From research to personalised treatments: this is how we manage the condition today

At the time, British newspapers reported for the first time on an anti-leukaemia pill. We are talking about a few decades ago when, alongside bone marrow transplants from donors or autologous transplants, a new treatment emerged that was capable of ‘combating’ the genetic root cause of chronic myeloid leukaemia. This is a cancer of the bone marrow stem cells and is characterised by the presence of the Philadelphia (Ph) chromosome, which leads to the formation of the BCR-ABL1 fusion gene – the starting point for the uncontrolled proliferation of myeloid cells.

In Italia, there are around 9,000 patients suffering from this rare blood cancer (75 per cent of whom are undergoing first-line treatment). But let’s get back to the story. The oral drug was known by the code name STI-571. “It is the first therapy to act directly on an enzyme produced exclusively by the diseased cells, which enables them to multiply and become increasingly stronger,” explained Brian Drucker of the University of Oregon at the time, as reported by b –“. The great breakthrough had stemmed from a laboratory observation. Leukaemia cells carry the Philadelphia chromosome in their genetic makeup, to the extent that forms of the disease in which this genetic alteration is present are termed ‘Philadelphia-positive’. However, the alteration characteristic of this disease does not merely alter the genetic structure of the chromosome. A closer examination of the DNA sequence revealed that, in the altered cells, two genes come very close together, almost ‘touching’ one another rather than remaining distant as they do in healthy cells. This results in the formation of a hybrid which, in effect, acts as a ‘new’ gene, because this structure triggers the production of a specific enzyme. This enzyme acts as a ‘driver’ for the development and proliferation of diseased cells, giving them the ability to multiply at the expense of healthy cells. “STI-571 directly inhibits this enzyme in chronic myeloid leukaemia,” added Drucker, noting that this discovery had paved the way for a new approach in haematological oncology.

Much has changed since those statements were made. And the treatment of chronic myeloid leukaemia has become something of a ‘case history’ in haematology, given the extent to which targeted drugs have transformed not only life expectancy but also quality of life in a vast number of patients, to the extent that stem cell transplants are now restricted to selected cases. The revolution brought about by STI-571 can now be understood in the context of the so-called tyrosine kinase inhibitors (TKIs): thanks to these oral therapies, which block the specific action of the abnormal protein and thus prevent the proliferation of leukaemia cells. Starting with the pioneer drug imatinib, we have gradually moved over the years to a series of different medicines, culminating in the most recent one, asciminib. Generally, these drugs keep the disease under control, achieving what is known as a deep molecular response in a high percentage of patients. Furthermore, when a medicine becomes less effective or is not well tolerated, it is possible to switch to a next-generation TKI, including third-generation TKIs such as asciminib or ponatinib.

But there is more: in some cases, amongst a certain group of patients who maintain a deep molecular response for prolonged periods, one might even consider the controlled suspension of treatment – naturally, under the supervision of a specialist who monitors the situation over time. For many patients, there is in fact the possibility of keeping the disease in remission without medication. For those whose disease ‘flares up’ again, however, treatment can be resumed without any problems. “Thanks to these treatments, we have therefore achieved a significant increase in survival rates, to the extent that we can often say that chronic myeloid leukaemia may not be the cause of death in patients,” emphasises Maurizio Miglino of the Haematology Clinic at the University of Genoa. Before the advent of these drugs at the end of the last century, all patients who had not undergone a transplant had an average survival of three to five years. Today, we are seeing a considerable increase in life expectancy, amounting to more than 90 per cent compared with around 10 per cent at that time, across all patients, including those who have undergone a transplant.”

Of course, research does not stop because there are still goals to be achieved. This is demonstrated, amongst other things, by the results of the ASC4FIRST study, presented at the 2026 Annual Meeting of the American Society of Clinical Oncology, which show that, in the long term, a drug (asciminib) offers progressively better molecular responses at week 144 compared with established tyrosine kinase inhibitors (TKIs). In short, treatment options are expanding, including those designed to accelerate responses. “In the treatment of chronic myeloid leukaemia, the early stages of therapy are crucial for the course of the disease,” commented Massimo Breccia, Associate Professor of Haematology at the “Sapienza” University of Rome. Achieving rapid and deep molecular responses right from the start is essential for reducing the risk of progression and improving long-term outcomes. However, a significant proportion of patients still do not achieve optimal results in the early stages, with possible implications for disease control. This is why it is increasingly important to have highly effective treatment options available right from the outset.” Moreover, alongside efficacy, the issue of tolerability is emerging as a key factor in ensuring treatment continuity and maximising the benefits of treatment over time.