Impact of BCR-ABL1 Transcript Type on Response, Treatment-Free Remission Rate and Survival in Chronic Myeloid Leukemia Patients Treated with Imatinib

Abstract

The most frequent BCR-ABL1-p210 transcripts in chronic myeloid leukemia (CML) are e14a2 and e13a2. Imatinib (IM) is the most common first-line tyrosine–kinase inhibitor (TKI) used to treat CML. Some studies suggest that BCR-ABL1 transcript types confer different responses to IM. The objective of this study was to correlate the expression of e14a2 or e13a2 to clinical characteristics, cumulative cytogenetic and molecular responses to IM, acquisition of deep molecular response (DMR) and its duration (sDMR), progression rate (CIP), overall survival (OS), and treatment-free remission (TFR) rate. We studied 202 CML patients, 76 expressing the e13a2 and 126 the e14a2, and correlated the differential transcript expression with the above-mentioned parameters. There were no differences in the cumulative incidence of cytogenetic responses nor in the acquisition of DMR and sDMR between the two groups, but the e14a2 transcript had a positive impact on molecular response during the first 6 months, whereas the e13a2 was associated with improved long-term OS. No correlation was observed between the transcript type and TFR rate.

Impact of BCR-ABL1 Transcript Type on Outcome in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors: A Pairwise and Bayesian Network Meta-Analysis

“…A total of 8 studies involving 2,880 patients were included in this part. Of these, DMR is defined as MR 4 in 4 studies (10,12,15,19), MR 4.5 in 3 studies (13,16,18), and MR 4 /MR 4.5 in 1 study (11). Compared to e13a2, the patients with e14a2 transcripts had a favorable effect on DMR at 6, 12, 18 and 60 months, with an OR of 2.13 (95% CI: 1.19-3.80, I 2 = 35.83%, 7 studies), 2.00 (95% CI: 1.36-2.95, I 2 = 44.64%, 8 studies), 1.84 (95% CI: 1.40-2.41, I 2 = 35.45%, 8 studies) and 2.21 (95% CI: 1.71-2.87, I 2 = 42.62%, 8 studies), respectively (Figure 4).…”

“…So far, the impact of BCR-ABL transcript type on outcome in CML patients has been investigated in few studies but was inconclusive in the TKI era. In three studies, no significant difference in major molecular response (MMR) was found between different transcripts (9)(10)(11), whereas seven studies found that superior MMR was observed in patients with e14a2 transcripts (12)(13)(14)(15)(16)(17)(18). Six studies reported that e14a2 was a better predictor of deep molecular response (DMR) (10,12,13,15,16,18).…”

“…Six studies reported that e14a2 was a better predictor of deep molecular response (DMR) (10,12,13,15,16,18). However, Mulas et al (19) and Marce et al (11) showed that the transcript types did not affect DMR. In addition to molecular response, survival was also a major subject of debate.…”

“…Progression-free survival (PFS) was demonstrated to be the same in three studies (11,12,19), but to be significantly better in e14a2 patients in two studies (13,15). Overall survival (OS) was demonstrated to be the same in seven studies (12,13,16,(19)(20)(21)(22), but to be significantly different in two (11,15). To our knowledge, no meta-analysis has been conducted to summarize the conflicting evidence.…”

Discontinuation of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia: a Review of the Biological Factors Associated with Treatment-Free Remission

“…Studies have long reported a superior outcome for patients expressing the e14a2 transcript compared to those expressing the e13a2 transcript, including a deeper and more rapid molecular response as well as superior progression-free and overall survival [42][43][44]. Moreover, some studies have suggested that patients expressing e14a2 transcripts have a higher probability of achieving TFR than those expressing e13a2 [45, 46••], although others have failed to observe statistically significant differences [47].…”