Discussion and Results.

Molecular Responses after Switching from a Standard-Dose Twice-Daily Nilotinib Regimen to a Reduced-Dose Once-Daily Schedule in Patients with Chronic Myeloid Leukemia: A Real Life Observational Study (NILO-RED)

Delphine Rea, MD1, Jean-Michel Cayuela, PhD2*, Stephanie Dulucq, PhD3* and Gabriel Etienne, MD, PhD4*

Introduction

Over the last two decades, targeted therapies like imatinib (Gleevec®)and trastuzumab (Herceptin®)—drugs that target cancer cells by homing in on specific molecular changes seen primarily in those cells—have also cemented themselves as standard treatments for many cancers.

The antibiotic tigecycline, when used in combination with current treatment, may hold the key to eradicating chronic myeloid leukaemia (CML) cells, according to new research. ‌

The University of Glasgow led study, published today in Nature Medicine, demonstrates the effectiveness of combining tigecycline with the drug imatinib – a tyrosine kinase inhibitor (TKI) and standard first-line treatment of patients with CML.

Tessa Holyoake was a giant in the world of CML and her loss to the research community, patients and her fellow specialist clinicians is and will continue to be keenly felt. 

European Stop TKI Study (EURO-SKI), show that stopping TKI therapy is feasible and that about half of patients remain free from relapse after 2 years of follow-up.
A further analysis of patients who were taking imatinib suggests that stopping imatinib after 5.8 years is associated with a higher likelihood of molecular relapse-free survival.
The results were presented here at the American Society of Hematology (ASH) 2016 Annual Meeting (abstract 787).

Introduction:

The hallmark of chronic myeloid leukemia (CML) is the presence of Philadelphia chromosome, its resultant fusion transcript (BCR-ABL1), and fusion protein (p210). Alternate breakpoints in BCR (m-bcr, μ-bcr, and others) or ABL1 result in the expression of few rare fusion transcripts (e19a2, e1a2, e13a3, e14a3) and fusion proteins (p190, p200, p225) whose exact clinical significance remains to be determined.

Cancer cells are escape artists by nature. They can dodge drugs designed to cripple them due to one of their defining characteristics: their genetic makeup changes rapidly. Cancer cells are constantly evolving, and, given the right mutation, they’re able to evade treatment.

A Hochhaus1, T Masszi2, F J Giles3, J P Radich4, D M Ross5, M T Gómez Casares6, A Hellmann7, J Stentoft8, E Conneally9, V García-Gutiérrez10, N Gattermann11, W Wiktor-Jedrzejczak12, P D le Coutre13, B Martino14, S Saussele15, H D Menssen16, W Deng17, N Krunic18, V Bedoucha16 and G Saglio19

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.