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

• Published in: Cancer 2018-10, Vol.124 (19), p.3806-3818
• Main Authors: Ercaliskan, Abdulkadir, Eskazan, A. Emre
• Format: Article
• Language: English
• Subjects: BCR‐ABL1; Chronic myeloid leukemia; chronic myeloid leukemia (CML); e13a2; e14a2; Enzyme inhibitors; Health risks; Hemoglobin; Leukemia; Leukocytes; Myeloid leukemia; Oncology; Patients; Remission; response; Survival; Therapy; Transcription; Tyrosine; tyrosine kinase inhibitor (TKI); Tyrosine kinase inhibitors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.31408

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. BCR‐ABL1 transcript types might play a role in patient responses and outcomes to tyrosine kinase inhibitors, and the e14a2 transcript generally appears to be associated with favorable outcomes. Prospective and randomized controlled trials with larger sample sizes still are needed to clarify the impact of transcript type on the short‐term and long‐term outcomes in patients with chronic myeloid leukemia receiving therapy with tyrosine kinase inhibitors.