A new mechanism of action against chronic myeloid leukemia

In recent years, the life of patients with chronic myeloid leukemia has really changed: today drugs are available that make their life expectancy substantially comparable to that of those who do not have the disease. Despite this, many patients are forced to change their therapy because they develop intolerance or resistance: that is, those same drugs cause too many side effects or they no longer work. And this means that the quality of life can suffer physical and psychological repercussions. Today, however, these patients have one more opportunity: asciminib, the progenitor of a new generation of drugs, the so-called STAMP inhibitors (Specifically Targeting the ABL Myristoyl Pocket), is also reimbursed in Italy.

Tyrosine kinase inhibitors

Chronic myeloid leukemia is caused by the uncontrolled proliferation of bone marrow stem cells and tyrosine kinase inhibitors (TKIs) are the drugs that have revolutionized the treatment ensuring improved survival. “Even today, however, many second-line patients develop resistance or intolerance to the therapy. In this scenario, it is important to make available new third-line therapeutic options that are effective, well tolerated and capable of guaranteeing a good quality of life”, says Fabrizio Pane, Full Professor, Federico II University of Naples, Director of the Hematology and Transplants UOC of Marrow, AOU Frederick II of Naples.

A specific mechanism

Thanks to its particular mechanism of action, asciminib is able to bind in a highly specific way to the myristoyl site on the kinase domain of BCR-ABL1. “Unlike other tyrosine kinase inhibitors, the new drug binds highly specifically to the BCR-ABL1 tyrosine kinase, the switch that turns on the disease. Therefore, it is an effective treatment with a good tolerability profile: this is a very important aspect given the risks to which patients may be exposed due to the long years of treatment and the frequent presence of other comorbidities” explains Fausto Castagnetti, Professor Associate, University of Bologna, “Seràgnoli” Institute of Hematology, IRCSS University Hospital of Bologna. Asciminib is in fact indicated for patients with chronic phase Philadelphia chromosome positive CML-CP (CP Ph+) with resistance or intolerance to at least two previous tyrosine kinase inhibitors.

Chronic myeloid leukemia, European go-ahead for a drug with a new mechanism of action

by Dario Rubino

30 August 2022

The importance of quality of life

Living long is important, but so is living well. As demonstrated by the data emerging from a survey conducted among patients at an international level, recently presented at the European congress of the Hematology Society (EHA), the main fears – which affect over 50% of the sample – concern the loss of effectiveness of treatments and the impact these may have on quality of life. Of the approximately 9,000 patients estimated to live in Italy today, the majority are over 60 years of age and may therefore have other concomitant pathologies, which is why the substantial absence of serious side effects recorded in studies and in clinical practice is very important.

“The phase I trial evaluated – for a median duration of 4 years – the effects of asciminib in heavily pre-treated patients and demonstrated its long-term safety, tolerability and efficacy. The Italian clinical experience on the use of asciminib in the compassionate use program conducted between 2019 and 2023 then highlighted the efficacy of the drug in maintaining and improving the molecular response (MR) and its good tolerability profile. Furthermore, a survey by the GIMEMA Foundation investigated the perception of Italian hematologists on the use of this new therapeutic option: 89% would use it as a third-line treatment in resistant patients and 98% consider it – precisely because of its tolerability – a drug also for the elderly” says Massimo Breccia, Associate Professor, La Sapienza University of Rome, Hematology Policlinico Umberto I.