Clinical update

"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

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

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.

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