Gert J. Ossenkoppele, MD, PhD of VU University Medical Center, Amsterdam, Netherlands discusses the challenges of measurable residual disease (MRD) assessment in acute myeloid leukemia (AML). Prof. Ossenkoppele explains that a lot of experience is needed to perform a MRD assessment, i.e. experienced labs need to perform the tests. The European Leukemia Net is working on recommendations and guidelines on how to apply molecular MRD and flow cytometric MRD in order to harmonize the process.
Recorded at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany.

Michael Lübbert, MD, from the University of Freiburg Medical Center, Freiburg, Germany, discusses the treatment landscape for elderly acute myeloid leukemia (AML) patients at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. He describes the Decider trial (NCT00867672), which assessed the synergistic effects of hypomethylating agents together with all-trans retinoic acid or valproic acid. While the science behind this choice is complex, from a patient perspective the most important point is that both of these show moderate side effects alone. Prof. Lübbert explains that the aim of the trial was to combine either all-trans retinoic acid or valproic acid with hypomethylating agents to achieve better survival and better clinical results. While no benefit was seen with the addition of valproic acid, surprisingly good results were seen when hypomethylating agent therapy was combined with all-trans-retinoic acid, showing an increase in overall survival (OS) from 5 months to 8 months, which was not accompanied by increased toxicity. This will now be confirmed in a randomized placebo-controlled trial. Prof. Lübbert highlights that for elderly AML patients over 60 years of age, the determining factor in treatment choice is whether they are fit enough for chemotherapy or not. If patients are not fit enough for chemotherapy, they will be treated with hypomethylating agents, however this is not curative and resistance quickly builds up. For these patients, the goal is to increase the time to resistance without increasing toxicity. On the other hand, patients fit enough for chemotherapy are led towards a cure mediated by an allogenic stem cell transplant, and the question is which treatment is best to lead them to this transplant. Prof. Lübbert outlines the work of a consortium currently assessing whether milder treatment, such as with hypomethylating agents, is comparable to aggressive chemotherapy in leading patients to transplant.

At the American Society of Hematology (ASH) 2015 Annual Meeting, held in Orlando, FL, Naval Daver, MD, from the University of Texas MD Anderson Cancer Center, Houston, TX, provides an overview of new combination therapies involving hypomethylating agents. Dr Daver focuses on the following combinations: decitabine and vosarocin; decitabine and venetoclax (ABT-199); cytarabine and SGN-CD33A a CD33a monoclonal antibody .

Francesco Lo-Coco, MD, from the University Tor Vergata, Rome, Italy, discusses the potential of combinatorial treatment approaches for acute myeloid leukemia (AML) at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. Arsenic trioxide (ATO), which is used to treat acute promyelocytic leukemia (APL, APML), is not effective on its own in acute myeloid leukemia (AML). Prof. Lo-Coco suggests that new combinatorial approaches should be explored in other subsets of leukemia, using ATO together with new or conventional agents. He highlights the importance of collaboration in both pre-clinical and clinical studies, and points out that combinatorial approaches represent a good opportunity, as several combinations have not yet been explored.

Peter, who lives with AML, discusses talking openly with their kids about their cancer diagnoses.

Utz Krug, MD, from the Leverkusen Clinic, Leverkusen, Germany, discusses advances in acute myeloid leukemia (AML) treatment at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. He argues that of the compounds in clinical development, the most interesting advance is CPX-351, which is a liposomal formulation of cytarabine and daunorubicin. The same drugs used for standard 7+3 treatment are liposomally encapsulated, which optimizes the drug delivery and showed a benefit over classical 7+3 treatment in a Phase III trial in patient with secondary AML after myelodysplastic syndrome (MDS) or cytotoxic treatment (NCT01696084), a subgroup which exhibits a poor prognosis on classical 7+3, particularly in elderly patients. Prof. Krug explains that in frail patients, it may not be possible to give 7+3, but that hypomethylating agents (HMA) are now available, with results indicating that these may be comparable to 7+3 in elderly patients. In future, additional targeted therapies may be added to 7+3. Some classical cytotoxic agents, such as the topoisomerase II inhibitor vosaroxin, which showed promising but statistically non-significant advantages in older patients with relapses AML, may be worth testing in a first-line setting, either in addition to 7+3 or as a replacement for this standard therapy.

Andrew Wei, MBBS, PhD, FRACP, FRCPA, from the Alfred Hospital and Monash University, Melbourne, Australia, discusses his highlights from the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. He was particularly interested in a session on the complexity of acute myeloid leukemia (AML) focusing on aspects of its molecular biology, particularly clonal variation and clonal evolution. Dr Wei describes how the constantly evolving and changing clonal population means that multiple diseases need to be targeted in the same patient, which can be likened to trying to hit a moving target. Two main approaches came out of this discussion. Targeted therapy focused on a single molecule is unlikely to result in substantial long-term benefits because it only affects a small proportion of leukemia, and may allow resistance and evolution of another clone not susceptible to the drug. On the other hand, non-targeted approaches aim to modulate more fundamental processes not dependent on specific mutations and are therefore less likely to lead to drug resistance due to clonal evolution. Dr Wei concludes that it will be interesting to see which of these approaches, targeted or non-targeted, with be more successful.