The Depth Of ‘Complete’ Molecular Response Predicts Molecular Relapse In Chronic Myeloid Leukaemia Patients On Tyrosine Kinase Inhibitor Therapy

There is currently no universal definition of complete molecular response (CMR) in chronic myeloid leukaemia (CML). This has implications for studies of TKI withdrawal as CMR is the main criterion for entry into these trials. We aimed to assess the proportion of patients in our practice who achieved CMR by a variety of definitions. We hoped to identify a definition that was predictive of sustained CMR and could therefore be recommended to predict those patients who might be able to stop treatment in the longer term.

We conducted a retrospective analysis of a comprehensive CML database of serial RT-qPCR results of 215 patients achieving deep molecular responses on TKI therapy. The least stringent definition of CMR was defined as BCR-ABL1 transcripts <11 and ABL1 control value (CV)>10,000. The depth of CMR was categorised according to transcript number and CV. Probability of molecular relapse according to depth of CMR at 2 and 5 years from initial CMR (ICMR) was estimated using the Kaplan Meier method.

Patients with 6-10 transcripts (any CV) were most likely to lose CMR by 2 years (86.4%) while patients with 0 transcripts (any CV) were least likely to do so (7.6%). There was no difference in the probability of molecular relapse between patients with 1-5 transcripts (CV>32,000) and those with 0 transcripts (any CV) (RR at 2 years=1 p=0.945, RR at 5 years=3.7 p = 0.114).

Depth of CMR predicts molecular relapse at 2 and 5 years from ICMR. CMR4.5 (<6 transcripts) is the least stringent response that is required to sustain CMR. Patients with <6 transcripts (CV>32,000) are equally as likely to sustain CMR as patients with 0 transcripts up to 5 years from ICMR. These patients may be suitable for a stopping trial.

Apperley:Ariad: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Honoraria, Research Funding; Pfizer: Honoraria. Milojkovic:BMS: Honoraria; Pfizer: Honoraria; Ariad: Honoraria; Novartis: Honoraria.