December 05, 2016 | ASH 2016, Chronic Myeloid Leukemia

News, January 04, 2017

Residual CML disease remains detectable above the level of MR4.5 in 40% to 90% of patients in spite of sustained imatinib therapy,” wrote study authors led by Philippe Rousselot, MD, PhD, of Hôpital André Mignot in Le Chesnay, France. Recent preclinical work has shown that PPAR-γ agonists such as pioglitazone can erode the CML leukaemia stem cell pool, potentially sensitising quiescent CML stem cells to imatinib.

Leukemia, November 2016; advance online publication

medwireNews: Patients with chronic myeloid leukemia (CML) who successfully discontinue imatinib treatment have a higher proportion of mature natural killer (NK) cells than those who experience early relapse, a substudy of the EURO-SKI data shows.

Outcomes of the EURO-SKI Trial and the British DESTINY Study reported at the 58th Annual Meeting of the American Society of Haematology, December 3 – 6.  Prof.Mhairi Copland, MD, PhD, of the University of Glasgow, UK, set out to study a cohort of patients with CML from the British DESTINY Study who decreased their dose of tyrosine kinase inhibitor. Prof.Copland and colleagues found that many patients with CML may be able to safely reduce side effects of tyrosine kinase inhibition by cutting their dose in half. 

Imatinib (IM) can safely be discontinued in patients with chronic myeloid leukemia (CML) who have had undetectable minimal residual disease (UMRD) for at least 2 years. We report the final results of the Stop Imatinib (STIM1) study with a long follow-up.

Researchers at centres in the US and Scotland have discovered ways to target the Leukaemic Stem Cell (LCSs). TKI therapies do not eradicate the disease in the majority of people as they do not switch off the abnormal stem cell that all CML cells develop from. In a small minority develop resistance to this class of drug. Teams on both sides of the Atlantic have been working hard to find ways to target Leukaemia Stem Cells.

ABL001 is a small molecule inhibitor of BCR-ABL, which is the same protein target of nilotinib and imatinib. Unlike the TKIs, ABL001 does not bind in the ATP domain; instead, it binds to a myristate site that causes a conformational change and switches off the kinase activity. “The advantage is that it doesn’t have effects on other kinases, unlike all of the TKIs, so it is better tolerated,” Hughes explained.

Stemming the regrowth of leukemia

David J Dorer, Ronalk K. Knickerbocker, Michele Baccarani, Jorge E. Cortes, Andreas Hochhaus, Moshe Talpaz, Frank G. Haluska

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  Ponatinib dose intensity was shown to be associated with rates of adverse events.

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  Pancreatitis, rash, and cardiac failure were most strongly associated with dose.

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  Time-to-event analyses suggest a lag between changes in dose and event risk.

Most reports on chronic myeloid leukaemia (CML) treatment with tyrosine kinase inhibitors (TKIs) focus on efficacy, particularly on molecular response and outcome. In contrast, adverse events (AEs) are often reported as infrequent, minor, tolerable and manageable, but they are increasingly important as therapy is potentially lifelong and multiple TKIs are available. For this reason, the European LeukemiaNet panel for CML management recommendations presents an exhaustive and critical summary of AEs emerging during CML treatment, to assist their understanding, management and prevention.