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Achievement of Treatment-Free Remission in CML Influenced by Transcript Variant

By: Sarah Campen, PharmD
Posted: Tuesday, February 19, 2019

For patients with chronic myeloid leukemia (CML), discontinuing treatment with tyrosine kinase inhibitors (TKIs) has become a realistic goal. However, researchers in Italy have discovered that patients with the e13a2 BCR-ABL transcript variant may be significantly less likely to achieve treatment-free remission than patients with the e14a2 variant. The results of their research were published in Cancer.

“The current data support the hypothesis that the e13a2 BCR-ABL transcript confers decreased sensitivity to treatment with TKI inhibitors, significantly reducing the possibility of achieving a [deep molecular response] and of maintaining it for more than 2 years,” stated Mariella D’Adda, MD, of the Local Social Health Authority (ASST) Spedali Civili Brescia, Brescia, Italy, and colleagues, “ultimately compromising the goal of achieving a [treatment-free remission].”

In this retrospective study of 173 patients, 67 (38.7%) had the e13a2 transcript and 106 patients (61.3%) had the e14a2 transcript. The achievement of both a deep molecular response (P = .008) and a sustained deep molecular response (P = .004) was favored significantly in those with the e14a2 transcript. After a median of 68 months, the sustained deep molecular response rate was 39.6% in patients with the e14a2 transcript compared with 19.4% in those with the e13a2 transcript.

Transcript type also seemed to influence maintenance of treatment-free remission (P = .005), as just 2 patients (3%) with the e13a2 transcript achieved a durable treatment-free remission compared with 25 patients (23.5%) with the e14a2 transcript. Based on these results, the authors concluded that the transcript type “should be added to the list of prognostic factors that have been associated with a higher risk of [treatment-free remission] failure.”

Disclosure: The study authors’ disclosure information may be found at wiley.com.



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