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Ferrata Storti Foundation
Haematologica 2019 Volume 104(11):2206-2214
Chronic Myeloid Leukemia
MR4 sustained for 12 months is associated with stable deep molecular responses in chronic myeloid leukemia
Simone Claudiani,1,2 Aoife Gatenby,2 Richard Szydlo,2 George Nesr,1,2
Adi Shacham Abulafia,3 Renuka Palanicawandar,1 Georgios Nteliopoulos,2 Jamshid Khorashad,2 Letizia Foroni,2 Jane F. Apperley1,2
and Dragana Milojkovic1
1Department of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK; 2Centre for Haematology, Imperial College London, London, UK; 3Institute of Hematology, Davidoff Cancer Centre, Beilinson Hospital, Rabin Medical Centre, Petah-Tiqva, Israel
ABSTRACT
The majority of patients with newly diagnosed chronic myeloid leukemia (CML) will enjoy a life expectancy equivalent to that of unaffected individuals, but will remain on life-long treatment with a concomitant requirement for on-going hospital interactions for molec- ular monitoring and drug dispensing. In order to determine more accu- rately the frequency of monitoring required, we performed a ‘real-life’ retrospective single-center cohort study of 450 patients with CML in at least major molecular remission (MR3) to analyze the risk of loss of MR3 [defined as at least 2 consecutive real-time quantitative polymerase chain reaction (RT-qPCR) results >0.1% International Scale (IS)]. Patients who achieved sustained MR4 (sMR4, BCR-ABL1 RT-qPCR <0.01% IS for 12 months) had a probability of loss of MR3 at 1 and 5 years of 0 and 2.6% (95%CI: 1.2-5.4) respectively, compared to 4.4% (95%CI: 1.9-9.8) and 25.4% (95%CI: 16.7-36.7) respectively, in those who achieved sustained MR3 (sMR3) but not sMR4 (P<0.001). No patient who improved their response to a deep molecular level (at least MR4) lost MR3 if they were considered compliant, had no history of resistance and remained on stan- dard dose tyrosine kinase inhibitor (TKI). MR4 maintained for at least one year represents a secure response threshold for patients with CML, after which no MR3 loss occurs if certain conditions are satisfied (stan- dard TKI dose, full compliance, and lack of previous TKI resistance). This finding may justify reduction of the frequency of hospital interaction, with an associated positive impact on quality of life, survivorship, and economic burden to both patients and healthcare providers.
Introduction
Since the advent of tyrosine kinase inhibitors (TKI), chronic myeloid leukemia (CML) has indeed become a ‘chronic’ disorder. With a life expectancy comparable to unaffected individuals,1,2 management of CML typically involves daily oral TKI, together with regular hospital attendances for molecular monitoring, control of side effects and dispensing of prescription medicines. Whilst this dramatic change is a welcome testament to the power of molecularly targeted agents, further thought can now be given to decreasing the number of interactions between patient and healthcare professionals in order to restore patient autonomy and reduce the finan- cial burden of long-term care.
In the first year of treatment, molecular monitoring at a minimum of 3-monthly intervals is recommended to assess response against international guidelines [European LeukemiaNet (ELN), National Comprehensive Cancer Network (NCCN].3,4 Several studies have shown the importance of early molecular responses (EMR) at 3, 6 and 12 months for their ability to predict the probability of achieve- ment of deep molecular responses, progression-free survival (PFS) and overall sur-
Correspondence:
SIMONE CLAUDIANI
simone.claudiani@nhs.net
Received: December 16, 2018. Accepted: March 21, 2019. Pre-published: March 28, 2019.
doi:10.3324/haematol.2018.214809
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/11/2206
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haematologica | 2019; 104(11)
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