost Manuel, Pfeilstöcker Michael, Stauder Reinhard, Heibl Sonja, Sill Heinz, Girschikofsky Michael, Stampfl-Mattersberger Margarete, Pichler Angelika, Hartmann Bernd, Petzer Andreas, Schreder Martin, Schmitt Clemens A, Vallet Sonia, Melchardt Thomas, Zebisch Armin, Pichler Petra, Zaborsky Nadja, Machherndl-Spandl Sigrid, Wolf Dominik, Keil Felix, Hasenauer Jan, Larcher-Senn Julian, Greil Richard
Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria.
Salzburg Cancer Research Institute (SCRI) Center for Clinical Cancer and Immunology Trials (CCCIT), Salzburg, Austria.
Am J Hematol. 2023 Nov;98(11):1685-1698. doi: 10.1002/ajh.27046. Epub 2023 Aug 7.
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.
目前，骨髓增生异常综合征（MDS）、慢性粒单核细胞白血病（CMML）和急性髓系白血病（AML）患者缓解评估的金标准是形态学完全缓解（CR）和计数未完全恢复的CR（CRi），这两者都需要进行侵入性的骨髓评估。在临床试验之外，只有约50%的患者在随访期间进行骨髓评估，这明确了临床上对无需骨髓评估的缓解终点的需求。我们定义并验证了一种新的缓解类型，称为“外周血完全缓解”（PB-CR），它可以根据血常规分类计数和临床参数来确定，而无需进行骨髓评估。我们在奥地利骨髓登记处（aMYELOIDr；NCT04438889）纳入的1441例未经选择的连续患者中，比较了PB-CR与形态学CR/CRi的预测价值，这些患者被诊断为MDS（n = 522；36.2%）、CMML（n = 132；9.2%）或AML（n = 787；54.6%）。生存时间分析针对最终Cox比例风险（CPH）模型中保留的17个协变量进行了调整。使用CPH神经网络模型DeepSurv和基于排列的特征重要性来验证结果。共纳入1441例患者。达到PB-CR的患者调整后的中位总生存期为22.8个月（95%CI 18.9 - 26.2），而未达到的患者为10.4个月（95%CI 9.7 - 11.2）；风险比（HR）= 0.366（95%CI 0.303 - 0.441；p <.0001）。在达到CR的患者中，额外达到PB-CR的患者调整后的中位总生存期为32.6个月（95%CI 26.2 - 49.2），而未达到的患者为21.7个月（95%CI 16.9 - 27.7；HR = 0.400 [95%CI 0.190 - 0.844；p = 0.0161]）。我们基于大型前瞻性队列研究的深度神经网络分析结果表明，仅为确定CR/CRi而进行的骨髓评估可以省略。
