Major BCR-ABL1 Transcript Type Linked to Better Imatinib Response in CML

Study findings reported by researchers in Algeria suggest that b3a2 transcript may be tied to better responses to imatinib therapy in patients with chronic myeloid leukemia (CML; Hematol Oncol Stem Cell Ther. 2020 Sep 16. Epub ahead of print).

“In [CML], the impact of MBCR-ABL1 major transcript type on disease phenotype and response to treatment still controversial to date. This work aims to study the influence of Mb3a2 and Mb2a2 transcripts on clinico-biological parameters and the molecular response in patients with chronic phase [CML] (CP-CML) treated with Imatinib as frontline therapy,” wrote lead investigator Mourad Nachi, MD, Faculty of Medicine, Ahmed Ben Bella University of Oran, Algeria, and colleagues.

The 6-year prospective study was initiated in March 2013, and included 67 patients with newly-diagnosed CP-CML given front-line imatinib.

Data on disease characteristics were collected from all patients, and molecular typing was performed using multiplex real-time PCR and quantification of transcripts by real-time quantitative PCR.

The Kaplan-Meier method was used to estimate the cumulative incidence of deep molecular response (DMR), and parametric Log-Rank test was used to make the comparison; P ≤.05 is considered significant.

Approximately 60% of patients had b3a2 expression, 35.82% expressed b2a2, and 2.98% expressed a rare transcript of type e19a2.

At the point of diagnosis, b2a2 had a higher level of expression than b3a2 (67.92 vs 53.79%, respectively; P = .03). The investigators observed insignificant differences between the 2 transcript subgroups for rates <1% at 6 months and <0.1% at 12, 18 and 24 months.

“The two types of transcript had almost the same kinetics. Nevertheless, the absolute value of the BCR-ABL1/ABL ratio decrease was faster in the group of patients expressing b3a2, than in those expressing b2a2,” reported Dr Nachi et al.

At 18-months post imatinib therapy, patients with a b3a2 transcript had a better MMR than those with b2a2 (77% vs 50%, respectively; P = .09), but the 24-month DMR was not significantly different between the 2 groups (50% vs 32%, respectively; P = .20) and neither was the 36-month DMR (75 vs 70%, respectively; P = .54).

According to Dr Nachi and co-investigators, the cumulative probability of achieving MRD at 5 years was higher with b3a2 type, but this relationship was not deemed statistically significant.

“Patients with b3a2 transcript may be associated with a better response to Imatinib therapy,” they concluded.—Hina Porcelli