Clinical update

Imatinib Discontinuation In Chronic Myeloid Leukemia: The IMMUNOSTIM Study

Despite leukemic stem cell persistence, patients with chronic myeloid leukaemia who achieve and maintain deep molecular responses may successfully stop the tyrosine kinase inhibitor imatinib. However, questions remain unanswered regarding the biological basis of molecular relapse after imatinib cessation. In IMMUNOSTIM, we monitored 51 patients from the French Stop IMatinib trial for peripheral blood T-cells and natural killer cells. 

Burwick, Richard M. MD, MPH; Kuo, Kelly MD; Brewer, Diana PA; Druker, Brian J. MD

BACKGROUND: Pregnant women with chronic myeloid leukemia (CML) can be treated effectively with the tyrosine-kinase inhibitor imatinib, but data regarding fetal and neonatal exposure and safety are limited.

CASE: We present a patient with newly diagnosed CML in early pregnancy. Leukapheresis and interferon-α were initiated in the second trimester with limited benefit. 

In patients with chronic myeloid leukemia (CML), longer treatment duration is associated with an increase in the odds ratio for preserving a major molecular response (MMR) six months after discontinuing tyrosine kinase inhibitor (TKI) therapy, according to recent data from a large study. In contrast, the depth of molecular response was not a predictor of molecular relapse-free survival (MRFS).

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.

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.