Researchers at the University of Glasgow’s Institute of Cancer Sciences have been awarded £3.1 million by Cancer Research UK to lead a first-of-its-kind pioneering study to help find new treatments for patients with difficult to treat CML. The trial will study whether a combination of TKI + another drug will kill stem cells in CML. It is based on groundbreaking work by the team in Glasgow led by the late Prof. Tess Holyoake which studied quiescent stem cells in CML. 

In chronic myeloid leukemia (CML) treatment response is determined by measurements of BCR-AB1L transcripts in peripheral blood by quantitative real-time PCR (qRT-PCR) and a 2–5 fold increase is considered a warning sign. The BCR-ABL1 gene is mainly expressed in myeloid cells whereas quantification of BCR-ABL1 is performed on the nucleated cell fraction of peripheral blood. Hence, leukocyte composition of the nucleated cell fraction may affect the result of BCR-ABL1 quantification.

Dasatinib's bioavailability is highly dependent on gastric pH. When proton-pump inhibitors (PPIs) are co-administered with dasatinib, absorption is significantly reduced. Cola intake at the time of drug administration has been demonstrated to lead to relevant increases in the bioavailability for other acid labile drugs during PPI treatment. This manuscript reviews the relevant literature supporting a strategy of temporarily lowering the gastric pH with a carbonated beverage at the time of drug administration.

The UK CML Patient Conference: '22/09 World CML Day' Saturday 22nd September 2018.

The event has now taken place, and video recordings of the main presentations are available on this page.

Click on the link in each agenda item to view the corresponding presentation.

AGENDA

Chronic Myeloid Leukaemia Patient Day. Saturday 22nd September 2018 'World CML Day'.

Organised by Professor Mhairi Copland on behalf of the NCRI CML Sub-Group.

Marlise R. Luskin Published online: 23 Jul 2018

As CML is now a controllable, chronic condition for most patients, focus turns to the impact of the disease and TKI treatment on quality of life. For young patients with CML, the opportunity to raise a family is a frequent goal. However, the TKIs that have dramatically improved CML outcomes are teratogenic, meaning that women with CML who want to conceive or who become pregnant must stop their TKI which may, in turn, comprise treatment of the CML.

"There are preliminary data that CML patients who maintain TFR successfully after TKI cessation have higher NK cell numbers and function compared with those who relapse off-treatment, further supporting the importance of recrudescence of effector-mediated immune surveillance for achieving sustained TFR in CML"....."When successful TKI therapy reduces the leukemic cell load, suppressor cell activity, and PD-1 expression, there is consequent reactivation of the immune effector response"

"At a median follow-up of 9 months, 60 patients were evaluable for a response at 3 months. The rates of patients achieving BCR-ABL1 transcript levels 􏰀 10% and 􏰀 1% at 3 months by the International Standard were 93% and 72%, respec- tively. The rates of complete cytogenetic response by conventional cytogenetics or fluorescence in situ hybridization at 6 and 12 months were 86% and 88%, respectively.

Authors: Moshe Talpaz MD, Giuseppe Saglio MD, Ehab Atallah MD, Philippe Rousselot MD, PhD
First published: 25 January 2018

Conclusions

Nilotinib is a second-generation TKI that has been approved for the first-line treatment of chronic-phase chronic myeloid leukemia, based on the results of a prospective randomized study of nilotinib vs imatinib (ENESTnd). Apart from this registration study, very few data are currently available on first-line nilotinib treatment. We report here the long-term, 6-year results of the first investigator-sponsored, GIMEMA multicenter phase 2, single-arm trial with nilotinib 400 mg twice daily as first-line treatment in 73 patients with cp CML

Stuart L. Goldberg, Michael Savona, Michael J. Mauro

Conclusions and Future Directions