Molecular Outcome of Chronic Myeloid Leukemia Affected Patients Not in Deep Molecular Response: The “Others” from the Gimema Labnet Network

Introduction: CML is now managed as a chronic disease requiring both long-term treatment and close molecular monitoring in most patients. Evidence suggests that in a substantial number of patients (pts) who achieved a stable deep molecular response (DMR) TKI treatment can be safely discontinued. Therefore, treatment-free remission (TFR) is increasingly regarded as a feasible treatment goal in about 20% to 40% CML pts. Nevertheless, a proportion of pts with chronic-phase CML treated with TKIs still remain in stable major molecular remission (MR3) or less (MR2 only), do not achieve a DMR and therefore require long-term TKI therapy.

Patients and Methods: Hence, we focused our clinical attention on those CML pts not candidates for a TFR path, having achieved within 6 months, and further maintained, a stable MR3 or less (MR2) by investigating the large LabNet CML database, a network founded by GIMEMA in 2014. This network standardized and harmonized the molecular methodology among 51 laboratories distributed all over Italy for the diagnosis and the molecular residual disease monitoring.

Results: Out of 9,699 pts, 585 met study endpoints and achieved a MR2/MR3 within 6 months with a minimum follow up of 24 months. CML pts received frontline therapy as follows: 219 with IM, 133 with DAS and 233 with NIL. Within 24 months, 375 pts achieved a DMR (MR4, MR4,5), whereas 187 showed a stable MR2/MR3 response and 23 had some molecular fluctuations less than MR2. With the successive follow up > 24 months, 123 out of 187 (66%) achieved a DMR, 59/187 (32%) remained in stable molecular response and 5/187 (2.7%) lost the response. No difference was observed in achieving molecular responses by the three different TKIs. Among the MR2/MR3 cohort the median time to therapy switch was 37 months. Moreover, median observation time (OT) was 5.5 yrs for the total study group (585), 5.5 yrs for the DMR group (375), 5.4 yrs for the stable MR2/MR3 (187) and 4.8 yrs for the MR2 ones (23).

Conclusion: A MR2/MR3 stable response achieved within 24 months seems predictive of a good molecular outcome since 66% of these pts obtained a DMR in the successive follow up of 24 months of. Molecular fluctuations less than MR2, although in pts with a previous obtained MR3, might represent a reliable warning sign.