The impact of BCR‐ABL1 transcript type on tyrosine kinase inhibitor responses and outcomes in patients with chronic myeloid leukemia

Abstract

Although the majority of patients with chronic myeloid leukemia do well with treatment with tyrosine kinase inhibitors (TKIs), some patients still have inferior outcomes. There are many factors that might play a part, including the different BCR-ABL1 transcript types at baseline. The current study was performed to determine the possible impact of different transcripts on the treatment responses and outcomes of patients with chronic myeloid leukemia who are receiving TKI therapy. The authors performed a systematic literature search by using the terms "b2a2/b3a2," "e13a2/e14a2," or "transcript type." e14a2 was the more common transcript type. The majority of the studies demonstrated no significant difference regarding age, sex, leukocyte counts, and hemoglobin levels between patients with the e13a2 and e14a2 transcripts. However, in approximately one-half of the studies, the e14a2 transcript was associated with higher platelet counts. Almost no studies demonstrated a significant association between disease risk scores and transcript types. In the majority of studies, having the e14a2 transcript was associated with earlier, deeper, and higher molecular response rates. Although better event-free survival was observed in patients with the e14a2 transcript in some of the studies, the majority demonstrated that transcript type did not have an impact on progression-free and overall survival. Treatment-free remission currently is a topic of much interest, and to the authors' knowledge there are limited data with conflicting results regarding the possible effects of transcript types on the outcomes of patients after discontinuation of TKIs. Because having the e14a2 transcript appears to be related to a favorable outcome, choosing second-generation TKIs for frontline therapy might be a convenient approach in patients with chronic myeloid leukemia with the e13a2 transcript. The authors believe this finding warrants further investigation.

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

“…The presence of e14a2 at baseline was associated with higher molecular response rates to imatinib. [17][18][19][20] While some studies have demonstrated a trend toward better survival outcomes with e14a2 transcript, 18,19 in other studies the type of transcript did not have any significant impact on long-term survival outcomes. 17,21 There are very limited data regarding the impact of these transcripts on response to second-generation TKI therapy.…”

Favorable outcome of chronic myeloid leukemia co‐expressing e13a2 and e14a2 transcripts, treated with nilotinib

“…Previous studies suggested that imatinib treatment was associated with a DMR and a favorable outcome in patients that expressed the e14a2 transcript. 5 These results were confirmed by a study with imatinib or second-generation TKI used frontline, showing that the achievement of a stable DMR was 63.8% in e14a2 expressing group compared with 36.2% in the e13a2 group. 6 Preliminary data involving a large cohort of CML patients treated with nilotinib in several clinical trials, showed no significant differences in PFS (88% vs 93%) and OS (89% vs 94%) between the e13a2 and e14a2 groups.…”

Therapy‐related chronic myeloid leukemia in a patient receiving peptide receptor radionuclide therapy for pancreatic neuroendocrine tumor

“…4,6 Similarly, in the TKI era, response to TKI treatment is excellent in patients with TR-CML in chronic phase. 6,11 Iriyama et al 6 have investigated the prognosis of 297 de novo CML and 11 TR-CML patients with a median follow-up of 48 months. Primary malignancy was solid tumor in 10 patients, while it was acute lymphoblastic leukemia in one patient.…”