Patient‐specific genomic measurable residual disease markers for monitoring acute myeloid leukaemia and myeloid malignancy
Libby Huang, Louise Doculara, Luis Enriquez, Jodie Giles, Umma Habiba, Anita Y. Bahar, Tammy Law, Weronika Lesnowolska, Hannah McCalmont, Erika Ong, Laura Piras, Benjamin Schreiber, Nicola Venn, Wiebke Wessels, Yianni Bletas, Minjina Kang, Sam Yuen, Patrick Strong, Paulette Barahona, Ann‐Kristin Altekoester, Kimberly Dias, Dianne Sylvester, Marie Erasmus Wong, Renee Eslick, Luciano Dalla Pozza, Bhavna Padhye, Ashanka Beligaswatte, Chow Yee Lai, Michelle Ng, Chris Fraser, David Hughes, Seong Lin Khaw, Karen McCleary, Sophie Jessop, Manika Pal, Lucie Winkowska, Jan Zuna, Patrizia Larghero, Rolf Marschalek, Claus Meyer, Rishi S. Kotecha, Andrew S. Moore, Mark J. Cowley, Rosemary Sutton, Michelle J. Henderson, Toby N. TrahairSummary
Measurable residual disease (MRD) has improved acute lymphoblastic leukaemia (ALL) outcomes. Applying acute myeloid leukaemia (AML) MRD has been limited due to complexity identifying leukaemia‐specific targets. Current AML MRD relies on flow cytometry or ribonucleic acid (RNA)‐based quantitative polymerase chain reaction (PCR) but cannot be applied to all patients. With next‐generation or whole genome sequencing (NGS/WGS), myeloid MRD targets can be identified, suggesting that DNA‐based PCR‐MRD could be used. Genomic data including RNA‐seq, targeted NGS or WGS were used to develop patient‐specific PCR‐MRD assays, which were reported using EuroMRD guidelines. We developed PCR‐MRD assays in 97.6% patients and conducted prospective PCR‐MRD monitoring in 40 myeloid malignancy patients. Myeloid MRD reports had a similar turnaround time to ALL MRD. Myeloid MRD markers were highly sensitive with a higher proportion of myeloid malignancy patients (50%) having an MRD marker with a quantitative range of ≤5 × 10 −5 compared to ALL patients (29%). In patients with two MRD markers, there was excellent inter‐assay concordance. Serial MRD correlated with disease outcome. Two patients with isolated CNS relapse had low‐level BM involvement at extra‐medullary relapse. Myeloid malignancy PCR‐MRD should be studied prospectively in clinical trials across experienced MRD laboratories using the standardised EuroMRD guidelines.