ISAL 2017: Developments in acute leukemias

The International Symposium on Acute Leukemias (ISAL) 2017 was, as always, filled with data, scientific developments and debate. To capture the essence of this exciting conference, we spoke to some experts about the latest advances in acute leukemias.

An improved understanding of acute leukemias

A key theme at ISAL 2017 was an improved understanding of the complexity of acute leukemias, with a focus on clonal variation and evolution, as well as epigenetic changes. Dr Andrew Wei explained that for acute myeloid leukemia (AML), the research community is just starting to understand the complexity of this disease, arguing that “We’re not just targeting multiple diseases, but targeting multiple diseases within the same patient which are constantly evolving and changing, almost like trying to hit a moving target”.

Along with a better knowledge of the way the disease evolves, new molecular and flow cytometry methods that assess minimal residual disease (MRD) can assist in the prediction of outcomes and in informing treatment decisions. Prof. Gert Ossenkoppele explained that, by measuring the leukemic cells remaining, “It is possible to predict which patients will have a relapse”.

The best markers for MRD are still being investigated; as Dr Felicitas Thol pointed out, “When we hear about a mutation, we always ask ourselves: can we follow this mutation in remission, and is this a marker for relapse?”. While some mutations, such as NPM1 mutations, are good MRD markers, others, such as IDH mutations, showed no clear correlation with the number of blast cells, and would therefore, not be considered ideal candidates for MRD monitoring based on current knowledge.


Advances in treatment

Prof. Ralf Bargou presented data from an ongoing Phase III clinical trial in acute lymphoblastic leukemia (ALL). The trial investigated a new class of immunotherapeutic molecule, the bispecific T-cell engager (BiTE) blinatumomab, demonstrating that “Patients in the relapsed setting also benefit from treatment with blinatumomab”.

In an interview with Prof. Marion Subklewe, she stated that “[BiTEs] have already entered the clinic in acute lymphoblastic leukemia”, but the BiTE AMG 330 is being trialed for the first time in AML patients in a Phase I study.

While new approaches are being trialled in acute leukemias, Dr Marina Konopleva highlighted the potential of combining currently-available treatments such as venetoclax with other therapies: “We all know that AML is a multiclonal disease and there is probably a selection of the clones that have a high expression of one or the other protein.” She expects that in the future, treatments will need to target multiple clones.

According to Prof. Francesco Lo Coco, “We need to explore new combinatorial approaches” including arsenic in different AML subtypes, and “this is an opportunity because several combinations have not been explored yet”.

Arguably the biggest advances have been made in the treatment of elderly AML patients. As Prof. Hagop Kantarjian succinctly described it: “This has changed completely: even among the patients who cannot receive intensive chemotherapy”, opening “a new era of research in elderly AML, where low intensity therapy, together with targeted therapy and immune-oncology strategies are going to be able to cure older patients with AML at a much higher rate with very little side effects”.


The need for collaboration

Prof. Wolfgang Hiddemann, Chair of ISAL 2017, highlighted the progress made in AML treatment in the last decades, but admitted that there has not been a breakthrough: “We are still on the search to see which targets are the best to select”. He emphasized the need for collaboration: “We have to join forces. […] We need the collaboration of clinicians to enter patients into clinical trials, we need the support from basic researchers to tell us which pathways are unraveled and what we can potentially use, and we need of course the collaboration of the pharmaceutical industry.