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Nilotinib for CML With Co-expression of e13a2 and e14a2 Transcripts

By: Julia Fiederlein
Posted: Thursday, September 10, 2020

Patients with chronic myeloid leukemia (CML) who have co-expressing e13a2 and e14a2 transcripts seem to experience favorable outcomes after treatment with the tyrosine kinase inhibitor nilotinib, according to a study published in Hematological Oncology. However, Giovanni Caocci, MD, of the Businco Hospital, Cagliari, Italy, and colleagues explained that treatment options for this CML subgroup must be further investigated.

“In 90% of cases, mRNA splicing gives rise to major BCR-ABL1 transcripts with e13a2 or e14a2 junctions,” the investigators commented. “Both transcripts result in the expression of a 210-kDa BCR-ABL1 protein with a constitutively activated tyrosine kinase activity.”

A total of 183 patients with chronic-phase CML were treated in the front-line setting with 300 mg of nilotinib twice daily. Among this patient population, 28% expressed e13a2, 59% expressed e14a2, and 14% expressed both transcripts. One-step reverse transcription and quantitative real-time polymerase chain reaction assays were used to evaluate molecular responses. The investigators defined a molecular response of at least 4 as a deep molecular response and a molecular response of 3 as a major molecular response.

Overall, patients co-expressing both transcripts appeared to have a significantly higher incidence of deep molecular responses (100%) than those carrying the e14a2 (80.3%) or the e13a2 (80.7%) transcript alone (P = .037); this also seemed to be true at 6 (P = .033) and 12 (P = .04) months. The favorable outcome was maintained among the 115 patients with a molecular response of 4.5 (83.3% vs. 59.7%; P = .026). According to the multivariate analysis, only those co-expressing both transcripts had a significant chance of experiencing a deep molecular response (P = .008). The 60-month overall and progression-free survival rates were 98.8% and 97.8%, respectively. The duration of overall and progression-free survival did not seem to significantly differ between the three groups.

Disclosure: The study authors reported no conflicts of interest.



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