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632 A Predictive Score for Failure-Free Survival in Persons with Chronic Myeloid Leukemia Receiving Imatinib

Program: Oral and Poster Abstracts
Type: Oral
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Progress with response prediction and TKI discontinuation
Hematology Disease Topics & Pathways:
Epidemiology, Clinical Research, Health Outcomes Research, Diseases, Myeloid Malignancies
Monday, December 13, 2021: 10:45 AM

Xiaoshuai Zhang1*, Xiaojun Huang2, Robert Peter Gale3 and Qian Jiang, MD4

1Peking University People's Hospital, Beijing, China
2Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
3Centre for Haematology Research, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom
4Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, People’s Republic of China, Beijing, China

Background Initial tyrosine kinase inhibitor (TKI) therapy strategies in persons with newly-diagnosed chronic phase chronic myeloid leukaemia (CML) include the standard dose imatinib, a 2nd generation TKI, staring with imatinib and then increasing the dose or switching to a 2nd generation TKI if the 2020 European LeukemiaNet (ELN) response landmarks are not met. Which therapy strategy is best is still uncertain. There is no predictive score for failure-free survival in this setting to help physicians choose between these alternatives.

Objective Develop and validate a predictive score for failure-free survival (FFS; FFS predictive score [FFSPS]) in persons with newly-diagnosed chronic phase CML receiving initial imatinib therapy.

Methods Data from 1321 consecutive subjects receiving initial therapy with imatinib were interrogated to identify co-variates predicting FFS with failure defined according to the 2020 ELN criteria. Cut-offs for continuous variables were determined by analyzing receiver-operator characteristic (ROC) curves, and a Cox multi-variable regression model was used to identify predictive co-variates in a training dataset (n = 880). A weighted predictive score (FFSPS) was developed and validated in 441 other subjects.

Results In the training dataset, WBC ≥ 120 × 10E+9 /L (Hazard Ratio [HR] = 1.7 [95% Confidence Interval (CI), 1.1, 2.2]), haemoglobin concentration ≤ 113.5 g/L (HR = 2.3 [1.7, 3.1]), blood basophils ≥ 11.5% (HR =1.6 [1.0, 2.3]) and EUTOS long-term survival (ELTS) risk score (intermediate-risk, HR = 1.9 [1.4, 2.6]; high-risk, HR = 3.7 [2.2, 5.0]) were significantly-associated with worse FFS and each assigned 1 point in the scoring system except ELTS high-risk which was assigned 2 points. According to the FFSPS, the training dataset were classified into 5 subgroups: the very low- (score = 0; n = 307, 35%), low- (score = 1; n = 176, 20%), intermediate- (score = 2; n = 183, 21%); high- (score = 3; n = 152, 17%) and the very high- (score ≥ 4; n = 62, 7%) risk subgroups. There were significant differences in the 7-year probabilities of FFS among the 5 subgroups (89% [84, 92%] vs. 76% [67, 83%] vs. 64% [56, 71%] vs. 52% [43, 60%] vs. 28% [17, 40%], p < 0.001, Figure A). The concordance statistic (C-statistic) based on the FFSPS was 0.75 (0.69, 0.78) in the training dataset. And in the validation dataset, 155 (35%), 88 (20%), 94 (21%), 70 (16%) and 34 (8%) subjects were classified as the very low-, low-, intermediate-, high-, and the very high-risk subgroups, among which there were significant differences in the probabilities of 7-year FFS (p < 0.001, Figure B). The C-statistic in the validation dataset was 0.74 (0.67, 0.80). Moreover, the FFSPS was also correlated with probabilities of major molecular response (MMR), MR4.0 and MR4.5, progression-free survival (PFS) and survival (all p-values < 0.001, Figure C-G).

Conclusions We describe a predictive score for FFS in persons with newly-diagnosed chronic phase CML receiving initial imatinib therapy. The score identifies persons with different probabilities of success. These data should help physicians estimate the best TKI-therapy strategy in this setting.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH