Abstract
Data from 1661 consecutive subjects with chronic-phase chronic myeloid leukemia (CML) receiving initial imatinib (n = 1379) or a 2nd-generation tyrosine-kinase inhibitor (2G-TKI; n = 282) were interrogated to determine whether the Sokal or European Treatment and Outcome Study for CML (EUTOS) long-term survival (ELTS) scores were more accurate responses and outcome predictors. Both scores predicted probabilities of achieving complete cytogenetic response (CCyR), major molecular response (MMR), failure- and progression-free survivals (FFS, PFS), and survival in all subjects and those receiving imatinib therapy. However, the ELTS score was a better predictor of MR4, MR4.5, and CML-related survival than the Sokal score. In subjects receiving 2G-TKI therapy, only the ELTS score accurately predicted probabilities of CCyR, MMR, MR4, FFS, and PFS. In the propensity score matching, subjects classified as intermediate risk by the ELTS score receiving a 2G-TKI had better responses (p < 0.001~0.061), FFS (p = 0.002), and PFS (p = 0.03) but not survival. Our data suggest better overall prediction accuracy for the ELTS score compared with the Sokal score in CML patients, especially those receiving 2G-TKIs. People identified as intermediate risk by the ELTS score may benefit more from initial 2G-TKI therapy in achieving surrogate endpoints but not survival, especially when a briefer interval to stopping TKI therapy is the therapy objective.
Highlights
Several risk scores have been developed to predict responses and/ or outcomes of persons with chronic-phase chronic myeloid leukemia (CML)
We found that the EUTOS long-term survival (ELTS) score was a better overall response and outcome predictor, especially in subjects receiving initial 2ndgeneration TKI (2G-TKI) therapy
Geelen et al reported that the ELTS score identified significant differences in probabilities of major molecular response (MMR), CML-related death, Leukemia and survival in subjects receiving 2G-TKIs compared with the Sokal score [11]
Summary
Several risk scores have been developed to predict responses and/ or outcomes of persons with chronic-phase chronic myeloid leukemia (CML). Few studies critically compared the Sokal and ELTS scores as predictors of cytogenetic and molecular responses and other outcomes such as failure- and progression-free survivals (FFS and PFS), especially in persons receiving 2G-TKIs recommended by some for persons with intermediate- or high-risk CML [18]. We compared prediction accuracies of the Sokal and ELTS scores on responses and outcomes in 1661 consecutive subjects with chronic-phase CML receiving imatinib or a 2G-TKI. Propensity-score matching was used to explore whether the Sokal or ELTS score was a better predictor of responses and outcomes to imatinib or 2G-TKI as 1st therapy, including all covariates tested in the univariable. SPSS 22.0 (SPSS, Chicago, IL, USA), R version 4.0.2 (R Core Team, Vienna, Austria), and GraphPad Prism 8 (GraphPad Software Inc., La Jolla, CA, USA) were used for analyses and graphing
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