The Australasian Leukaemia and Lymphoma Group (ALLG) has conducted multi-centre investigator-initiated trials since 1974.
To review the history of ALLG acute myeloid leukaemia (AML) trials and their contribution to current standards of care.
Between 1982 and 2014, the ALLG conducted three single arm and three randomised studies investigating new chemotherapeutic agents and optimisation of dosing.
The phase III AMLM2 trial recruited 264 patients from 20 sites 1984–1987. The addition of etoposide to the standard cytarabine and daunorubicin combination established a new Australian standard of care. AMLM4 (1987-1991) examined the benefit of cytarabine intensification during induction, with improved remission offset by induction deaths. Substituting idarubicin for daunorubicin, AMLM7 (1995-2000) accrued 298 patients across 26 centres and defined the limits of conventional chemotherapy. The first cycle remission rate of 77% remains a benchmark for AML induction approaches. Subsequently, AMLM12 recruited 442 patients 2003-2010 and focussed on consolidation dosing. Results are pending. Advances in supportive care practices also led to substantial reductions in induction deaths (AMLM2 20-26% to AMLM12 ~5%), critical for delivering improvements in clinical outcomes.
Over more than 30 years the ALLG has carried out sequential scientifically valid multi-centre studies to answer key questions in management of AML. Outcomes have improved incrementally rather than as dramatic breakthroughs. Remarkably, current regimens still represent ongoing refinement of core AML drugs discovered 50 years ago. Trial design however, has changed from an all-comers approach to a modular design with studies increasingly tailored to the molecular biology of the disease.
Future directions include collection of quality of life and cost effectiveness outcomes. The ALLG’s achievements in AML reflect the skill, intellect and dedication of members and collaborators. The 1200+ patients who have dedicated their lives to the pursuit of improved clinical outcomes remain the ultimate heroes in this ongoing quest.