Tiong, Ing Soo

Wall, Meaghan

Bajel, Ashish

Kalro, Akash

Fleming, Shaun

Roberts, Andrew W

Thiagarajah, Nisha

Chua, Chong Chyn

Latimer, Maya

Yeung, David

Marlton, Paula

Johnston, Amanda

Enjeti, Anoop

Fong, Chun Yew

Cull, Gavin

Larsen, Stephen

Kennedy, Glen

Schwarer, Anthony

Kipp, David

Ramanathan, Sundra

Verner, Emma

Tiley, Campbell

Morris, Edward

Hahn, Uwe

Moore, John

Taper, John

Purtill, Duncan

Warburton, Pauline

Stevenson, William

Murphy, Nicholas

Tan, Peter

Beligaswatte, Ashanka

Mutsando, Howard

Hertzberg, Mark

Shortt, Jake

Szabo, Ferenc

Dunne, Karin

Wei, Andrew H

2024-03-25

Despite an increasing desire to use historical cohorts as "synthetic" controls for new drug evaluation, limited data exist regarding the comparability of real-world outcomes to those in clinical trials. Governmental cancer data often lacks details on treatment, response, and molecular characterization of disease sub-groups. The Australasian Leukaemia and Lymphoma Group National Blood Cancer Registry (ALLG NBCR) includes source information on morphology, cytogenetics, flow cytometry, and molecular features linked to treatment received (including transplantation), response to treatment, relapse, and survival outcome. Using data from 942 AML patients enrolled between 2012-2018, we assessed age and disease-matched control and interventional populations from published randomized trials that led to the registration of midostaurin, gemtuzumab ozogamicin, CPX-351, oral azacitidine, and venetoclax. Our analyses highlight important differences in real-world outcomes compared to clinical trial populations, including variations in anthracycline type, cytarabine intensity and scheduling during consolidation, and the frequency of allogeneic hematopoietic cell transplantation in first remission. Although real-world outcomes were comparable to some published studies, notable differences were apparent in others. If historical datasets were used to assess the impact of novel therapies, this work underscores the need to assess diverse datasets to enable geographic differences in treatment outcomes to be accounted for.

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

The Alfred Hospital, Melbourne, VIC, Australia.

Monash University, Melbourne, VIC, Australia.

Monash University, Melbourne, VIC, Australia.

Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC, Australia.

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Royal Melbourne Hospital, Parkville, VIC, Australia.

The University of Melbourne, Melbourne, VIC, Australia.

Royal Adelaide Hospital, Adelaide, SA, Australia.

The Alfred Hospital, Melbourne, VIC, Australia.

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Royal Melbourne Hospital, Parkville, VIC, Australia.

The University of Melbourne, Melbourne, VIC, Australia.

Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.

Royal Melbourne Hospital, Parkville, VIC, Australia.

The Alfred Hospital, Melbourne, VIC, Australia.

Monash University, Melbourne, VIC, Australia.

The Northern Hospital, Epping, VIC, Australia.

Canberra Hospital, Garran, ACT, Australia.

ACT Pathology, Garran, ACT, Australia.

Australian National University, Canberra, ACT, Australia.

Royal Adelaide Hospital, Adelaide, SA, Australia.

South Australian Health and Medical Research Institute, Adelaide, SA, Australia.

Princess Alexandra Hospital, Woolloongabba, QLD, Australia.

University of Queensland, Brisbane, QLD, Australia.

Westmead Hospital, Westmead, NSW, Australia.

Calvary Mater Newcastle, Waratah, NSW, Australia.

Austin Hospital, Heidelberg, VIC, Australia.

Sir Charles Gairdner Hospital, Nedlands, WA, Australia.

PathWest Laboratory Medicine, Nedlands, WA, Australia.

University of Western Australia, Perth, WA, Australia.

Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

Royal Brisbane and Women's Hospital, Herston, QLD, Australia.

Box Hill Hospital, Box Hill, VIC, Australia.

Barwon Health, Geelong, VIC, Australia.

St George Hospital, Kogarah, NSW, Australia.

Concord Hospital, Concord, NSW, Australia.

Gosford Hospital, Gosford, NSW, Australia.

University of Newcastle, Callaghan, NSW, Australia.

Townsville University Hospital, Douglas, QLD, Australia.

Royal Adelaide Hospital, Adelaide, SA, Australia.

The Queen Elizabeth Hospital, Woodville South, SA, Australia.

SA Pathology, Adelaide, SA, Australia.

St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia.

Nepean Hospital, Kingswood, NSW, Australia.

PathWest Laboratory Medicine, Nedlands, WA, Australia.

Fiona Stanley Hospital, Murdoch, WA, Australia.

Wollongong Hospital, Wollongong, NSW, Australia.

Royal North Shore Hospital, St Leonards, NSW, Australia.

Northern Clinical School, University of Sydney, Sydney, NSW, Australia.

Royal Hobart Hospital, Hobart, TAS, Australia.

Royal Perth Hospital, Perth, WA, Australia.

Royal Adelaide Hospital, Adelaide, SA, Australia.

Flinders Medical Centre, Bedford Park, SA, Australia.

Flinders University, Bedford Park, SA, Australia.

Toowoomba Hospital, Toowoomba, QLD, Australia.

Prince of Wales Hospital, Randwick, NSW, Australia.

Monash University, Melbourne, VIC, Australia.

Monash Medical Centre, Clayton, VIC, Australia.

Royal Darwin Hospital, Tiwi, NT, Australia.

Australasian Leukaemia and Lymphoma Group (ALLG), Melbourne, VIC, Australia.

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. andrew.wei@petermac.org.

Royal Melbourne Hospital, Parkville, VIC, Australia. andrew.wei@petermac.org.

The University of Melbourne, Melbourne, VIC, Australia. andrew.wei@petermac.org.

Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia. andrew.wei@petermac.org.

Blood Cancer J . 2024 Mar 26;14(1):54. doi: 10.1038/s41408-024-00996-x.

2044-5385

https://pubmed.ncbi.nlm.nih.gov/38531863/?otool=iaurydwlib

https://hdl.handle.net/10137/13287

Humans

Neoplasm Recurrence, Local

Treatment Outcome

Cytarabine

Gemtuzumab

Hematopoietic Stem Cell Transplantation

Leukemia, Myeloid, Acute

Antineoplastic Combined Chemotherapy Protocols

How comparable are patient outcomes in the "real-world" with populations studied in pivotal AML trials?

Journal Article

Publication