Lineage-specific detection of residual disease predicts relapse in patients with chronic myeloid leukemia stopping therapy

Author(s): Ilaria S. Pagani^1,2; Naranie Shanmuganathan^1,2,3,4,5; Phuong Dang¹; Verity A. Saunders¹; Randall Grose¹; Chung H. Kok^1,2; Jane James¹; Molly Tolland^1,2; Jodi A. Braley⁴; Haley K. Altamura⁴; David T. Yeung^1,2,3; Susan Branford^2,4,5,6; Agnes S. M. Yong^1,2,7,8; Timothy P. Hughes^1,2,3; David M. Ross^1,2,3,5,9

Source: Blood (2023) 142 (25): 2192–2197.

Dr. Maen Hussein's Thoughts

A small number of patients in this study, but it is an interesting test to predict who can be off therapy in CML. Patients who are high risk probably should to be taken off therapy, but this gives us something to build on.

ABSTRACT

Patients with chronic myeloid leukemia who are eligible for treatment-free remission (TFR) may still relapse after tyrosine kinase inhibitor (TKI) cessation. There is a need for accurate predictors of outcome to enable patients with a favorable profile to proceed while avoiding futile attempts. Sensitive detection of residual disease in total leukocytes at treatment cessation is associated with relapse but is not highly discriminatory, likely because it is a composite measure of residual leukemia derived from different cell lineages, whereas only some lineages are relevant for relapse. We prospectively measured BCR::ABL1 DNA as a predictive yes/no binary test in 5 cellular fractions from 48 patients meeting conventional criteria for TKI discontinuation. The median BCR::ABL1 DNA level was higher in granulocytes and T cells, but not in other lineages, in patients who relapsed. Among the 40 patients undergoing their first TFR attempt, we defined 3 groups with differing relapse risk: granulocyte-positive group (100%), granulocyte-negative/T-cell–positive group (67%), and granulocyte-negative /T-cell–negative group (25%). These data show the critical importance of lineage-specific assessment of residual disease in the selection of patients who can attempt to achieve TFR with a high expectation of success and, concurrently, defer patients who have a high probability of relapse.

Author Affiliations

¹Precision Cancer Medicine Theme, Blood Cancer Program, Chronic Myeloid Leukaemia Research Group, South Australian Health and Medical Research Institute, Adelaide, SA, Australia; ²School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia; ³Department of Haematology and Bone Marrow Transplantation, Royal Adelaide Hospital, Adelaide, SA, Australia; ⁴Genetic and Molecular Pathology, SA Pathology, SA, Adelaide, Australia; ⁵Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia; ⁶Clinical & Health Sciences, University of South Australia, Adelaide, SA, Australia; ⁷Department of Haematology, Royal Perth Hospital, Perth, WA, Australia; ⁸Discipline of Pathology and Laboratory Medicine, The University of Western Australia Medical School, Perth, WA, Australia; ⁹Department of Haematology and Genetic Pathology, Flinders University and Medical Centre, Adelaide, SA, Australia

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