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636 A Predictive Score for Outcomes of Tyrosine Kinase-Inhibitor Therapy in Persons with Chronic Myeloid Leukaemia Presenting in Accelerated Phase

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:
Clinical Research, Real World Evidence
Monday, December 13, 2021: 11:45 AM

Sen Yang, MD1*, Xiaoshuai Zhang2*, Xiaojun Huang2,3,4,5,6,7,8,9,10,11,12,13,14,15, Robert Peter Gale16,17 and Qian Jiang, MD5,9,13,18,19,20,21,22,23,24,25

1Peking University Institute of Hematology, Peking University People’s Hospital, Beijing, AL, CHN
2Peking University People's Hospital, Beijing, China
3Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, China
4Collaborative Innovation Centre of Hematology, Peking University, Beijing, China
5National Clinical Research Center for Hematologic Disease, Beijing, China
6Department of Hematology, Peking University People's Hospital, Beijing, China
7Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
8Peking 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
9Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
10Peking-Tsinghua Center for Life Sciences, Beijing, China
11Peking University Institute of Hematology, Beijing, China
12Nanfang Hospital, Guangzhou, China
13Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China
14Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, China
15Peking University People’s Hospital, National Clinical Research Center for Hematologic Disease, Collaborative Innovation Center of Hematology, Beijing, China
16Haematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK, London, United Kingdom
17Centre for Haematology Research, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom
18Peking University People’s Hospital, Beijing, China
19Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, CHN
20Peking University People's Hospital, Beijing, CHN
21Peking University People's Hospital, BEIJING, CHN
22Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematology Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
23Peking 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, Beijing, China
24Peking University People’s Hospital, Peking University Institute of Hematology,National Clinical Research Center for Hematologic Disease, Beijing, China
25Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematology Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China, Beijing, China

Background Chronic myeloid leukaemia (CML) presenting in accelerated phase (AP) is uncommon and there are few data on predictive co-variates for outcomes of tyrosine kinase-inhibitor (TKI)-therapy. Moreover, it is unknown which outcomes of TKI-therapy in these persons correlate with European LeukemiaNet (ELN) definitions of warning and failure which were developed in people in chronic phase or whether imatinib and 2nd generation tyrosine kinase-inhibitors (TKIs) are equally effective.

Objective Identify co-variates correlated with outcomes of TKI-therapy in persons with CML presenting in AP diagnosed by MD Anderson or World Health Organization (WHO) criteria and develop a predictive score. Determine which outcomes correlate with ELN criteria of warning and failure. Compare outcomes of initial therapy with imatinib versus 2nd-generation TKIs.

Methods We interrogated data from 312 and 334 consecutive subjects with CML presenting in AP and receiving imatinib or a 2nd-generation TKI as initial therapy. Diagnosis of AP was based on widely-accepted MD Anderson or WHO criteria. Demographic, clinical and laboratory co-variates significantly correlated with outcomes were analyzed in a Cox multi-variable regression model. Propensity score matching was done to compare outcomes of initial therapy with imatinib versus a 2nd generation TKIs.

Results In the cohort defined by MD Anderson criteria there were 197 males (63%) with a median age of 41 years (Interquartile Range [IQR], 30 - 54 years). 106 subjects (34%) had ≥ 1 co-morbidities. Median haemoglobin concentration was 99 g/L (range, 40–176 g/L), WBC concentration, 138 x 10E+9/L (range, 3-797 x10E+9/L), platelet concentration, 450 x 10E+9/L (range, 11–4094 x10E+9/L) and percentage blood or bone marrow blasts (whichever was higher), 4% (range, 0-27%). Non-mutually exclusive criteria for classifying subjects as AP included: (1) 15-29% blasts (n = 22, 7%); (2) blood basophils ≥ 20% (n = 184, 59%); (3) platelets < 100 × 10E+9/L unrelated to therapy (n = 31, 10%); (4) clonal evolution (n = 45, 15%); (5) ≥ 2 features (n = 30, 10%). Co-variates associated with failure-free survival (FFS) were haemoglobin concentration < 100 g/L (HR = 1.9; 95% Confidence Interval [CI], 1.1, 3.1; p = 0.014) and blasts > 4.5% (HR = 1.8 [1.1 - 2.9]; p = 0.013). Co-variates associated with progression-free survival (PFS) were platelets < 230 × 10E+9/L (HR = 3.3 [1.7, 6.5]; p < 0.001), blasts > 4.5% (HR = 2.4 [1.3, 4.6]; p = 0.007) and ≥ 1 co-morbidities (HR = 2.4 [1.2, 4.7]; p = 0.010). Co-variates associated with survival were haemoglobin concentration < 100 g/L (HR = 3.3 [1.1, 10.2]; p = 0.04), platelets < 230 × 10E+9/L (HR = 11.4 [3.9, 33.3]; p < 0.001) and ≥ 1 co-morbidities (HR = 6.7 [2.3, 19.5]; p < 0.001). Next, we divided subjects into 4 cohorts: (1) low-risk (no adverse co-variate; n = 49); (2) intermediate-1 risk (1 adverse co-variate; n = 116); (3) intermediate-2 risk (2 adverse co-variates; n = 92); and (4) high-risk (≥ 3 adverse co-variates; n = 47) with significant different probabilities of FFS, PFS and survival (all p-values < 0.001). Using the 2020 ELN criteria for warning at 3 months was significantly-associated with worse FFS (HR = 3.1 [1.7, 5.7]; p < 0.001). Failure at 3 months was significantly associated with worse PFS (HR = 9.3 [4.3, 18.8]; p < 0.001) and survival (HR = 6.2 [2.0, 19.2]; p = 0.002). In propensity score matching analyses subjects receiving initial therapy with imatinib had lower probabilities of complete cytogenetic response (CCyR; HR = 1.3 [1.0, 1.8]; p = 0.079), major molecular response (MMR; HR = 1.2 [0.8, 1.7; p = 0.386) and molecular response 4.5 (.5; HR = 1.8 [1.1, 3.1]; p = 0.019). However, other endpoints including FFS, PFS and survival were similar for both interventions. Similar results in the subjects diagnosed as AP using the WHO criteria.

Conclusions We identify co-variates associated with several outcomes of TKI-therapy in persons presenting in AP CML and used these to develop a prognostic score. We show the 2020 ELN criteria for warning and failure to TKI-therapy developed in persons in chronic phase also operate in subjects diagnosed in AP. Lastly, using propensity score matching we show that whilst some landmarks are achieved more rapidly in persons initially treated with a 2nd generation TKI, FFS, PFS and survival are similar to those in persons initially treated with imatinib. Our data should help inform physicians treating person with CML presenting in AP.

Disclosures: No relevant conflicts of interest to declare.

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